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OXADIAZOLE COMPOUNDS

20200140400 ยท 2020-05-07

Assignee

Inventors

Cpc classification

International classification

Abstract

The present invention relates to a compound of formula (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein R.sup.1, R.sup.2, R.sup.3, L.sup.1, L.sup.2, L.sup.3, L.sup.4, L.sup.5 and n, have the same meaning as that defined in the claims and the description. The present invention also relates to compositions, in particular pharmaceuticals, comprising such compounds, and to uses of such compounds and compositions for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases, an protein misfolding disorders.

##STR00001##

Claims

1. A compound of formula (I) or (II); or a stereoisomer, enantiomer, racemic, or tautomer thereof, ##STR00362## wherein, n is an integer selected from 0, 1, 2 or 3; R.sup.1 is selected from the group consisting of C.sub.1-6 alkyl, halo, haloC.sub.1-6 alkyl, and haloC.sub.1-6alkyloxy; R.sup.2 is selected from the group consisting of C.sub.6-12 aryl, hydrogen, C.sub.1-6 alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6 alkyl, haloC.sub.1-6 alkyloxy, amino, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.1; R.sup.3 is selected from the group consisting of C.sub.6-12 aryl, hydrogen, C.sub.1-6 alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6 alkyl, haloC.sub.1-6 alkyloxy, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12 aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12 arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.2; L.sup.1 is a single bond, or is a group of formula (i); ##STR00363## wherein the left side of the group of formula (i) is attached to R.sup.2 and the right side thereof is attached to the oxadiazole ring; and wherein, m is an integer selected from 0, 1, 2, 3 or 4; p is an integer selected from 0, 1, 2, 3 or 4; L.sup.4 is a single bond, or is selected from the group consisting of O, and NR.sup.8; R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; or R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; R.sup.8 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, PO.sub.4, PO.sub.3, and (CR.sup.9R.sup.10).sub.q; wherein, q is an integer selected from 1, 2 or 3; R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; or R.sup.9 and R.sup.10together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; L.sup.3 is a single bond or is selected from the group consisting of (CR.sup.11R.sup.12).sub.r, O, and NR.sup.13; wherein, r is an integer selected from 1, 2 or 3; R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; or R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; R.sup.13 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; wherein at least one of L.sup.2, L.sup.3 is not a single bond; L.sup.5 is a single bond or CO; each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.6-12 aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6 alkyl, can be unsubstituted or substituted with one or more Z.sup.1; and wherein at least one carbon atom or heteroatom of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12 aryl, C.sub.3-8cycloalkyl, C.sub.6-12 arylC.sub.1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6 alkyl, or cyanoC.sub.1-6 alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6 alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; and wherein at least one carbon atom or heteroatom of said C.sub.1-6 alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6 alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6 alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6 alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6 alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6 alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; or wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-, 6-, or 7-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12 aryl, C.sub.3-8cycloalkyl, C.sub.6-12 arylC.sub.1-6 alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6 alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6 alkyl, C.sub.2-6alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6 alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2, each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12 arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6 alkylene*, and heteroaryleneC.sub.1-6 alkylene*; wherein * represents where R.sup.21 is bound to CO; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6 alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6 alkylene, or heteroaryleneC.sub.1-6 alkylene can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6 alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, S(O)R.sup.19, S(O).sub.2R.sup.19, SO.sub.2NR.sup.17R.sup.18, nitro, NR.sup.20C(O)R.sup.19, R.sup.21C(O)NR.sup.17R.sup.18, NR.sup.20S(O).sub.2R.sup.19, and NR.sup.20C(O)NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6 alkyl, C.sub.3-8cycloalkyl, C.sub.6-12 aryl, C.sub.1-6 alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6 alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6 alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, S(O)R.sup.19, S(O).sub.2R.sup.19, SO.sub.2NR.sup.17R.sup.18, nitro, NR.sup.20C(O)R.sup.19, R.sup.21C(O)NR.sup.17R.sup.18, NR.sup.20S(O).sub.2R.sup.19, and NR.sup.20C(O)NR.sup.17R.sup.18; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6 alkyl, C.sub.3-8cycloalkyl, C.sub.6-12 aryl, C.sub.1-6 alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; and with the proviso that for a compound of formula (I) when R.sup.2 is C.sub.6-12 aryl; L.sup.3 is a single bond, (CR.sup.11R.sup.12).sub.r, O, or NR.sup.13; then R.sup.3 is not hydrogen, C.sub.1-6alkyl, hydroxyl, or OR.sup.15; and with the proviso that for a compound of formula (I) when L.sup.1 is a single bond, R.sup.2 is not hydrogen; and with the proviso that said compound is not 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-(2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole; or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof.

2. The compound according to claim 1, having structural formula (IA) or (IIA), ##STR00364## wherein L.sup.1, L.sup.3, L.sup.5, n, R.sup.1, R.sup.2 and R.sup.3 have the same meaning as that defined in claim 1.

3. The compound according to claim 1, having structural formula (IB) or (IIB), ##STR00365## wherein, L.sup.1, n, R.sup.1, R.sup.2 and R.sup.3 have the same meaning as that defined in claim 1.

4. The compound according to claim 1, having structural formula (IC) or (IIC), ##STR00366## wherein, L.sup.3, n, R.sup.1, R.sup.2 and R.sup.3 have the same meaning as defined in claim 1.

5. The compound according to claim 1, having structural formula (ID) or (IID), ##STR00367## wherein, L.sup.3, n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5, have the same meaning as defined in claim 1.

6. The compound according to claim 1, having structural formula (IE) or (IIE), ##STR00368## wherein, L.sup.1, L.sup.2, L.sup.3, L.sup.5, n, R.sup.1, R.sup.2, R.sup.3, and Z.sup.1 have the same meaning as that defined in claim 1; and wherein, w is an integer selected from 1, 2, or 3.

7. The compound according to claim 1, having structural formula (IF) or (IIF), ##STR00369## wherein, L.sup.1, L.sup.3, L.sup.5, n, R.sup.1, R.sup.3, and Z.sup.1 have the same meaning as that defined in claim 1; and wherein w is an integer selected from 1, 2, or 3.

8. The compound according to claim 1, having structural formula (IG) or (IIG), ##STR00370## wherein, L.sup.2, L.sup.3, L.sup.5, n, R.sup.1, R.sup.3, R.sup.4, R.sup.5, and Z.sup.1 have the same meaning as defined in claim 1, and wherein, w is an integer selected from 1, 2, or 3.

9. The compound according to claim 1, having structural formula (IH) or (IIH), ##STR00371## wherein, L.sup.3, L.sup.5, n, R.sup.1, R.sup.3, R.sup.4, R.sup.5, and Z.sup.1 and w have the same meaning as defined in claim 1, and wherein, w is an integer selected from 1, 2, or 3.

10. The compound according to claim 1, wherein n is 0.

11. A compound selected from the group consisting of 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 4-(2-(4-(3-Phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 5-(4-Isopentylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorobenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-(Oxazol-5-yl)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 3-(p-Tolyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Fluorophenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-Isopropylphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 3-(p-Tolyl)-5-(4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(4-((4-(3-(p-Tolyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenyl)pyrrolidin-2-one; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(4-chlorophenyl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; 3-(3-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; 2-((4-(3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; 3-(3-Fluorophenyl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; 3-(3-Fluorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-(3-Fluorophenyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,4-difluorophenyl)-1,2,4-oxadiazole; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-Benzo[1,3]dioxol-5-ylmethyl-4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(2-methyl-benzyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-((4-(3-Benzyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-((S)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Methoxy-benzenesulfonyl)-4[3-((R)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-Benzo[1,3]dioxol-5-ylmethyl-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-((4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(4-chloro-phenyl)-ethyl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; 3-(4-Chlorobenzyl)-5-(4-(2-fluorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(2-Chloro-benzyl)-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methyl-benzyl)-piperazine; 4-{4-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-butyronitrile; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-ethoxy-ethyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-propyl-piperazine; 3-(4-Chlorobenzyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4,4,4-trifluoro-butyl)-piperazine; 3-(4-Chlorobenzyl)-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-(4-Chlorobenzyl)-5-(4-isopropylpiperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-{4-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-3H-benzooxazol-2-one; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-dimethylpiperazine-1-sulfonamide; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-diethylpiperazine-1-sulfonamide; 4-((4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)morpholine; 3-(3-Chlorobenzyl)-5-(4-(pyrrolidin-1-ylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(Azepan-1-ylsulfonyl)piperazin-1-yl)-3-(3-chlorobenzyl)-1,2,4-oxadiazole; 3-(3-Chlorobenzyl)-5-(4-((4-methoxypiperidin-1-yl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Fluoro-benzenesulfonyl)-4[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; N-(4-{4-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-phenyl)-acetamide; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-methyl-benzyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-isopropoxy-benzenesulfonyl)-piperazine; 3-(4-((4-(3-(3-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenoxy)propanenitrile; 1-(2,3-Dihydro-benzofuran-5-sulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-(3-Fluorobenzyl)-5-(4-((4-isopropoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(4-Chloro-benzyl)-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl][1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-(4-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 1-(4-Methylsulfanyl-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 4-(2-(4-(3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 5-(4-Isopentylpiperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(difluoro(4-fluorophenyl)methyl)-1,2,4-oxadiazole; 3-(Difluoro(4-fluorophenyl)methyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-(Cyclopropylmethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-Ethoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(2-methyl-pyridin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-((2-methylpyridin-4-yl)methyl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 2-((4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; 5-(4-Isopentylpiperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 4-(2-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 4-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)butanenitrile; 5-(4-((6-Methylpyridin-2-yl)methyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-chlorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-chlorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclopropyl-5-(4-(4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclopropyl-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2-(2-methylpyridin-4-yl)propan-2-yl)-1,2,4-oxadiazole; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; (5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol; 3-(Methoxymethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((4-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((3-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(phenoxymethyl)-1,2,4-oxadiazole; 3-((Cyclopropylmethoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-((pyridin-3-yloxy)methyl)-1,2,4-oxadiazole; 4-((5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methoxy)benzonitrile; 3-((4-Fluorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-propyl-1,2,4-oxadiazole; 3-Butyl-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Tert-butyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclohexyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Isopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-Methoxyethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; 5-(7-((4-Methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-(Methylthio)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-Ethoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-(Difluoromethoxy)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; (3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methanone; 3-(4-Fluorobenzyl)-5-(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; 3-(2-Methoxyethyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; and a solvate, hydrate, pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising one or more pharmaceutically excipients and a therapeutically effective amount of a compound according to claim 1; or a therapeutically effective amount of a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof.

13. A compound according to claim 1 or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof for use as a medicament.

14. A compound according to claim 1, or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole, 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof for use as a medicine for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases; and/or protein misfolding disorders.

15. A compound according to claim 1, or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-S-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition thereof for use as a medicine for the prevention and/or treatment of diabetes mellitus, Parkinson's disease, Alzheimer's disease, diffuse Lewy body disease, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy, Huntington's disease, frontotemporal lobar degeneration (FTLD), multiple system atrophy, cystic fibrosis, Creutzfeld-Jacob's disease, impaired glucose tolerance, hyperglycemia, hypoglycemia, glyceraldehyde-3-phosphate dehydrogenase deficiency, hyperinsulinism, impaired insulin production, impaired insulin sensitivity, metabolic syndrome, insulin resistance syndrome, obesity, lipidoses, cardiac lipidoses, dyslipidemia, fatty liver, lipodistrophy, cardiovascular diseases and hypertension.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0115] FIG. 1 represents in Section (A) a graph plotting the non-fasted body weight of db/db mice treated with compound 110 (Cmpd 110) of the invention, as a function of duration of treatment in weeks. Section (B) is a graph plotting the blood glucose levels of fasted db/db mice treated with compound Cmpd 110 of the invention, as a function of duration of treatment in weeks. Section (C) is a graph plotting the plasma insulin levels of db/db mice treated with compound Cmpd 110 of the invention, as a function of duration of treatment in weeks.

DETAILED DESCRIPTION OF THE INVENTION

[0116] Before the present invention is described, it is to be understood that this invention is not limited to particular processes, methods, and compounds described, as such processes, methods, and compounds may, of course, vary. It is also to be understood that the terminology used herein is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.

[0117] When describing the compounds and processes of the invention, the terms used are to be construed in accordance with the following definitions, unless a context dictates otherwise.

[0118] As used in the specification and the appended claims, the singular forms a, all, and the include both singular and plural referents unless the context clearly dictates otherwise. By way of example, a compound means one compound or more than one compound.

[0119] The terms comprising, comprises and comprised of as used herein are synonymous with including, includes or containing, contains, and are inclusive or open-ended and do not exclude additional, non-recited members, elements or method steps. The terms comprising, comprises and comprised of also include the term consisting of.

[0120] The term about as used herein when referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/10% or less, preferably +/5% or less, more preferably +/1% or less, and still more preferably +/0.1% or less of and from the specified value, insofar such variations are appropriate to perform in the disclosed invention. It is to be understood that the value to which the modifier about refers is itself also specifically, and preferably, disclosed.

[0121] As used herein, the term and/or, when used in a list of two or more items, means that any one of the listed items can be employed by itself or any combination of two or more of the listed items can be employed. For example, if a list is described as comprising group A, B, and/or C, the list can comprise A alone; B alone; C alone; A and B in combination; A and C in combination, B and C in combination; or A, B, and C in combination.

[0122] The recitation of numerical ranges by endpoints includes all integer numbers and, where appropriate, fractions subsumed within that range (e.g. 1 to 5 can include 1, 2, 3, 4 when referring to, for example, a number of elements, and can also include 1.5, 2, 2.75 and 3.80, when referring to, for example, measurements). The recitation of end points also includes the end point values themselves (e.g. from 1.0 to 5.0 includes both 1.0 and 5.0). Any numerical range recited herein is intended to include all sub-ranges subsumed therein.

[0123] Reference throughout this specification to one embodiment or an embodiment means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases in one embodiment or in an embodiment in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to a person skilled in the art from this disclosure, in one or more embodiments. Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.

[0124] Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, definitions for the terms used in the description are included to better appreciate the teaching of the present invention.

[0125] When describing the present invention, the terms used are to be construed in accordance with the following definitions, unless a context dictates otherwise.

[0126] The terms described above and others used in the specification are well understood to those in the art.

[0127] Whenever the term substituted is used herein, it is meant to indicate that one or more hydrogen atoms on the atom indicated in the expression using substituted is replaced with a selection from the indicated group, provided that the indicated atom's normal valence is not exceeded, and that the substitution results in a chemically stable compound, i.e. a compound that is sufficiently robust to survive isolation from a reaction mixture.

[0128] Where groups can be substituted, such groups may be substituted with one or more, and preferably one, two or three substituents. Preferred substituents may be selected from but not limited to, for example, the group comprising halo, hydroxyl, C.sub.1-6alkyl, C.sub.1-6alkoxy, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, cyano, amino, nitro, carboxyl, aminocarbonyl, hydroxycarbonylC.sub.1-6alkyl, C.sub.1-6alkyloxycarbonyl, mono- or diC.sub.1-6alkylamino, mono- or diC.sub.1-6alkylaminocarbonyl, C.sub.1-6alkylcarbonyl, S(O)C.sub.1-6alkyl, S(O).sub.2C.sub.1-6alkyl, C.sub.1-6alkylcarbonylamino, and mono or di-C.sub.1-6alkylaminocarbonylC.sub.1-6alkyl.

[0129] The terminology regarding a chemical group wherein at least one carbon atom or heteroatom of said group can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2 as used herein, refers to a group where two or more hydrogen atoms on a carbon atom or heteroatom of said group are taken together to form CO, CS, NO, NS, SO or S(O).sub.2. As an example, the terminology an alkyl wherein a carbon atom or heteroatom of said alkyl can oxidized to form a CO, CS, NO, NS, SO or S(O).sub.2, includes among other examples CH.sub.3C(O)CH.sub.2, CH.sub.3C(O), CH.sub.3C(S)CH.sub.2 and (CH.sub.3).sub.2CH.sub.2C(O)CH.sub.2CH.sub.2. For example, the terminology a 5-, 6-, or 7-membered heterocyclyl wherein a carbon atom or heteroatom of said heterocyclyl can be oxidized to form a CO, CS, NO, NS, SO or S(O).sub.2, includes among other examples 6-oxo-1H-pyridin-3-yl, 2-oxo-1H-pyridin-4yl, 6-thioxo-1H-pyridin-3-yl and 2-thioxo-1H-pyridin-4yl.

[0130] The term halo or halogen as a group or part of a group is generic for fluoro, chloro, bromo, iodo.

[0131] The term amino refers to the group NH.sub.2.

[0132] The term hydroxyl or hydroxy as used herein refers to the group OH.

[0133] The term thiol or sulfuhydryl refers to the group SH.

[0134] The term oxo as used herein refers to the group O.

[0135] The term nitro as used herein refers to the group NO.sub.2.

[0136] The term cyano as used herein refers to the group CN.

[0137] The term carboxy or carboxyl or hydroxycarbonyl as used herein refers to the group CO.sub.2H.

[0138] The term aminocarbonyl as used herein refers to the group CONH.sub.2.

[0139] The term alkyl by itself or as part of another substituent refers to a hydrocarbyl group of formula C.sub.nH.sub.2n+1 wherein n is a number greater than or equal to 1. Alkyl groups may be linear or branched and may be substituted as indicated herein. Generally, alkyl groups of this invention comprise from 1 to 6 carbon atoms, preferably from 1 to 5 carbon atoms, preferably from 1 to 4 carbon atoms, more preferably from 1 to 3 carbon atoms, still more preferably 1 to 2 carbon atoms. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term C.sub.1-6alkyl, as a group or part of a group, refers to a hydrocarbyl group of formula C.sub.nH.sub.2n+1 wherein n is a number ranging from 1 to 6. Thus, for example, C.sub.1-6alkyl includes all linear or branched alkyl groups with between 1 and 6 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers, hexyl and its isomers. For example, C.sub.1-5alkyl includes all includes all linear or branched alkyl groups with between 1 and 5 carbon atoms, and thus includes methyl, ethyl, n-propyl, i-propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t-butyl); pentyl and its isomers. For example, C.sub.1-4alkyl includes all linear or branched alkyl groups with between 1 and 4 carbon atoms, and thus includes methyl, ethyl, n-propyl, propyl, butyl and its isomers (e.g. n-butyl, i-butyl and t-butyl). For example C.sub.1-3alkyl includes all linear or branched alkyl groups with between 1 and 3 carbon atoms, and thus includes methyl, ethyl, n-propyl, propyl. A substituted C.sub.1-6alkyl refers to a C.sub.1-6alkyl group substituted with one or more substituent(s) (for example 1 to 3 substituent(s), for example 1, 2, or 3 substituent(s)) at any available point of attachment.

[0140] When the suffix ene is used in conjunction with an alkyl group, i.e. alkylene, this is intended to mean the alkyl group as defined herein having two single bonds as points of attachment to other groups. As used herein, the term C.sub.1-6alkylene, by itself or as part of another substituent, refers to C.sub.1-6alkyl groups that are divalent, i.e., with two single bonds for attachment to two other groups. Alkylene groups may be linear or branched and may be substituted as indicated herein. Non-limiting examples of alkylene groups include methylene (CH.sub.2), ethylene (CH.sub.2CH.sub.2), methylmethylene (CH(CH.sub.3)), 1-methyl-ethylene (CH(CH.sub.3)CH.sub.2), n-propylene (CH.sub.2CH.sub.2CH.sub.2), 2-methylpropylene (CH.sub.2CH(CH.sub.3)CH.sub.2), 3-methylpropylene (CH.sub.2CH.sub.2CH(CH.sub.3)), n-butylene (CH.sub.2CH.sub.2CH.sub.2CH.sub.2), 2-methylbutylene (CH.sub.2CH(CH.sub.3)CH.sub.2CH.sub.2), 4-methylbutylene (CH.sub.2CH.sub.2CH.sub.2CH(CH.sub.3)), pentylene and its chain isomers, hexylene and its chain isomers.

[0141] When the term alkyl is used as a suffix following another term, as in hydroxyalkyl, this is intended to refer to an alkyl group, as defined above, being substituted with one or two (preferably one) substituent(s) selected from the other, specifically-named group, also as defined herein. The term hydroxyC.sub.1-6alkyl therefore refers to a R.sup.aOH group wherein R.sup.a is C.sub.1-6alkylene as defined herein.

[0142] The term haloC.sub.1-6alkyl as a group or part of a group, refers to a C.sub.1-6alkyl group having the meaning as defined above wherein one, two, or three hydrogen atoms are each replaced with a halogen as defined herein. Non-limiting examples of such haloC.sub.1-6alkyl groups include chloromethyl, 1-bromoethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1,1-trifluoroethyl, trichloromethyl, tribromomethyl, and the like.

[0143] The term trihalomethyl as a group or part of a group, refers to a C.sub.1 alkyl group (methyl) having the meaning as defined above wherein three hydrogen atoms are each replaced with a halogen as defined herein. Non-limiting examples of such trihalomethyl groups include trichloromethyl, tribromomethyl, and the like.

[0144] The term C.sub.1-6alkoxy or C.sub.1-6alkyloxy, as a group or part of a group, refers to a group having the formula OR.sup.b wherein R.sup.b is C.sub.1-6alkyl as defined herein above. Non-limiting examples of suitable C.sub.1-6alkoxy include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy and hexyloxy.

[0145] The term haloC.sub.1-6alkoxy, as a group or part of a group, refers to a group of formula OR.sup.c wherein R.sup.c is haloC.sub.1-6alkyl as defined herein. Non-limiting examples of suitable haloC.sub.1-6alkoxy include fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy, 2,2,2-trichloro ethoxy, trichloromethoxy, 2-bromoethoxy, pentafluoroethyl, 3,3,3-trichloropropoxy, 4,4,4-trichlorobutoxy.

[0146] The term alkenyl as a group or part of a group, refers to an unsaturated hydrocarbyl group, which may be linear, or branched, comprising one or more carbon-carbon double bonds. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term C.sub.2-6alkenyl refers to an unsaturated hydrocarbyl group, which may be linear, or branched comprising one or more carbon-carbon double bonds and comprising from 2 to 6 carbon atoms. For example, C.sub.2-4alkenyl includes all linear, or branched alkenyl groups having 2 to 4 carbon atoms. Examples of C.sub.2-6alkenyl groups are ethenyl, 2-propenyl, 2-butenyl, 3-butenyl, 2-pentenyl and its isomers, 2-hexenyl and its isomers, 2,4-pentadienyl. and the like.

[0147] Where alkenyl groups as defined herein are divalent groups having single bonds for attachment to two other groups, they are termed alkenylene. As used herein, the term C.sub.2-6alkenylene, by itself or as part of another substituent, refers to C.sub.2-6alkenyl groups that are divalent, i.e., with two single bonds for attachment to two other groups.

[0148] The term C.sub.2-6alkenyloxy, as a group or part of a group, refers to a group having the formula OR.sup.d wherein R.sup.d is C.sub.2-6alkenyl as defined herein above.

[0149] The term alkynyl by itself or as part of another substituent, refers to an unsaturated hydrocarbyl group, which may be linear, or branched, comprising one or more carbon-carbon triple bonds. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term C.sub.2-6alkynyl refers to an unsaturated hydrocarbyl group, which may be linear, or branched comprising one or more carbon-carbon triple bonds and comprising from 2 to 6 carbon atoms. For example, C.sub.2-4alkynyl includes all linear, or branched alkynyl groups having 2 to 4 carbon atoms. Non limiting examples of C.sub.2-6alkynyl groups include ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 2-pentynyl and its chain isomers, 2-hexynyl and its chain isomers, and the like.

[0150] Where alkynyl groups as defined herein are divalent groups having single bonds for attachment to two other groups, they are termed alkynylene. As used herein, the term C.sub.2-6alkynylene, by itself or as part of another substituent, refers to C.sub.2-6alkynyl groups that are divalent, i.e., with two single bonds for attachment to two other groups.

[0151] The term C.sub.2-6alkynyloxy, as a group or part of a group, refers to a group having the formula OR.sup.e wherein R.sup.e is C.sub.2-6alkynyl as defined herein above.

[0152] The term cycloalkyl, as a group or part of a group, refers to a cyclic alkyl group, that is a monovalent, saturated, hydrocarbyl group having 1 or more cyclic structure, and comprising from 3 to 12 carbon atoms, more preferably from 3 to 9 carbon atoms, more preferably from 3 to 7 carbon atoms; more preferably from 3 to 6 carbon atoms. Cycloalkyl includes all saturated hydrocarbon groups containing 1 or more rings, including monocyclic or bicyclic groups. The further rings of multi-ring cycloalkyls may be either fused, bridged and/or joined through one or more spiro atoms. When a subscript is used herein following a carbon atom, the subscript refers to the number of carbon atoms that the named group may contain. For example, the term C.sub.3-8cycloalkyl, a cyclic alkyl group comprising from 3 to 8 carbon atoms. For example, the term C.sub.3-6cycloalkyl, a cyclic alkyl group comprising from 3 to 6 carbon atoms. Examples of C.sub.3-12cycloalkyl groups include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicycle[2.2.1]heptan-2yl, (1S,4R)-norbornan-2-yl, (1R,4R)-norbornan-2-yl, (1S,4S)-norbornan-2-yl, (1R,4S)-norbornan-2-yl.

[0153] When the suffix ene is used in conjunction with a cycloalkyl group, i.e. cycloalkylene, this is intended to mean the cycloalkyl group as defined herein having two single bonds as points of attachment to other groups. Non-limiting examples of C.sub.3-8cycloalkylene include 1,2-cyclopropylene, 1,1-cyclopropylene, 1,1-cyclobutylene, 1,2-cyclobutylene, 1,3-cyclopentylene, 1,1-cyclopentylene, and 1,4-cyclohexylene.

[0154] Where an alkylene or cycloalkylene group is present, connectivity to the molecular structure of which it forms part may be through a common carbon atom or different carbon atom. To illustrate this applying the asterisk nomenclature of this invention, a C.sub.3alkylene group may be for example *CH.sub.2CH.sub.2CH.sub.2*, *CH(CH.sub.2CH.sub.3)* or *CH.sub.2CH(CH.sub.3)*. Likewise a C.sub.3cycloalkylene group may be

##STR00004##

[0155] The term C.sub.6-12cycloalkyloxy, as a group or part of a group, refers to a group having the formula OR.sup.f wherein R.sup.f is C.sub.3-12cycloalkyl as defined herein above.

[0156] The term C.sub.6-12aryl, as a group or part of a group, refers to a polyunsaturated, aromatic hydrocarbyl group having a single ring (i.e. phenyl) or multiple aromatic rings fused together (e.g. naphthyl), or linked covalently, typically containing 6 to 12 atoms; preferably 6 to 10, wherein at least one ring is aromatic. The aromatic ring may optionally include one to two additional rings (either cycloalkyl, heterocyclyl or heteroaryl) fused thereto. Examples of suitable aryl include C.sub.6-10aryl, more preferably C.sub.6-8aryl. Non-limiting examples of C.sub.6-12aryl comprise phenyl, biphenylyl, biphenylenyl, or 1- or 2-naphthanelyl; 1-, 2-, 3-, 4-, 5- or 6-tetralinyl (also known as 1,2,3,4-tetrahydronaphtalene); 1-, 2-, 3-, 4-, 5-, 6-, 7- or 8-azulenyl, 4-, 5-, 6 or 7-indenyl; 4- or 5-indanyl; 5-, 6-, 7- or 8-tetrahydronaphthyl; 1,2,3,4-tetrahydronaphthyl; and 1,4-dihydronaphthyl; 1-, 2-, 3-, 4- or 5-pyrenyl. A substituted C.sub.6-12aryl refers to a C.sub.6-12aryl group having one or more substituent(s) (for example 1, 2 or 3 substituent(s), or 1 to 2 substituent(s)), at any available point of attachment.

[0157] As used herein, the term spiro atom refers to the atom that connects two cyclic structures in a spiro compound. Non limiting examples of Spiro atoms include quaternary carbon atoms. As used herein, the term Spiro compound refers to a bicyclic compound wherein the two rings are connected through one atom.

[0158] When the suffix ene is used in conjunction with an aryl group; i.e. arylene, this is intended to mean the aryl group as defined herein having two single bonds as points of attachment to other groups. Suitable C.sub.6-12arylene groups include 1,4-phenylene, 1,2-phenylene, 1,3-phenylene, biphenylylene, naphthylene, indenylene, 1-, 2-, 5- or 6-tetralinylene, and the like. Where a carbon atom in an aryl group is replaced with a heteroatom, the resultant ring is referred to herein as a heteroaryl ring.

[0159] The term C.sub.6-12aryloxy, as a group or part of a group, refers to a group having the formula OR.sup.g wherein R.sup.g is C.sub.6-12aryl as defined herein above.

[0160] The term C.sub.6-12arylC.sub.1-6alkyl, as a group or part of a group, means a C.sub.1-6alkyl as defined herein, wherein at least one hydrogen atom is replaced by at least one C.sub.6-12aryl as defined herein. Non-limiting examples of C.sub.6-12arylC.sub.1-6alkyl group include benzyl, phenethyl, dibenzylmethyl, methylphenylmethyl, 3-(2-naphthyl)-butyl, and the like.

[0161] The term C.sub.6-13arylC.sub.1-6alkylC.sub.6-12aryl, as a group or part of a group, means a C.sub.6-12aryl, wherein at least one hydrogen atom is replaced by at least one C.sub.6-12arylC.sub.1-6alkyl as defined herein.

[0162] The term C.sub.6-12aryleneC.sub.1-6alkylene, as a group or part of a group, refers to a group having the formula R.sup.hR.sup.a wherein R.sup.h is C.sub.6-12arylene as defined herein and R.sup.a is C.sub.1-6alkylene as defined herein.

[0163] The term C.sub.6-12arylC.sub.1-6alkyloxy, as a group or part of a group, refers to a group having the formula OR.sup.aR.sup.g wherein R.sup.g is C.sub.6-12aryl, and R.sup.a is C.sub.1-6alkylene as defined herein above.

[0164] The terms heterocyclyl or heterocycloalkyl or heterocyclo, as a group or part of a group, refer to non-aromatic, fully saturated or partially unsaturated cyclic groups (for example, 3 to 7 member monocyclic, 7 to 11 member bicyclic, or comprising a total of 3 to 10 ring atoms) which have at least one heteroatom in at least one carbon atom-containing ring; wherein said ring may be fused to an aryl, cycloalkyl, heteroaryl or heterocyclyl ring. Each ring of the heterocyclyl group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from N, O and/or S, where the N and S heteroatoms may optionally be oxidized and the N heteroatoms may optionally be quaternized, and wherein at least one carbon atom of heterocyclyl can be oxidized to form at least one CO. The heterocyclic group may be attached at any heteroatom or carbon atom of the ring or ring system, where valence allows. The rings of multi-ring heterocycles may be fused, bridged and/or joined through one or more Spiro atoms.

[0165] Non limiting exemplary heterocyclic groups include aziridinyl, oxiranyl, thiiranyl, piperidinyl, azetidinyl, oxetanyl, pyrrolidinyl, thietanyl, 2-imidazolinyl, pyrazolidinyl imidazolidinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, succinimidyl, 3H-indolyl, indolinyl, chromanyl (also known as 3,4-dihydrobenzo[b]pyranyl), isoindolinyl, 2H-pyrolyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, 4H-quinolizinyl, 2-oxopiperazinyl, piperazinyl, homopiperazinyl, 2-pyrazolinyl, 3-pyrazolinyl, tetrahydro-2H-pyranyl, 2H-pyranyl, 4H-pyranyl, 3,4-dihydro-2H-pyranyl, 3-dioxolanyl, 1,4-dioxanyl, 2,5-dioxoimidazolidinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, indolinyl, tetrahydropyranyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydroquinolinyl, tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, thiomorpholin-4-yl, thiomorpholin-4-ylsulfoxide, thiomorpholin-4-ylsulfone, 1,3-dioxolanyl, 1,4-oxathianyl, 1,4-dithianyl, 1,3,5-trioxanyl, 1H-pyrrolizinyl, tetrahydro-1,1-dioxothiophenyl, N-formylpiperazinyl, and morpholin-4-yl. The term aziridinyl as used herein includes aziridin-1-yl and aziridin-2-yl. The term oxyranyl as used herein includes oxyranyl-2-yl. The term thiiranyl as used herein includes thiiran-2-yl. The term azetidinyl as used herein includes azetidin-1-yl, azetidin-2-yl and azetidin-3-yl. The term oxetanyl as used herein includes oxetan-2-yl and oxetan-3-yl. The term thietanyl as used herein includes thietan-2-yl and thietan-3-yl. The term pyrrolidinyl as used herein includes pyrrolidin-1-yl, pyrrolidin-2-yl and pyrrolidin-3-yl. The term tetrahydrofuranyl as used herein includes tetrahydrofuran-2-yl and tetrahydrofuran-3-yl. The term tetrahydrothiophenyl as used herein includes tetrahydrothiophen-2-yl and tetrahydrothiophen-3-yl. The term succinimidyl as used herein includes succinimid-1-yl and succininmid-3-yl. The term dihydropyrrolyl as used herein includes 2,3-dihydropyrrol-1-yl, 2,3-dihydro-1H-pyrrol-2-yl, 2,3-dihydro-1H-pyrrol-3-yl, 2,5-dihydropyrrol-1-yl, 2,5-dihydro-1H-pyrrol-3-yl and 2,5-dihydropyrrol-5-yl. The term 2H-pyrrolyl as used herein includes 2H-pyrrol-2-yl, 2H-pyrrol-3-yl, 2H-pyrrol-4-yl and 2H-pyrrol-5-yl. The term 3H-pyrrolyl as used herein includes 3H-pyrrol-2-yl, 3H-pyrrol-3-yl, 3H-pyrrol-4-yl and 3H-pyrrol-5-yl. The term dihydrofuranyl as used herein includes 2,3-dihydrofuran-2-yl, 2,3-dihydrofuran-3-yl, 2,3-dihydrofuran-4-yl, 2,3-dihydrofuran-5-yl, 2,5-dihydrofuran-2-yl, 2,5-dihydrofuran-3-yl, 2,5-dihydrofuran-4-yl and 2,5-dihydrofuran-5-yl. The term dihydrothiophenyl as used herein includes 2,3-dihydrothiophen-2-yl, 2,3-dihydrothiophen-3-yl, 2,3-dihydrothiophen-4-yl, 2,3-dihydrothiophen-5-yl, 2,5-dihydrothiophen-2-yl, 2,5-dihydrothiophen-3-yl, 2,5-dihydrothiophen-4-yl and 2,5-dihydrothiophen-5-yl. The term imidazolidinyl as used herein includes imidazolidin-1-yl, imidazolidin-2-yl and imidazolidin-4-yl. The term pyrazolidinyl as used herein includes pyrazolidin-1-yl, pyrazolidin-3-yl and pyrazolidin-4-yl. The term imidazolinyl as used herein includes imidazolin-1-yl, imidazolin-2-yl, imidazolin-4-yl and imidazolin-5-yl. The term pyrazolinyl as used herein includes 1-pyrazolin-3-yl, 1-pyrazolin-4-yl, 2-pyrazolin-1-yl, 2-pyrazolin-3-yl, 2-pyrazolin-4-yl, 2-pyrazolin-5-yl, 3-pyrazolin-1-yl, 3-pyrazolin-2-yl, 3-pyrazolin-3-yl, 3-pyrazolin-4-yl and 3-pyrazolin-5-yl. The term dioxolanyl also known as 1,3-dioxolanyl as used herein includes dioxolan-2-yl, dioxolan-4-yl and dioxolan-5-yl. The term dioxolyl also known as 1,3-dioxolyl as used herein includes dioxol-2-yl, dioxol-4-yl and dioxol-5-yl. The term oxazolidinyl as used herein includes oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl and oxazolidin-5-yl. The term isoxazolidinyl as used herein includes isoxazolidin-2-yl, isoxazolidin-3-yl, isoxazolidin-4-yl and isoxazolidin-5-yl. The term oxazolinyl as used herein includes 2-oxazolinyl-2-yl, 2-oxazolinyl-4-yl, 2-oxazolinyl-5-yl, 3-oxazolinyl-2-yl, 3-oxazolinyl-4-yl, 3-oxazolinyl-5-yl, 4-oxazolinyl-2-yl, 4-oxazolinyl-3-yl, 4-oxazolinyl-4-yl and 4-oxazolinyl-5-yl. The term isoxazolinyl as used herein includes 2-isoxazolinyl-3-yl, 2-isoxazolinyl-4-yl, 2-isoxazolinyl-5-yl, 3-isoxazolinyl-3-yl, 3-isoxazolinyl-4-yl, 3-isoxazolinyl-5-yl, 4-isoxazolinyl-2-yl, 4-isoxazolinyl-3-yl, 4-isoxazolinyl-4-yl and 4-isoxazolinyl-5-yl. The term thiazolidinyl as used herein includes thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl and thiazolidin-5-yl. The term isothiazolidinyl as used herein includes isothiazolidin-2-yl, isothiazolidin-3-yl, isothiazolidin-4-yl and isothiazolidin-5-yl. The term chromanyl as used herein includes chroman-2-yl, chroman-3-yl, chroman-4-yl, chroman-5-yl, chroman-6-yl, chroman-7-yl and chroman-8-yl. The term thiazolinyl as used herein includes 2-thiazolinyl-2-yl, 2-thiazolinyl-4-yl, 2-thiazolinyl-5-yl, 3-thiazolinyl-2-yl, 3-thiazolinyl-4-yl, 3-thiazolinyl-5-yl, 4-thiazolinyl-2-yl, 4-thiazolinyl-3-yl, 4-thiazolinyl-4-yl and 4-thiazolinyl-5-yl. The term isothiazolinyl as used herein includes 2-isothiazolinyl-3-yl, 2-isothiazolinyl-4-yl, 2-isothiazolinyl-5-yl, 3-isothiazolinyl-3-yl, 3-isothiazolinyl-4-yl, 3-isothiazolinyl-5-yl, 4-isothiazolinyl-2-yl, 4-isothiazolinyl-3-yl, 4-isothiazolinyl-4-yl and 4-isothiazolinyl-5-yl. The term piperidyl also known as piperidinyl as used herein includes piperid-1-yl, piperid-2-yl, piperid-3-yl and piperid-4-yl. The term dihydropyridinyl as used herein includes 1,2-dihydropyridin-1-yl, 1,2-dihydropyridin-2-yl, 1,2-dihydropyridin-3-yl, 1,2-dihydropyridin-4-yl, 1,2-dihydropyridin-5-yl, 1,2-dihydropyridin-6-yl, 1,4-dihydropyridin-1-yl, 1,4-dihydropyridin-2-yl, 1,4-dihydropyridin-3-yl, 1,4-dihydropyridin-4-yl, 2,3-dihydropyridin-2-yl, 2,3-dihydropyridin-3-yl, 2,3-dihydropyridin-4-yl, 2,3-dihydropyridin-5-yl, 2,3-dihydropyridin-6-yl, 2,5-dihydropyridin-2-yl, 2,5-dihydropyridin-3-yl, 2,5-dihydropyridin-4-yl, 2,5-dihydropyridin-5-yl, 2,5-dihydropyridin-6-yl, 3,4-dihydropyridin-2-yl, 3,4-dihydropyridin-3-yl, 3,4-dihydropyridin-4-yl, 3,4-dihydropyridin-5-yl and 3,4-dihydropyridin-6-yl. The term tetrahydropyridinyl as used herein includes 1,2,3,4-tetrahydropyridin-1-yl, 1,2,3,4-tetrahydropyridin-2-yl, 1,2,3,4-tetrahydropyridin-3-yl, 1,2,3,4-tetrahydropyridin-4-yl, 1,2,3,4-tetrahydropyrid in-5-yl, 1,2,3,4-tetrahydropyridin-6-yl, 1,2,3,6-tetrahydropyridin-1-yl, 1,2,3,6-tetrahydropyridin-2-yl, 1,2,3,6-tetrahydropyridin-3-yl, 1,2,3,6-tetrahydropyridin-4-yl, 1,2,3,6-tetrahydropyridin-5-yl, 1,2,3,6-tetrahydropyridin-6-yl, 2,3,4,5-tetrahydropyridin-2-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-3-yl, 2,3,4,5-tetrahydropyridin-4-yl, 2,3,4,5-tetrahydropyridin-5-yl and 2,3,4,5-tetrahydropyridin-6-yl. The term tetrahydropyranyl also known as oxanyl or tetrahydro-2H-pyranyl, as used herein includes tetrahydropyran-2-yl, tetrahydropyran-3-yl and tetrahydropyran-4-yl. The term 2H-pyranyl as used herein includes 2H-pyran-2-yl, 2H-pyran-3-yl, 2H-pyran-4-yl, 2H-pyran-5-yl and 2H-pyran-6-yl. The term 4H-pyranyl as used herein includes 4H-pyran-2-yl, 4H-pyran-3-yl and 4H-pyran-4-yl. The term 3,4-dihydro-2H-pyranyl as used herein includes 3,4-dihydro-2H-pyran-2-yl, 3,4-dihydro-2H-pyran-3-yl, 3,4-dihydro-2H-pyran-4-yl, 3,4-dihydro-2H-pyran-5-yl and 3,4-dihydro-2H-pyran-6-yl. The term 3,6-dihydro-2H-pyranyl as used herein includes 3,6-dihydro-2H-pyran-2-yl, 3,6-dihydro-2H-pyran-3-yl, 3,6-dihydro-2H-pyran-4-yl, 3,6-dihydro-2H-pyran-5-yl and 3,6-dihydro-2H-pyran-6-yl. The term tetrahydrothiophenyl, as used herein includes tetrahydrothiophen-2-yl, tetrahydrothiophenyl-3-yl and tetrahydrothiophenyl-4-yl. The term 2H-thiopyranyl as used herein includes 2H-thiopyran-2-yl, 2H-thiopyran-3-yl, 2H-thiopyran-4-yl, 2H-thiopyran-5-yl and 2H-thiopyran-6-yl. The term 4H-thiopyranyl as used herein includes 4H-thiopyran-2-yl, 4H-thiopyran-3-yl and 4H-thiopyran-4-yl. The term 3,4-dihydro-2H-thiopyranyl as used herein includes 3,4-dihydro-2H-thiopyran-2-yl, 3,4-dihydro-2H-thiopyran-3-yl, 3,4-dihydro-2H-thiopyran-4-yl, 3,4-dihydro-2H-thiopyran-5-yl and 3,4-dihydro-2H-thiopyran-6-yl. The term 3,6-dihydro-2H-thiopyranyl as used herein includes 3,6-dihydro-2H-thiopyran-2-yl, 3,6-dihydro-2H-thiopyran-3-yl, 3,6-dihydro-2H-thiopyran-4-yl, 3,6-dihydro-2H-thiopyran-5-yl and 3,6-dihydro-2H-thiopyran-6-yl. The term piperazinyl also known as piperazidinyl as used herein includes piperazin-1-yl and piperazin-2-yl. The term molpholinyl as used herein includes morpholin-2-yl, morpholin-3-yl and morpholin-4-yl. The term thiomorpholinyl as used herein includes thiomorpholin-2-yl, thiomorpholin-3-yl and thiomorpholin-4-yl. The term dioxanyl as used herein includes 1,2-dioxan-3-yl, 1,2-dioxan-4-yl, 1,3-dioxan-2-yl, 1,3-dioxan-4-yl, 1,3-dioxan-5-yl and 1,4-dioxan-2-yl. The term dithianyl as used herein includes 1,2-dithian-3-yl, 1,2-dithian-4-yl, 1,3-dithian-2-yl, 1,3-dithian-4-yl, 1,3-dithian-5-yl and 1,4-dithian-2-yl. The term oxathianyl as used herein includes oxathian-2-yl and oxathian-3-yl. The term trioxanyl as used herein includes 1,2,3-trioxan-4-yl, 1,2,3-trioxay-5-yl, 1,2,4-trioxay-3-yl, 1,2,4-trioxay-5-yl, 1,2,4-trioxay-6-yl and 1,3,4-trioxay-2-yl. The term azepanyl as used herein includes azepan-1-yl, azepan-2-yl, azepan-1-yl, azepan-3-yl and azepan-4-yl. The term homopiperazinyl as used herein includes homopiperazin-1-yl, homopiperazin-2-yl, homopiperazin-3-yl and homopiperazin-4-yl. The term indolinyl as used herein includes indolin-1-yl, indolin-2-yl, indolin-3-yl, indolin-4-yl, indolin-5-yl, indolin-6-yl, and indolin-7-yl. The term quinolizinyl as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl. The term isoindolinyl as used herein includes isoindolin-1-yl, isoindolin-2-yl, isoindolin-3-yl, isoindolin-4-yl, isoindolin-5-yl, isoindolin-6-yl, and isoindolin-7-yl. The term 3H-indolyl as used herein includes 3H-indol-2-yl, 3H-indol-3-yl, 3H-indol-4-yl, 3H-indol-5-yl, 3H-indol-6-yl, and 3H-indol-7-yl. The term quinolizinyl as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl. The term quinolizinyl as used herein includes quinolizidin-1-yl, quinolizidin-2-yl, quinolizidin-3-yl and quinolizidin-4-yl. The term tetrahydroquinolinyl as used herein includes tetrahydroquinolin-1-yl, tetrahydroquinolin-2-yl, tetrahydroquinolin-3-yl, tetrahydroquinolin-4-yl, tetrahydroquinolin-5-yl, tetrahydroquinolin-6-yl, tetrahydroquinolin-7-yl and tetrahydroquinolin-8-yl. The term tetrahydroisoquinolinyl as used herein includes tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, tetrahydroisoquinolin-5-yl, tetrahydroisoquinolin-6-yl, tetrahydroisoquinolin-7-yl and tetrahydroisoquinolin-8-yl. The term 1H-pyrrolizine as used herein includes 1H-pyrrolizin-1-yl, 1H-pyrrolizin-2-yl, 1H-pyrrolizin-3-yl, 1H-pyrrolizin-5-yl, 1H-pyrrolizin-6-yl and 1H-pyrrolizin-7-yl.

[0166] The term 3H-pyrrolizine as used herein includes 3H-pyrrolizin-1-yl, 3H-pyrrolizin-2-yl, 3H-pyrrolizin-3-yl, 3H-pyrrolizin-5-yl, 3H-pyrrolizin-6-yl and 3H-pyrrolizin-7-yl.

[0167] When the suffix ene is used in conjunction with a heterocyclyl group, i.e. heterocyclylene, this is intended to mean the heterocyclyl group as defined herein having two single bonds as points of attachment to other groups.

[0168] The term heterocyclyloxy, as a group or part of a group, refers to a group having the formula OR.sup.i wherein R.sup.i is heterocyclyl as defined herein above.

[0169] The term heterocyclylC.sub.1-6alkyloxy, as a group or part of a group, refers to a group having the formula OR.sup.aR.sup.i wherein R.sup.i is heterocyclyl, and R.sup.a is C.sub.1-6alkylene as defined herein above.

[0170] The term heterocyclylC.sub.1-6alkyl, as a group or part of a group, means a C.sub.1-6alkyl as defined herein, wherein at least one hydrogen atom is replaced by at least one heterocyclyl as defined herein.

[0171] The term heterocyclyleneC.sub.1-6alkylene, as a group or part of a group, refers to a group having the formula R.sup.jR.sup.a wherein R.sup.j is heterocyclylene as defined herein and R.sup.a is C.sub.1-6alkylene as defined herein.

[0172] The term heteroaryl as a group or part of a group, refers but is not limited to 5 to 12 carbon-atom aromatic rings or ring systems containing 1 or 2 rings which can be fused together or linked covalently, typically containing 5 to 6 atoms; at least one of which is aromatic in which one or more carbon atoms in one or more of these rings can be replaced by N, O and/or S atoms where the N and S heteroatoms may optionally be oxidized and the N heteroatoms may optionally be quaternized, and wherein at least one carbon atom of said heteroaryl can be oxidized to form at least one CO. Such rings may be fused to an aryl, cycloalkyl, heteroaryl or heterocyclyl ring. Non-limiting examples of such heteroaryl, include: pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazinyl, dioxinyl, thiazinyl, triazinyl, imidazo[2,1-b][1,3]thiazolyl, thieno[3,2-b]furanyl, thieno[3,2-b]thiophenyl, thieno[2,3-d][1,3]thiazolyl, thieno[2,3-d]imidazolyl, tetrazolo[1,5-a]pyridinyl, indolyl, indolizinyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, isobenzothiophenyl, indazolyl, benzimidazolyl, 1,3-benzoxazolyl, 1,2-benzisoxazolyl, 2,1-benzisoxazolyl, 1,3-benzothiazolyl, 1,2-benzoisothiazolyl, 2,1-benzoisothiazolyl, benzotriazolyl, 1,2,3-benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl, benzo[d]oxazol-2 (3H)-one, 2,3-dihydro-benzofuranyl, thienopyridinyl, purinyl, imidazo[1,2-a]pyridinyl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridin-1(2H)-yl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridin-1(2H)-yl, 1,3-benzodioxolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl; preferably said heteroaryl group is selected from the group consisting of pyridyl, 1,3-benzodioxolyl, benzo[d]oxazol-2(3H)-one, 2,3-dihydro-benzofuranyl, pyrazinyl, pyrazolyl, pyrrolyl, isoxazolyl, thiophenyl, imidazolyl, benzimidazolyl, pyrimidinyl, triazolyl and thiazolyl.

[0173] The term pyrrolyl (also called azolyl) as used herein includes pyrrol-1-yl, pyrrol-2-yl and pyrrol-3-yl.

[0174] The term furanyl (also called furyl) as used herein includes furan-2-yl and furan-3-yl (also called furan-2-yl and furan-3-yl). The term thiophenyl (also called thienyl) as used herein includes thiophen-2-yl and thiophen-3-yl (also called thien-2-yl and thien-3-yl). The term pyrazolyl (also called 1H-pyrazolyl and 1,2-diazolyl) as used herein includes pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl and pyrazol-5-yl. The term imidazolyl as used herein includes imidazol-1-yl, imidazol-2-yl, imidazol-4-yl and imidazol-5-yl. The term oxazolyl (also called 1,3-oxazolyl) as used herein includes oxazol-2-yl, oxazol-4-yl and oxazol-5-yl. The term isoxazolyl (also called 1,2-oxazolyl), as used herein includes isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl. The term thiazolyl (also called 1,3-thiazolyl), as used herein includes thiazol-2-yl, thiazol-4-yl and thiazol-5-yl (also called 2-thiazolyl, 4-thiazolyl and 5-thiazolyl). The term isothiazolyl (also called 1,2-thiazolyl) as used herein includes isothiazol-3-yl, isothiazol-4-yl, and isothiazol-5-yl. The term triazolyl as used herein includes 1H-triazolyl and 4H-1,2,4-triazolyl, 1H-triazolyl includes 1H-1,2,3-triazol-1-yl, 1H-1,2,3-triazol-4-yl, 1H-1,2,3-triazol-5-yl, 1H-1,2,4-triazol-1-yl, 1H-1,2,4-triazol-3-yl and 1H-1,2,4-triazol-5-yl. 4H-1,2,4-triazolyl includes 4H-1,2,4-triazol-4-yl, and 4H-1,2,4-triazol-3-yl. The term oxadiazolyl as used herein includes 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,2,5-oxadiazol-3-yl and 1,3,4-oxadiazol-2-yl. The term thiadiazolyl as used herein includes 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,2,5-thiadiazol-3-yl (also called furazan-3-yl) and 1,3,4-thiadiazol-2-yl. The term tetrazolyl as used herein includes 1H-tetrazol-1-yl, 1H-tetrazol-5-yl, 2H-tetrazol-2-yl, and 2H-tetrazol-5-yl. The term oxatriazolyl as used herein includes 1,2,3,4-oxatriazol-5-yl and 1,2,3,5-oxatriazol-4-yl. The term thiatriazolyl as used herein includes 1,2,3,4-thiatriazol-5-yl and 1,2,3,5-thiatriazol-4-yl. The term pyridinyl (also called pyridyl) as used herein includes pyridin-2-yl, pyridin-3-yl and pyridin-4-yl (also called 2-pyridyl, 3-pyridyl and 4-pyridyl). The term pyrimidyl as used herein includes pyrimid-2-yl, pyrimid-4-yl, pyrimid-5-yl and pyrimid-6-yl. The term pyrazinyl as used herein includes pyrazin-2-yl and pyrazin-3-yl. The term pyridazinyl as used herein includes pyridazin-3-yl and pyridazin-4-yl. The term oxazinyl (also called 1,4-oxazinyl) as used herein includes 1,4-oxazin-4-yl and 1,4-oxazin-5-yl. The term dioxinyl (also called 1,4-dioxinyl) as used herein includes 1,4-dioxin-2-yl and 1,4-dioxin-3-yl. The term thiazinyl (also called 1,4-thiazinyl) as used herein includes 1,4-thiazin-2-yl, 1,4-thiazin-3-yl, 1,4-thiazin-4-yl, 1,4-thiazin-5-yl and 1,4-thiazin-6-yl. The term triazinyl as used herein includes 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl and 1,2,3-triazin-5-yl. The term imidazo[2,1-b][1,3]thiazolyl as used herein includes imidazo[2,1-b][1,3]thiazoi-2-yl, imidazo[2,1-b][1,3]thiazol-3-yl, imidazo[2,1-b][1,3]thiazol-5-yl and imidazo[2,1-b][1,3]thiazol-6-yl. The term thieno[3,2-b]furanyl as used herein includes thieno[3,2-b]furan-2-yl, thieno[3,2-b]furan-3-yl, thieno[3,2-b]furan-4-yl, and thieno[3,2-b]furan-5-yl. The term thieno[3,2-b]thiophenyl as used herein includes thieno[3,2-b]thien-2-yl, thieno[3,2-b]thien-3-yl, thieno[3,2-b]thien-5-yl and thieno[3,2-b]thien-6-yl. The term thieno[2,3-d][1,3]thiazolyl as used herein includes thieno[2,3-d][1,3]thiazol-2-yl, thieno[2,3-d][1,3]thiazol-5-yl and thieno[2,3-d][1,3]thiazol-6-yl. The term thieno[2,3-d]imidazolyl as used herein includes thieno[2,3-d]imidazol-2-yl, thieno[2,3-d]imidazol-4-yl and thieno[2,3-d]imidazol-5-yl. The term tetrazolo[1,5-a]pyridinyl as used herein includes tetrazolo[1,5-a]pyridine-5-yl, tetrazolo[1,5-a]pyridine-6-yl, tetrazolo[1,5-a]pyridine-7-yl, and tetrazolo[1,5-a]pyridine-8-yl. The term indolyl as used herein includes indol-1-yl, indol-2-yl, indol-3-yl,-indol-4-yl, indol-5-yl, indol-6-yl and indol-7-yl. The term indolizinyl as used herein includes indolizin-1-yl, indolizin-2-yl, indolizin-3-yl, indolizin-5-yl, indolizin-6-yl, indolizin-7-yl, and indolizin-8-yl. The term isoindolyl as used herein includes isoindol-1-yl, isoindol-2-yl, isoindol-3-yl, isoindol-4-yl, isoindol-5-yl, isoindol-6-yl and isoindol-7-yl. The term benzofuranyl (also called benzo[b]furanyl) as used herein includes benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl and benzofuran-7-yl. The term isobenzofuranyl (also called benzo[c]furanyl) as used herein includes isobenzofuran-1-yl, isobenzofuran-3-yl, isobenzofuran-4-yl, isobenzofuran-5-yl, isobenzofuran-6-yl and isobenzofuran-7-yl. The term benzothiophenyl (also called benzo[b]thienyl) as used herein includes 2-benzo[b]thiophenyl, 3-benzo[b]thiophenyl, 4-benzo[b]thiophenyl, 5-benzo[b]thiophenyl, 6-benzo[b]thiophenyl and -7-benzo[b]thiophenyl (also called benzothien-2-yl, benzothien-3-yl, benzothien-4-yl, benzothien-5-yl, benzothien-6-yl and benzothien-7-yl). The term isobenzothiophenyl (also called benzo[c]thienyl) as used herein includes isobenzothien-1-yl, isobenzothien-3-yl, isobenzothien-4-yl, isobenzothien-5-yl, isobenzothien-6-yl and isobenzothien-7-yl. The term indazolyl (also called 1H-indazolyl or 2-azaindolyl) as used herein includes 1H-indazol-1-yl, 1H-indazol-3-yl, 1H-indazol-4-yl, 1H-indazol-5-yl, 1H-indazol-6-yl, 1H-indazol-7-yl, 2H-indazol-2-yl, 2H-indazol-3-yl, 2H-indazol-4-yl, 2H-indazol-5-yl, 2H-indazol-6-yl, and 2H-indazol-7-yl. The term benzimidazolyl as used herein includes benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-4-yl, benzimidazol-5-yl, benzimidazol-6-yl and benzimidazol-7-yl. The term 1,3-benzoxazolyl as used herein includes 1,3-benzoxazol-2-yl, 1,3-benzoxazol-4-yl, 1,3-benzoxazol-5-yl, 1,3-benzoxazol-6-yl and 1,3-benzoxazol-7-yl. The term 1,2-benzisoxazolyl as used herein includes 1,2-benzisoxazol-3-yl, 1,2-benzisoxazol-4-yl, 1,2-benzisoxazol-5-yl, 1,2-benzisoxazol-6-yl and 1,2-benzisoxazol-7-yl. The term 2,1-benzisoxazolyl as used herein includes 2,1-benzisoxazol-3-yl, 2,1-benzisoxazol-4-yl, 2,1-benzisoxazol-5-yl, 2,1-benzisoxazol-6-yl and 2,1-benzisoxazol-7-yl. The term 1,3-benzothiazolyl as used herein includes 1,3-benzothiazol-2-yl, 1,3-benzothiazol-4-yl, 1,3-benzothiazol-5-yl, 1,3-benzothiazol-6-yl and 1,3-benzothiazol-7-yl. The term 1,2-benzoisothiazolyl as used herein includes 1,2-benzisothiazol-3-yl, 1,2-benzisothiazol-4-yl, 1,2-benzisothiazol-5-yl, 1,2-benzisothiazol-6-yl and 1,2-benzisothiazol-7-yl. The term 2,1-benzoisothiazolyl as used herein includes 2,1-benzisothiazol-3-yl, 2,1-benzisothiazol-4-yl, 2,1-benzisothiazol-5-yl, 2,1-benzisothiazol-6-yl and 2,1-benzisothiazol-7-yl. The term benzotriazolyl as used herein includes benzotriazol-1-yl, benzotriazol-4-yl, benzotriazol-5-yl, benzotriazol-6-yl and benzotriazol-7-yl. The term 1,2,3-benzoxadiazolyl as used herein includes 1,2,3-benzoxadiazol-4-yl, 1,2,3-benzoxadiazol-5-yl, 1,2,3-benzoxadiazol-6-yl and 1,2,3-benzoxadiazol-7-yl. The term 2,1,3-benzoxadiazolyl as used herein includes 2,1,3-benzoxadiazol-4-yl, 2,1,3-benzoxadiazol-5-yl, 2,1,3-benzoxadiazol-6-yl and 2,1,3-benzoxadiazol-7-yl. The term 1,2,3-benzothiadiazolyl as used herein includes 1,2,3-benzothiadiazol-4-yl, 1,2,3-benzothiadiazol-5-yl, 1,2,3-benzothiadiazol-6-yl and 1,2,3-benzothiadiazol-7-yl. The term 2,1,3-benzothiadiazolyl as used herein includes 2,1,3-benzothiadiazol-4-yl, 2,1,3-benzothiadiazol-5-yl, 2,1,3-benzothiadiazol-6-yl and 2,1,3-benzothiadiazol-7-yl. The term thienopyridinyl as used herein includes thieno[2,3-b]pyridinyl, thieno[2,3-c]pyridinyl, thieno[3,2-c]pyridinyl and thieno[3,2-b]pyridinyl. The term purinyl as used herein includes purin-2-yl, purin-6-yl, purin-7-yl and purin-8-yl. The term imidazo[1,2-a]pyridinyl, as used herein includes imidazo[1,2-a]pyridin-2-yl, imidazo[1,2-a]pyridin-3-yl, imidazo[1,2-a]pyridin-4-yl, imidazo[1,2-a]pyridin-5-yl, imidazo[1,2-a]pyridin-6-yl and imidazo[1,2-a]pyridin-7-yl. The term 1,3-benzodioxolyl, as used herein includes 1,3-benzodioxol-4-yl, 1,3-benzodioxol-5-yl, 1,3-benzodioxol-6-yl, and 1,3-benzodioxol-7-yl. The term quinolinyl as used herein includes quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-5-yl, quinolin-6-yl, quinolin-7-yl and quinolin-8-yl. The term isoquinolinyl as used herein includes isoquinolin-1-yl, isoquinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, isoquinolin-6-yl, isoquinolin-7-yl and isoquinolin-8-yl. The term cinnolinyl as used herein includes cinnolin-3-yl, cinnolin-4-yl, cinnolin-5-yl, cinnolin-6-yl, cinnolin-7-yl and cinnolin-8-yl. The term quinazolinyl as used herein includes quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl and quinazolin-8-yl. The term quinoxalinyl as used herein includes quinoxalin-2-yl, quinoxalin-5-yl, and quinoxalin-6-yl.

[0175] When the suffix ene is used in conjunction with a heteroaryl group, i.e. heteroarylene, this is intended to mean the heteroaryl group as defined herein having two single bonds as points of attachment to other groups.

[0176] The term heteroaryloxy, as a group or part of a group, refers to a group having the formula OR.sup.k wherein R.sup.k is heteroaryl as defined herein above.

[0177] The term heteroarylC.sub.1-6alkyl, as a group or part of a group, means a C.sub.1-6alkyl as defined herein, wherein at least one hydrogen atom is replaced by at least one heteroaryl as defined herein.

[0178] The term heteroarylC.sub.1-6alkyloxy, as a group or part of a group, refers to a group having the formula OR.sup.aR.sup.k wherein R.sup.k is heteroaryl, and R.sup.a is C.sub.1-6alkylene as defined herein above.

[0179] The term heteroaryleneC.sub.1-6alkylene, as a group or part of a group, refers to a group having the formula R.sup.mR.sup.a wherein R.sup.m is heteroarylene as defined herein and R.sup.a is C.sub.1-6alkylene as defined herein.

[0180] The term cyanoC.sub.1-6alkyl as a group or part of a group, refers to a C.sub.1-6alkyl group having the meaning as defined above wherein at least one hydrogen atom is replaced with at least one cyano group as defined herein. Non-limiting examples of such cyanoC.sub.1-6alkyl groups include cyanomethyl, 1-cyanoethyl, 1-cyanopropyl and the like.

[0181] The term cyanoC.sub.1-6alkyloxy, as a group or part of a group, refers to a group having the formula OR.sup.n wherein R.sup.n is cyanoC.sub.1-6alkyl as defined herein above.

[0182] The term C.sub.1-6alkylthio, as a group or part of a group, refers to a group having the formula SR.sup.b wherein R.sup.b is C.sub.1-6alkyl as defined herein above. Non-limiting examples of C.sub.1-6alkylthio groups include methylthio (SCH.sub.3), ethylthio (SCH.sub.2CH.sub.3), n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, tert-butylthio and the like.

[0183] The term C.sub.2-6alkenylthio, as a group or part of a group, refers to a group having the formula SR.sup.d wherein R.sup.d is C.sub.2-6alkenyl as defined herein above.

[0184] The term C.sub.2-6alkynylthio, as a group or part of a group, refers to a group having the formula SR.sup.e wherein R.sup.e is C.sub.2-6alkynyl as defined herein above.

[0185] The term C.sub.6-12arylthio, as a group or part of a group, refers to a group having the formula SR.sup.g wherein R.sup.g is C.sub.6-12aryl as defined herein above.

[0186] The term C.sub.3-12cycloalkylthio, as a group or part of a group, refers to a group having the formula SR.sup.f wherein R.sup.f is C.sub.3-12cycloalkyl as defined herein above.

[0187] The term C.sub.6-12arylC.sub.1-6alkylthio, as a group or part of a group, refers to a group having the formula SR.sup.aR.sup.g wherein R.sup.a is C.sub.1-6alkylene and R.sup.g is C.sub.6-12aryl as defined herein above.

[0188] The term heterocyclylthio, as a group or part of a group, refers to a group having the formula SR.sup.i wherein R.sup.i is heterocyclyl as defined herein above.

[0189] The term heteroarylthio, as a group or part of a group, refers to a group having the formula SR.sup.k wherein R.sup.k is heteroaryl as defined herein above.

[0190] The term heterocyclylC.sub.1-6alkylthio, as a group or part of a group, refers to a group having the formula SR.sup.aR.sup.i wherein R.sup.a is C.sub.1-6alkylene and R.sup.i is heterocyclyl as defined herein above.

[0191] The term heteroarylC.sub.1-6alkylthio, as a group or part of a group, refers to a group having the formula SR.sup.aR.sup.k wherein R.sup.a is C.sub.1-6alkylene and R.sup.k is heteroaryl as defined herein above.

[0192] The term cyanoC.sub.1-6alkylthio, as a group or part of a group, refers to a group having the formula SR.sup.n wherein R.sup.n is cyanoC.sub.1-6alkyl as defined herein above.

[0193] The term mono- or di-C.sub.1-6alkylamino, as a group or part of a group, refers to a group of formula N(R.sup.o)(R.sup.p) wherein R.sup.o and R.sup.p are each independently selected from hydrogen, or C.sub.1-6alkyl, wherein at least one of R.sup.o or R.sup.p is C.sub.1-6alkyl. Thus, alkylamino include mono-alkyl amino group (e.g. mono-C.sub.1-6alkylamino group such as methylamino and ethylamino), and di-alkylamino group (e.g. di-C.sub.1-6alkylamino group such as dimethylamino and diethylamino). Non-limiting examples of suitable mono- or di-C.sub.1-6alkylamino groups include n-propylamino, isopropylamino, n-butylamino, i-butylamino, sec-butylamino, t-butylamino, pentylamino, n-hexylamino, di-n-propylamino, d i-propyl amino, ethylmethylamino, methyl-n-propylamino, methyl-i-propylamino, n-butylmethylamino, butylmethylamino, t-butylmethylamino, ethyl-n-propylamino, ethyl-i-propylamino, n-butylethylamino, i-butyl ethyl amino, t-butyl ethyl amino, di-n-butylamino, di-i-butylamino, methylpentyl amino, methylhexylamino, ethylpentylamino, ethylhexylamino, propylpentylamino, propylhexylamino, and the like.

[0194] The term mono- or di-C.sub.6-12arylamino, as a group or part of a group, refers to a group of formula N(R.sup.q)(R.sup.r) wherein R.sup.q and R.sup.r are each independently selected from hydrogen, C.sub.6-12aryl, or C.sub.1-6alkyl, wherein at least one of R.sup.q or R.sup.r is C.sub.6-12aryl.

[0195] The term mono- or di-C.sub.3-8cycloalkylamino, as a group or part of a group, refers to a group of formula N(R.sup.s)(R.sup.t) wherein R.sup.s and R.sup.t are each independently selected from hydrogen, C.sub.3-8cycloalkyl, or C.sub.1-6alkyl, wherein at least one of R.sup.s or R.sup.t is C.sub.3-8cycloalkyl.

[0196] The term aminoC.sub.1-6alkyl, as a group or part of a group, refers to a group of formula R.sup.aNR.sup.oR.sup.p wherein R.sup.a is C.sub.1-6alkylene, R.sup.o is hydrogen or C.sub.1-6alkyl as defined herein, and R.sup.p is hydrogen or C.sub.1-6alkyl as defined herein.

[0197] The term mono- or di-heteroarylamino, as a group or part of a group, refers to a group of formula) N(R.sup.u)(R.sup.v) wherein R.sup.u and R.sup.v are each independently selected from hydrogen, heteroaryl, or C.sub.1-6alkyl, wherein at least one of R.sup.u or R.sup.v is heteroaryl as defined herein.

[0198] The term mono- or di-heterocyclylamino, as a group or part of a group, refers to a group of formula N(R.sup.w)(R.sup.x) wherein R.sup.w and R.sup.x are each independently selected from hydrogen, heterocyclyl, or C.sub.1-6alkyl, wherein at least one of R.sup.w or R.sup.x is heterocyclyl as defined herein.

[0199] The term hydroxycarbonylC.sub.1-6alkyl, as a group or part of a group, refers to a group of formula R.sup.aCOOH, wherein R.sup.a is C.sub.1-6alkylene as defined herein.

[0200] The term C.sub.1-6alkyloxycarbonyl, as a group or part of a group, refers to a group of formula COOR.sup.b, wherein R.sup.b is C.sub.1-6alkyl as defined herein.

[0201] The term mono- or diC.sub.1-6alkylaminocarbonyl, as a group or part of a group, refers to a group of formula CONR.sup.oR.sup.p wherein R.sup.oR.sup.p are each independently selected from hydrogen, or C.sub.1-6alkyl, wherein at least one of R.sup.o or R.sup.p is C.sub.1-6alkyl.

[0202] The term C.sub.1-6alkylcarbonyl, as a group or part of a group, refers to a group of formula COR.sup.b, wherein R.sup.b is C.sub.1-6alkyl as defined herein.

[0203] The term C.sub.1-6alkylcarbonylamino, as a group or part of a group, refers to a group of formula NR.sup.oCOR.sup.b, wherein R.sup.o is selected from hydrogen, or C.sub.1-6alkyl and R.sup.b is C.sub.1-6alkyl as defined herein.

[0204] The term mono or di-C.sub.1-6alkylaminocarbonylC.sub.1-6alkyl, as a group or part of a group, refers to a group of formula R.sup.aCONR.sup.oR.sup.p wherein R.sup.oR.sup.p are each independently selected from hydrogen, or C.sub.1-6alkyl, wherein at least one of R.sup.o or R.sup.p is C.sub.1-6alkyl, and R.sup.a is C.sub.1-6alkylene as defined herein.

[0205] The term leaving group as used herein means a chemical group which is susceptible to be displaced by a nucleophile or cleaved off or hydrolyzed in basic or acidic conditions. In a particular embodiment, a leaving group is selected from a halogen atom (e.g., Cl, Br, I) or a trihalomethyl group (e.g. CCl.sub.3, Cl.sub.3, CBr.sub.3).

[0206] The term a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring as used herein encompasses saturated or unsaturated carbon only membered rings, as well as saturated or unsaturated heteroatoms containing rings. The term a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring as used herein refers to saturated carbon only membered ring such as C.sub.3-7cycloalkyl and C.sub.3-7cycloalkylene.

[0207] Whenever used in the present invention the term compounds of the invention or a similar term is meant to include the compounds of general formula (I) or (II) and any subgroup thereof. This term also refers to the compounds as depicted in Table 1 and their derivatives, N-oxides, salts, solvates, hydrates, stereoisomeric forms, racemic mixtures, tautomeric forms, optical isomers, analogues, pro-drugs, esters and metabolites, as well as their quaternized nitrogen analogues. The N-oxide forms of said compounds are meant to comprise compounds wherein one or several nitrogen atoms are oxidized to the so-called N-oxide.

[0208] Preferred statements (features) and embodiments of the compounds and processes of this invention are now set forth. Each statements and embodiments of the invention so defined may be combined with any other statement and/or embodiments unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.

Numbered statements of this invention are: [0209] 1. A compound of formula (I) or (II); or a stereoisomer, enantiomer, racemic, or tautomer thereof,

##STR00005## [0210] wherein, [0211] n is an integer selected from 0, 1, 2 or 3; [0212] R.sup.1 is selected from the group consisting of C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0213] R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.1; [0214] R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.2; [0215] L.sup.1 is a single bond, or is a group of formula (i);

##STR00006## [0216] wherein the left side of the group of formula (i) is attached to R.sup.2 and the right side thereof is attached to the oxadiazole ring; and wherein, [0217] m is an integer selected from 0, 1, 2, 3 or 4; [0218] p is an integer selected from 0, 1, 2, 3 or 4; [0219] L.sup.4 is a single bond, or is selected from the group consisting of O, and NR.sup.8; [0220] R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0221] R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0222] or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; [0223] R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0224] R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0225] or R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; [0226] R.sup.8 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0227] L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, PO.sub.3, and (CR.sup.9R.sup.10).sub.q; [0228] wherein, [0229] q is an integer selected from 1, 2 or 3; [0230] R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0231] R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0232] or R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; [0233] L.sup.3 is a single bond or is selected from the group consisting of (CR.sup.11R.sup.12).sub.r, O, and NR.sup.13; wherein, [0234] r is an integer selected from 1, 2 or 3; [0235] R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0236] R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0237] or R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; [0238] R.sup.13 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0239] wherein at least one of L.sup.2, L.sup.3 is not a single bond; [0240] L.sup.5 is a single bond or CO; [0241] each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyano C.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12 arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; [0242] and wherein at least one carbon atom or heteroatom of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0243] each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyano C.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12 arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; [0244] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0245] each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; [0246] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0247] each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; [0248] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0249] or wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-, 6-, or 7-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0250] each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.2-6 alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; [0251] wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2, [0252] each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; [0253] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0254] each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-2 arylene, C.sub.3-8cycloalkylene, C.sub.6-12 aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene*, and heteroaryleneC.sub.1-6alkylene*; wherein * represents where R.sup.21 is bound to CO; [0255] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkylene, C.sub.2-6 alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene, or heteroaryleneC.sub.1-6alkylene can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0256] each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, S(O)R.sup.19, S(O).sub.2R.sup.19, SO.sub.2NR.sup.17R.sup.18, nitro, NR.sup.20C(O)R.sup.19, R.sup.21C(O)NR.sup.17R.sup.18, NR.sup.20S(O).sub.2R.sup.19, and NR.sup.20C(O)NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2, [0257] each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, S(O)R.sup.19, S(O).sub.2R.sup.19, SO.sub.2NR.sup.17R.sup.18, nitro, NR.sup.20C(O)R.sup.19, R.sup.21C(O)NR.sup.17R.sup.18, NR.sup.20S(O).sub.2R.sup.19, and NR.sup.20C(O)NR.sup.17R.sup.18; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0258] and with the proviso that for a compound of formula (I) when R.sup.2 is C.sub.6-12aryl; L.sup.3 is a single bond, (CR.sup.11R.sup.12).sub.r, O, or NR.sup.13; then R.sup.3 is not hydrogen, C.sub.1-6alkyl, hydroxyl, or OR.sup.15; [0259] and with the proviso that for a compound of formula (I) when L.sup.1 is a single bond, R.sup.2 is not hydrogen; [0260] and with the proviso that said compound is not [0261] 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0262] 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0263] 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0264] 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0265] 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; [0266] 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0267] 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; [0268] 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0269] 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; [0270] 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; [0271] 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; [0272] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0273] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; [0274] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; [0275] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; [0276] 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0277] 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; [0278] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; [0279] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; [0280] 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0281] 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0282] 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0283] 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0284] 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; [0285] 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0286] 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; [0287] 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; [0288] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; [0289] 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0290] 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; [0291] 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0292] 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; [0293] N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; [0294] 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; [0295] 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; [0296] 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole; [0297] or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof [0298] 2. The compound according to statement 1, having structural formula (IA) or (IIA),

##STR00007## [0299] wherein L.sup.1, L.sup.3, L.sup.5, n, R.sup.1, R.sup.2 and R.sup.3 have the same meaning as that defined in statement 1. [0300] 3. The compound according to statements 1 or 2, having structural formula (IB) or (IIB),

##STR00008## [0301] wherein, L.sup.1, n, R.sup.1, R.sup.2 and R.sup.3 have the same meaning as that defined in statements 1 or 2. [0302] 4. The compound according to any one of statements 1 to 3, wherein R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyano C.sub.1-6alkyloxy, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, or mono or di-heteroarylamino, can be unsubstituted or substituted with -one, two, or three Z.sup.1. [0303] 5. The compound according to any one of statements 1 to 4, wherein R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroaryl C.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, halo C.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, C.sub.1-6alkylthio, halo C.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, can be unsubstituted or substituted with one, two, or three Z.sup.1. [0304] 6. The compound according to any one of statements 1 to 5, wherein R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, halo C.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.1-6alkyloxy, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, can be unsubstituted or substituted with one, two, or three Z.sup.1. [0305] 7. The compound according to any one of statements 1 to 6, wherein R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6 alkylthio, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.1-6alkyloxy, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, or haloC.sub.1-6alkyloxy can be unsubstituted or substituted with one, two, or three Z.sup.1. [0306] 8. The compound according to any one of statements 1 to 7, wherein R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyl, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.1-6alkyloxy, or haloC.sub.1-6alkyl, can be unsubstituted or substituted one, two, or three Z.sup.1. [0307] 9. The compound according to any one of statements 1 to 8, having structural formula (IC) or (IIC),

##STR00009## [0308] wherein, L.sup.3, n, R.sup.1, R.sup.2 and R.sup.3 have the same meaning as defined in any one of statements 1 to 8. [0309] 10. The compound according to any one of statements 1 to 8, having structural formula (ID) or (IID),

##STR00010## [0310] wherein, L.sup.3, n, R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5, have the same meaning as defined in any one of statements 1 to 8. [0311] 11. The compound according to any one of statements 1 to 8, having structural formula (IE) or (IIE),

##STR00011## [0312] wherein, L.sup.1, L.sup.2, L.sup.3, L.sup.5, n, R.sup.1, R.sup.2, R.sup.3, and Z.sup.1 have the same meaning as that defined in any one of statements 1 to 8, and wherein, w is an integer selected from 1, 2, or 3. [0313] 12. The compound according to any one of statements 1 to 8 and 11, having structural formula (IF) or (IIF)

##STR00012## [0314] wherein, L.sup.1, L.sup.3, L.sup.5, n, R.sup.1, R.sup.3, and Z.sup.1 have the same meaning as that defined in any one of statements 1 to 8 and 11, and wherein, w is an integer selected from 1, 2, or 3. [0315] 13. The compound according to any one of statements 1 to 11, having structural formula (IG) or (IIG),

##STR00013## [0316] wherein, L.sup.2, L.sup.3, L.sup.5, n, R.sup.1, R.sup.3, R.sup.4, R.sup.5, and Z.sup.1 have the same meaning as defined in any one of statements 1 to 11, and wherein, w is an integer selected from 1, 2, or 3. [0317] 14. The compound according to any one of statements 1 to 13, wherein [0318] w is an integer selected from 1, 2, or 3; [0319] R.sup.4 is selected from the group consisting of C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0320] R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, halo C.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; [0321] or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring. [0322] 15. The compound according to any one of statements 1 to 14, having structural formula (IH) or (IIH),

##STR00014## [0323] wherein, L.sup.3, L.sup.5, n, R.sup.1, R.sup.3, R.sup.4, R.sup.5, and Z.sup.1 and w have the same meaning as defined in any one of statements 1 to 15, and wherein, w is an integer selected from 1, 2, or 3. [0324] 16. The compound according to any one of statements 1 to 15, wherein R.sup.4 is selected from the group consisting of C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; and R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and halo C.sub.1-6alkyloxy. [0325] 17. The compound according to any one of statements 1 to 16, wherein R.sup.4 is selected from the group consisting of C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, halo C.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; and R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0326] 18. The compound according to any one of statements 1 to 17, wherein R.sup.4 is selected from the group consisting of C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; and R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0327] 19. The compound according to any one of statements 1 to 18, wherein R.sup.4 is selected from the group consisting of C.sub.1-6alkyl, and halo. [0328] 20. The compound according to any one of statements 11 to 18, wherein w is an integer selected from 1, or 2. [0329] 21. The compound according to any one of statements 1 to 20, wherein R.sup.1 is selected from the group consisting of C.sub.1-6alkyl, and halo. [0330] 22. The compound according to any one of statements 1 to 21, wherein R.sup.1 is C.sub.1-6alkyl. [0331] 23. The compound according to any one of statements 1 to 22, wherein n is an integer selected from 0 or 1. [0332] 24. The compound according to any one of statements 1 to 23, wherein n is 0. [0333] 25. The compound according to any one of statements 1 to 24, wherein R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, halo C.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, can be unsubstituted or substituted with one, two, or three Z.sup.2. [0334] 26. The compound according to any one of statements 1 to 25, wherein R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6 alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6 alkylthio, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, and mono or di-C.sub.3-8cycloalkylamino; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, cyanoC.sub.1-6alkyloxy, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, halo C.sub.1-6alkyloxy, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, can be unsubstituted or substituted with one, two, or three Z.sup.2. [0335] 27. The compound according to any one of statements 1 to 26, wherein R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, and mono or di-C.sub.6-12arylamino; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, can be unsubstituted or substituted with one, two, or three Z.sup.2. [0336] 28. The compound according to any one of statements 1 to 27, wherein R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, heterocyclyl, heteroaryl, halo, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, and mono or di C.sub.1-6alkylamino; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, heterocyclyl, heteroaryl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di-C.sub.1-6alkylamino, can be unsubstituted or substituted with one, two, or three Z.sup.2. [0337] 29. The compound according to any one of statements 1 to 28, wherein m is an integer selected from 0, 1, or 2. [0338] 30. The compound according to any one of statements 1 to 29, wherein m is an integer selected from 0, or 1. [0339] 31. The compound according to any one of statements 1 to 30, wherein in is 1. [0340] 32. The compound according to any one of statements 1 to 31, wherein p is an integer selected from 0, 1, or 2. [0341] 33. The compound according to any one of statements 1 to 32, wherein p is an integer selected from 0, or 1. [0342] 34. The compound according to any one of statements 1 to 33, wherein p is 0. [0343] 35. The compound according to any one of statements 1 to 34, wherein L.sup.4 is a single bond, or is selected from the group consisting of O, NH, and N(C.sub.1-6alkyl)-. [0344] 36. The compound according to any one of statements 1 to 35, wherein L.sup.4 is a single bond, or is selected from the group consisting of O, and NH. [0345] 37. The compound according to any one of statements 1 to 36, wherein L.sup.4 is a single bond. [0346] 38. The compound according to any one of statements 1 to 37, wherein R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0347] 39. The compound according to any one of statements 1 to 38, wherein R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0348] 40. The compound according to any one of statements 1 to 39, wherein R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0349] 41. The compound according to any one of statements 1 to 40, wherein R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0350] 42. The compound according to any one of statements 1 to 41, wherein R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0351] 43. The compound according to any one of statements 1 to 42, wherein R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0352] 44. The compound according to any one of statements 1 to 43, wherein R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0353] 45. The compound according to any one of statements 1 to 44, wherein R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0354] 46. The compound according to any one of statements 1 to 45, wherein R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a C.sub.3-7cycloalkyl or a C.sub.5-7cycloalkylene. [0355] 47. The compound according to any one of statements 1 to 43, wherein R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl or a C.sub.5-6cycloalkylene. [0356] 48. The compound according to any one of statements 1 to 47, wherein R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl. [0357] 49. The compound according to any one of statements 1 to 48, wherein R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a C.sub.3-5cycloalkyl. [0358] 50. The compound according to any one of statements 1 to 49, wherein R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyano C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0359] 51. The compound according to any one of statements 1 to 50, wherein R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0360] 52. The compound according to any one of statements 1 to 51, wherein R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0361] 53. The compound according to any one of statements 1 to 52, wherein R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0362] 54. The compound according to any one of statements 1 to 53, wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, [0363] C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0364] 55. The compound according to any one of statements 1 to 54, wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0365] 56. The compound according to any one of statements 1 to 55, wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0366] 57. The compound according to any one of statements 1 to 56, wherein R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0367] 58. The compound according to any one of statements 1 to 57, wherein R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a C.sub.3-7cycloalkyl or a C.sub.5-7cycloalkylene. [0368] 59. The compound according to one of statements 1 to 58, wherein R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl or a C.sub.5-6cycloalkylene. [0369] 60. The compound according to any one of statements 1 to 59, wherein R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl. [0370] 61. The compound according to any one of statements 1 to 60, wherein R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a C.sub.3-5cycloalkyl. [0371] 62. The compound according to any one of statements 1 to 61, wherein R.sup.8 is hydrogen. [0372] 63. The compound according to any one of statements 1 to 62, wherein q is 1. [0373] 64. The compound according to any one of statements 1 to 63, wherein R.sup.9 is selected from the group consisting hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyano C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6 alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8 cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0374] 65. The compound according to any one of statements 1 to 64, wherein R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0375] 66. The compound according to any one of statements 1 to 65, wherein R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0376] 67. The compound according to any one of statements 1 to 66, wherein R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0377] 68. The compound according to any one of statements 1 to 67, wherein R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0378] 69. The compound according to any one of statements 1 to 68, wherein R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0379] 70. The compound according to any one of statements 1 to 69, wherein R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0380] 71. The compound according to any one of statements 1 to 70, wherein R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0381] 72. The compound according to any one of statements 1 to 71, wherein R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a C.sub.3-7cycloalkyl or a C.sub.5-7cycloalkylene. [0382] 73. The compound according to any one of statements 1 to 72, wherein R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl or a C.sub.5-6cycloalkylene. [0383] 74. The compound according to any one of statements 1 to 73, wherein R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl. [0384] 75. The compound according to any one of statements 1 to 74, wherein R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a C.sub.3-5 cycloalkyl. [0385] 76. The compound according to any one of statements 1 to 75, wherein L.sup.2 is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q. [0386] 77. The compound according to any one of statements 1 to 76, wherein L.sup.2 is SO.sub.2. [0387] 78. The compound according to any one of statements 1 to 77, wherein L.sup.2 is (CR.sup.9R.sup.10).sub.q. [0388] 79. The compound according to any one of statements 1 to 78, wherein L.sup.3 is a single bond or is selected from the group consisting of (CR.sup.11R.sup.12).sub.r, O, NH, and N(C.sub.1-6alkyl)-. [0389] 80. The compound according to any one of statements 1 to 79, wherein L.sup.3 is a single bond or is selected from the group consisting of (CR.sup.11R.sup.12).sub.r, and O. [0390] 81. The compound according to any one of statements 1 to 80, wherein L.sup.3 is a single bond or is (CR.sup.11R.sup.12).sub.r. [0391] 82. The compound according to any one of statements 1 to 81, wherein r is 1. [0392] 83. The compound according to any one of statements 1 to 82, wherein L.sup.3 is a single bond. [0393] 84. The compound according to any one of statements 1 to 83, wherein R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-Rarylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0394] 85. The compound according to any one of statements 1 to 84, wherein R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0395] 86. The compound according to any one of statements 1 to 85, wherein R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0396] 87. The compound according to any one of statements 1 to 86, wherein R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0397] 88. The compound according to any one of statements 1 to 87, wherein R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0398] 89. The compound according to any one of statements 1 to 88, wherein R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0399] 90. The compound according to any one of statements 1 to 89, wherein R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0400] 91. The compound according to any one of statements 1 to 90, wherein R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy. [0401] 92. The compound according to any one of statements 1 to 91, wherein R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a C.sub.3-7cycloalkyl or a C.sub.5-7cycloalkylene. [0402] 93. The compound according to any one of statements 1 to 92, wherein R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl or a C.sub.5-6cycloalkylene. [0403] 94. The compound according to any one of statements 1 to 93, wherein R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a C.sub.3-6cycloalkyl. [0404] 95. The compound according to any one of statements 1 to 94, wherein R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a C.sub.3-5 cycloalkyl. [0405] 96. The compound according to any one of statements 1 to 95, wherein R.sup.13 is hydrogen. [0406] 97. The compound according to any one of statements 1 to 96, wherein each R.sup.15 independently selected from the group consisting of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, or S(O).sub.2. [0407] 98. The compound according to any one of statements 1 to 97, wherein each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyano C.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0408] 99. The compound according to any one of statements 1 to 98, wherein each R.sup.15 is independently selected from C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12aryl C.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO; [0409] 100. The compound according to any one of statements 1 to 99, wherein each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0410] 101. The compound according to any one of statements 1 to 100, wherein each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0411] 102. The compound according to any one of statements 1 to 101, wherein each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1. [0412] 103. The compound according to any one of statements 1 to 102, wherein R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, or S(O).sub.2. [0413] 104. The compound according to any one of statements 1 to 103, wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0414] 105. The compound according to any one of statements 1 to 104, wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0415] 106. The compound according to any one of statements 1 to 105, wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6 alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0416] 107. The compound according to any one of statements 1 to 106, wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO. [0417] 108. The compound according to any one of statements 1 to 107, wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, heterocyclyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2. [0418] 109. The compound according to any one of statements 1 to 108, wherein each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or S(O).sub.2. [0419] 110. The compound according to any one of statements 1 to 109, wherein each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0420] 111. The compound according to any one of statements 1 to 110, wherein each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, or heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0421] 112. The compound according to any one of statements 1 to 111, wherein each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0422] 113. The compound according to any one of statements 1 to 112, wherein each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0423] 114. The compound according any one of statements 1 to 113, wherein each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, and heteroaryl. [0424] 115. The compound according to any one of statements 1 to 114, wherein each R.sup.15 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or S(O).sub.2. [0425] 116. The compound according to any one of statements 1 to 115, wherein each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0426] 117. The compound according to any one of statements 1 to 116, wherein each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, or heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0427] 118. The compound according to any one of statements 1 to 117, wherein each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0428] 119. The compound according to any one of statements 1 to 118, wherein each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0429] 120. The compound according to any one of statements 1 to 119, wherein each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, and heteroaryl. 121. The compound according to any one of statements 1 to 120, wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-, or 6-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO, or NO. [0430] 122. The compound according to any one of statements 1 to 121, wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-membered heterocyclyl; and wherein at least one carbon atom of said heterocyclyl can be oxidized to form at least one CO. [0431] 123. The compound according to any one of statements 1 to 122, wherein each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or S(O).sub.2. [0432] 124. The compound according to any one of statements 1 to 123, wherein each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0433] 125. The compound according to any one of statements 1 to 124, wherein each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, or heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0434] 126. The compound according to any one of statements 1 to 125, wherein each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0435] 127. The compound according to any one of statements 1 to 126, wherein each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0436] 128. The compound according to any one of statements 1 to 127, wherein each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, heterocyclyl, and heteroaryl. [0437] 129. The compound according to any one of statements 1 to 128, wherein each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or S(O).sub.2. [0438] 130. The compound according to any one of statements 1 to 129, wherein each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0439] 131. The compound according to any one of statements 1 to 130, wherein each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cyclo alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, or heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0440] 132. The compound according to any one of statements 1 to 131, wherein each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0441] 133. The compound according to any one of statements 1 to 132, wherein each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, and heteroaryl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-8cycloalkyl, heterocyclyl, or heteroaryl can be oxidized to form at least one CO. [0442] 134. The compound according to any one of statements 1 to 133, wherein each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl. [0443] 135. The compound according to any one of statements 1 to 134, wherein each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene*, and heteroaryleneC.sub.1-6alkylene*; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene, or heteroaryleneC.sub.1-6alkylene can be oxidized to form at least one CO, or S(O).sub.2, wherein * represents where R.sup.21 is bound to CO. [0444] 136. The compound according to any one of statements 1 to 135, wherein R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, C.sub.6-12arylene, and C.sub.3-8cycloalkylene; and wherein at least one carbon atom of said C.sub.1-6alkylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene can be oxidized to form at least one CO. [0445] 137. The compound according to any one of statements 1 to 136, wherein each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, and C.sub.3-8cycloalkylene; and wherein at least one carbon atom of said C.sub.1-6alkylene, C.sub.3-8cycloalkylene can be oxidized to form at least one CO. [0446] 138. The compound according to any one of statements 1 to 137, wherein each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, and C.sub.3-8cycloalkylene; and wherein at least one carbon atom of said C.sub.1-6alkylene, C.sub.3-8cycloalkylene can be oxidized to form at least one CO. [0447] 139. The compound according to any one of statements 1 to 138, wherein each R.sup.21 is C.sub.1-6alkylene. [0448] 140. The compound according to any one of statements 1 to 139, wherein each R.sup.21 is C.sub.1-4alkylene. [0449] 141. The compound according to any one of statements 1 to 140, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroaryl C.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.2-6alkenyl, CO.sub.2C.sub.2-6alkynyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2C.sub.6-12arylC.sub.1-6alkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, CO.sub.2heterocyclylC.sub.1-6alkyl, CO.sub.2heteroarylC.sub.1-6alkyl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.2-6alkenyl, C(O)NHC.sub.2-6alkynyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NH(C.sub.6-12arylC.sub.1-6alkyl), C(O)NH-heterocyclyl, C(O)NH-heteroaryl, C(O)NH(heterocyclylC.sub.1-6alkyl), C(O)NH(heteroarylC.sub.1-6alkyl), COH, C(O)C.sub.1-6alkyl, C(O)C.sub.2-6alkenyl, C(O)C.sub.2-6alkynyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O)OH, S(O)C.sub.1-6alkyl, S(O)C.sub.2-6alkenyl, S(O)C.sub.2-6alkynyl, S(O)C.sub.6-12aryl, S(O)C.sub.3-8cycloalkyl, S(O)heterocyclyl, S(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.2-6alkenyl, S(O).sub.2C.sub.2-6alkynyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2C.sub.6-12arylC.sub.1-6alkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2heterocyclylC.sub.1-6alkyl, S(O).sub.2heteroarylC.sub.1-6alkyl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.2-6alkenyl, S(O).sub.2NHC.sub.2-6alkynyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, S(O).sub.2NH(C.sub.6-12arylC.sub.1-6alkyl), S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, S(O).sub.2NH(heterocyclylC.sub.1-6alkyl), S(O).sub.2NH(heteroarylC.sub.1-6alkyl), nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.2-6alkenyl, NHC(O)C.sub.2-6alkynyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, C.sub.1-6alkylene-C(O)NH.sub.2, C.sub.1-6alkylene-C(O)NHC.sub.1-6alkyl, C.sub.1-6alkyleneC(O)NHC.sub.2-6alkenyl, C.sub.1-6alkyleneC(O)NHC.sub.2-6alkynyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12aryl, C.sub.1-6alkyleneC(O)NHC.sub.3-8cyclo alkyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12arylC.sub.1-6alkyl, C.sub.1-6alkyleneC(O)NHheterocyclyl, C.sub.1-6alkyleneC(O)NHheteroaryl, C.sub.1-6alkyleneC(O)NH-heterocyclylC.sub.1-6alkyl, C.sub.1-6alkylene-C(O)NH-heteroarylC.sub.1-6alkyl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.2-6alkenyl, NHS(O).sub.2C.sub.2-6alkynyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cyclo alkyl, NHS(O).sub.2C.sub.6-12arylC.sub.1-6alkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NHS(O).sub.2heterocyclylC.sub.1-6alkyl, NHS(O).sub.2heteroarylC.sub.1-6alkyl, N(C.sub.1-6alkyl) S(O).sub.2H, N(C.sub.1-6alkyl)S(O).sub.2OH, N(C.sub.1-6alkyl) S(O).sub.2C.sub.1-6alkyl, N(C.sub.1-6alkyl)S(O).sub.2C.sub.2-6alkenyl, N(C.sub.1-6alkyl)S(O).sub.2C.sub.2-6alkynyl, N(C.sub.1-6alkyl)S(O).sub.2C.sub.6-12aryl, N(C.sub.1-6alkyl)S(O).sub.2C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl) S(O).sub.2C.sub.6-12arylC.sub.1-6alkyl, N(C.sub.1-6alkyl) S(O).sub.2heterocyclyl, N(C.sub.1-6alkyl) S(O).sub.2heteroaryl, N(C.sub.1-6alkyl) S(O).sub.2heterocyclylC.sub.1-6alkyl, N(C.sub.1-6alkyl)S(O).sub.2heteroarylC.sub.1-6alkyl, NHC(O)NH.sub.2, NHC(O)NHC.sub.1-6alkyl, NHC(O)NHC.sub.2-6alkenyl, NHC(O)NHC.sub.2-6alkynyl, NHC(O)NHC.sub.6-12aryl, NHC(O)NHC.sub.3-8cycloalkyl, NHC(O)NHC.sub.6-12arylC.sub.1-6alkyl, NHC(O)NH-heterocyclyl, NHC(O)NH-heteroaryl, NHC(O)NHheterocyclylC.sub.1-6alkyl, NHC(O)NHheteroarylC.sub.1-6alkyl, NHC(O)NC.sub.1-6alkylC.sub.1-6alkyl, NHC(O)NC.sub.1-6alkylC.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)NHC.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)NHC.sub.2-6alkenyl, N(C.sub.1-6alkyl)C(O)NHC.sub.2-6alkynyl, N(C.sub.1-6alkyl) C(O)NHC.sub.6-12aryl, N(C.sub.1-6alkyl) C(O)NHC.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)NHC.sub.6-12arylC.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)NHheterocyclyl, N(C.sub.1-6alkyl)C(O)NHheteroaryl, N(C.sub.1-6alkyl)C(O)NHheterocyclylC.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)NHheteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0450] 142. The compound according to any one of statements 1 to 141, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12 arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NH-heterocyclyl, C(O)NH-heteroaryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O)OH, S(O)C.sub.1-6alkyl, S(O)C.sub.6-12aryl, S(O)C.sub.3-8cycloalkyl, S(O)heterocyclyl, S(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cyclo alkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cyclo alkyl, S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, C.sub.1-6alkylene-C(O)NH.sub.2, C.sub.1-6alkyleneC(O)NHC.sub.1-6alkyl, C.sub.1-6alkylene-C(O)NHC.sub.6-12aryl, C.sub.1-6alkyleneC(O)NHC.sub.3-8cyclo alkyl, C.sub.1-6alkyleneC(O)NHheterocyclyl, C.sub.1-6alkylene-C(O)NHheteroaryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, NC.sub.1-6alkylS(O).sub.2heteroaryl, NHC(O)NH.sub.2, NHC(O)NHC.sub.1-6alkyl, NHC(O)NHC.sub.6-12aryl, NHC(O)NHC.sub.3-8cycloalkyl, NHC(O)NHC.sub.6-12arylC.sub.1-6alkyl, NHC(O)NH-heterocyclyl, NHC(O)NHheteroaryl, NC.sub.1-6alkylC(O)NHC.sub.1-6alkyl, NC.sub.1-6alkylC(O)NHC.sub.6-12aryl, NC.sub.1-6alkylC(O)NHC.sub.3-8cycloalkyl, NC.sub.1-6alkylC(O)NHheterocyclyl, and NC.sub.1-6alkylC(O)NHheteroaryl. [0451] 143. The compound according to any one of statements 1 to 142, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NHheterocyclyl, C(O)NHheteroaryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, C.sub.1-6alkyleneC(O)NH.sub.2, C.sub.1-6alkyleneC(O)NHC.sub.1-6alkyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12aryl, C.sub.1-6alkyleneC(O)NHC.sub.3-8cycloalkyl, C.sub.1-6alkyleneC(O)NH-heterocyclyl, C.sub.1-6alkyleneC(O)NHheteroaryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NC.sub.1-6alkyl S(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkyl S(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkyl S(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, and NC.sub.1-6alkyl S(O).sub.2heteroaryl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0452] 144. The compound according to any one of statements 1 to 143, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cyclo alkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NHheterocyclyl, C(O)NHheteroaryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkyl S(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, and NC.sub.1-6alkylS(O).sub.2heteroaryl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0453] 145. The compound according to any one of statements 1 to 144, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12 cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.1-12aryloxy, heterocyclyloxy, heteroaryloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, and NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0454] 146. The compound according to any one of statements 1 to 145, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, and NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl; and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0455] 147. The compound according to any one of statements 1 to 146, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12 cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, heteroaryl, hydroxyl, C.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di C.sub.1-6alkylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, COH, C(O)C.sub.1-6alkyl, NHC(O)H, NHC(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)H, and N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0456] 148. The compound according to any one of statements 1 to 147, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di C.sub.1-6alkylamino, C(O)C.sub.1-6alkyl, NHC(O)C.sub.1-6alkyl, and N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0457] 149. The compound according to any one of statements 1 to 148, wherein each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, and mono or di-C.sub.1-6alkylamino; and wherein at least one carbon atom of said C.sub.1-6alkyl, C.sub.6-12aryl, heterocyclyl, heteroaryl, can be oxidized to form at least one CO. [0458] 150. The compound according to any one of statements 1 to 149, wherein two Z.sup.1 together with the atom to which they are attached form a 5-, or 6-membered ring; and wherein at least one carbon atom of said ring can be oxidized to form at least one CO. [0459] 151. The compound according to any one of statements 1 to 150, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroaryl C.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.2-6alkenyl, CO.sub.2C.sub.2-6alkynyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2C.sub.6-12arylC.sub.1-6alkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, CO.sub.2heterocyclylC.sub.1-6alkyl, CO.sub.2heteroarylC.sub.1-6alkyl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.2-6alkenyl, C(O)NHC.sub.2-6alkynyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NH(C.sub.6-12arylC.sub.1-6alkyl), C(O)NH-heterocyclyl, C(O)NH-heteroaryl, C(O)NH(heterocyclylC.sub.1-6alkyl), C(O)NH(heteroarylC.sub.1-6alkyl), COH, C(O)C.sub.1-6alkyl, C(O)C.sub.2-6alkenyl, C(O)C.sub.2-6alkynyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O)OH, S(O)C.sub.1-6alkyl, S(O)C.sub.2-6alkenyl, S(O)C.sub.2-6alkynyl, S(O)C.sub.6-12aryl, S(O)C.sub.3-8cycloalkyl, S(O)heterocyclyl, S(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.2-6alkenyl, S(O).sub.2C.sub.2-6alkynyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2C.sub.6-12arylC.sub.1-6alkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2heterocyclylC.sub.1-6alkyl, S(O).sub.2heteroarylC.sub.1-6alkyl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.2-6alkenyl, S(O).sub.2NHC.sub.2-6alkynyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, S(O).sub.2NH(C.sub.6-12arylC.sub.1-6alkyl), S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, S(O).sub.2NH(heterocyclylC.sub.1-6alkyl), S(O).sub.2NH(heteroarylC.sub.1-6alkyl), nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.2-6alkenyl, NHC(O)C.sub.2-6alkynyl, NHC(O)C.sub.6-12aryl, NHC(O) C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, C.sub.1-6alkyl e C(O)NH.sub.2, C.sub.1-6alkyleneC(O)NHC.sub.1-6alkyl, C.sub.1-6alkylene-C(O)NHC.sub.2-6alkenyl, C.sub.1-6alkyleneC(O)NHC.sub.2-6alkynyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12aryl, C.sub.1-6alkylene-C(O)NHC.sub.3-8cycloalkyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12arylC.sub.1-6alkyl, C.sub.1-6alkyleneC(O)NHheterocyclyl, C.sub.1-6alkyleneC(O)NHheteroaryl, C.sub.1-6alkyleneC(O)NHheterocyclylC.sub.1-6alkyl, C.sub.1-6alkylene-C(O)NHheteroarylC.sub.1-6alkyl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.2-6alkenyl, NHS(O).sub.2C.sub.2-6alkynyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2C.sub.6-12arylC.sub.1-6alkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NHS(O).sub.2heterocyclylC.sub.1-6alkyl, NHS(O).sub.2heteroarylC.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.2-6alkenyl, NC.sub.1-6alkylS(O).sub.2C.sub.2-6alkynyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12arylC.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, NC.sub.1-6alkyl S(O).sub.2heteroaryl, NC.sub.1-6alkylS(O).sub.2heterocyclylC.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2heteroarylC.sub.1-6alkyl, NHC(O)NH.sub.2, NHC(O)NHC.sub.1-6alkyl, NHC(O)NHC.sub.2-6alkenyl, NHC(O)NHC.sub.2-6alkynyl, NHC(O)NHC.sub.6-12aryl, NHC(O)NHC.sub.3-8cycloalkyl, NHC(O)NHC.sub.6-12arylC.sub.1-6alkyl, NHC(O)NH-heterocyclyl, NHC(O)NH-heteroaryl, NHC(O)NHheterocyclylC.sub.1-6alkyl, NHC(O)NHheteroarylC.sub.1-6alkyl, NHC(O)NC.sub.1-6alkylC.sub.1-6alkyl, NHC(O)NC.sub.1-6alkylC.sub.6-12aryl, NC.sub.1-6alkylC(O)NHC.sub.1-6alkyl, NC.sub.1-6alkylC(O)NHC.sub.2-6alkenyl, NC.sub.1-6alkylC(O)NHC.sub.2-6alkynyl, NC.sub.1-6alkylC(O)NHC.sub.6-12aryl, NC.sub.1-6alkylC(O)NHC.sub.3-8cycloalkyl, NC.sub.1-6alkylC(O)NHC.sub.6-12arylC.sub.1-6alkyl, NC.sub.1-6alkylC(O)NHheterocyclyl, NC.sub.1-6alkylC(O)NHheteroaryl, NC.sub.1-6alkylC(O)NHheterocyclylC.sub.1-6alkyl, and NC.sub.1-6alkylC(O)NHheteroarylC.sub.1-6alkyl; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0460] 152. The compound according to any one of statements 1 to 151, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.2-6alkenyloxy, C.sub.2-6alkynyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.2-6alkenylthio, C.sub.2-6alkynylthio, C.sub.6-12arylthio, C.sub.3-8cyclo alkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclyl amino, mono or di-heteroaryl amino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NH-heterocyclyl, C(O)NHheteroaryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O)OH, S(O)C.sub.1-6alkyl, S(O)C.sub.6-12aryl, S(O)C.sub.3-8cycloalkyl, S(O)heterocyclyl, S(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cyclo, S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cyclo alkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl) C(O)heteroaryl, C.sub.1-6alkylene C(O)NH.sub.2, C.sub.1-6alkyleneC(O)NHC.sub.1-6alkyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12aryl, C.sub.1-6alkyleneC(O)NHC.sub.3-8cycloalkyl, C.sub.1-6alkyleneC(O)NHheterocyclyl, C.sub.1-6alkyleneC(O)NHheteroaryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, NC.sub.1-6alkylS(O).sub.2heteroaryl, NHC(O)NH.sub.2, NHC(O)NHC.sub.1-6alkyl, NHC(O)NHC.sub.6-12aryl, NHC(O)NHC.sub.3-8cycloalkyl, NHC(O)NHC.sub.6-12arylC.sub.1-6alkyl, NHC(O)NH-heterocyclyl, NHC(O)NHheteroaryl, NC.sub.1-6alkylC(O)NHC.sub.1-6alkyl, NC.sub.1-6alkylC(O)NHC.sub.6-12aryl, NC.sub.1-6alkylC(O)NHC.sub.3-8cycloalkyl, NC.sub.1-6alkylC(O)NHheterocyclyl, and NC.sub.1-6alkylC(O)NHheteroaryl; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0461] 153. The compound according to any one of statements 1 to 152, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, C.sub.6-12arylC.sub.1-6alkylthio, heterocyclylthio, heteroarylthio, heterocyclylC.sub.1-6alkylthio, heteroarylC.sub.1-6alkylthio, cyanoC.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NHheterocyclyl, C(O)NHheteroaryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, C.sub.1-6alkyleneC(O)NH.sub.2, C.sub.1-6alkyleneC(O)NHC.sub.1-6alkyl, C.sub.1-6alkyleneC(O)NHC.sub.6-12aryl, C.sub.1-6alkyleneC(O)NHC.sub.3-8cycloalkyl, C.sub.1-6alkyleneC(O)NH-heterocyclyl, C.sub.1-6alkyleneC(O)NHheteroaryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, and NC.sub.1-6alkylS(O).sub.2heteroaryl; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. 154. The compound according to any one of statements 1 to 153, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cyclo alkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, C.sub.3-12cycloalkyloxy, C.sub.6-12arylC.sub.1-6alkyloxy, heterocyclyloxy, heteroaryloxy, heterocyclylC.sub.1-6alkyloxy, heteroarylC.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, C.sub.6-12arylthio, C.sub.3-8cycloalkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, mono or di-heterocyclylamino, mono or di-heteroarylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, CO.sub.2heterocyclyl, CO.sub.2heteroaryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, C(O)NH-heterocyclyl, C(O)NHheteroaryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, C(O)heterocyclyl, C(O)heteroaryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2heterocyclyl, S(O).sub.2heteroaryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, S(O).sub.2NHheterocyclyl, S(O).sub.2NHheteroaryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, NHC(O)heterocyclyl, NHC(O)heteroaryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl) C(O)heterocyclyl, N(C.sub.1-6alkyl)C(O)heteroaryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NHS(O).sub.2heterocyclyl, NHS(O).sub.2heteroaryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2heterocyclyl, and NC.sub.1-6alkylS(O).sub.2heteroaryl; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, or NO. [0462] 155. The compound according to any one of statements 1 to 154, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroaryl C.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, heterocyclyloxy, heteroaryloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, mono or di-C.sub.3-8cycloalkylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, CO.sub.2C.sub.3-8cycloalkyl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, C(O)NHC.sub.3-8cycloalkyl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, C(O)C.sub.3-8cycloalkyl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2C.sub.3-8cycloalkyl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, S(O).sub.2NHC.sub.3-8cycloalkyl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, NHC(O)C.sub.3-8cycloalkyl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)C.sub.3-8cycloalkyl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NHS(O).sub.2C.sub.3-8cycloalkyl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl, and NC.sub.1-6alkylS(O).sub.2C.sub.3-8cycloalkyl; and wherein at least one carbon atom said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0463] 156. The compound according to any one of statements 1 to 155, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, C.sub.6-12aryloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, mono or di-C.sub.6-12arylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, CO.sub.2C.sub.6-12aryl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, C(O)NHC.sub.6-12aryl, COH, C(O)C.sub.1-6alkyl, C(O)C.sub.6-12aryl, S(O).sub.2OH, S(O).sub.2C.sub.1-6alkyl, S(O).sub.2C.sub.6-12aryl, S(O).sub.2NH.sub.2, S(O).sub.2NHC.sub.1-6alkyl, S(O).sub.2NHC.sub.6-12aryl, nitro, NHC(O)H, NHC(O)C.sub.1-6alkyl, NHC(O)C.sub.6-12aryl, N(C.sub.1-6alkyl)C(O)H, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.6-12aryl, NHS(O).sub.2H, NHS(O).sub.2OH, NHS(O).sub.2C.sub.1-6alkyl, NHS(O).sub.2C.sub.6-12aryl, NC.sub.1-6alkylS(O).sub.2H, NC.sub.1-6alkylS(O).sub.2OH, NC.sub.1-6alkylS(O).sub.2C.sub.1-6alkyl, and NC.sub.1-6alkylS(O).sub.2C.sub.6-12aryl; and wherein at least one carbon atom of said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0464] 157. The compound according to any one of statements 1 to 156, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, cyanoC.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, CO.sub.2H, CO.sub.2C.sub.1-6alkyl, C(O)NH.sub.2, C(O)NHC.sub.1-6alkyl, COH, C(O)C.sub.1-6alkyl, NHC(O)H, NHC(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)H, and N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl; and wherein at least one carbon atom of said ring, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO. [0465] 158. The compound according to any one of statements 1 to 157, wherein each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, C.sub.1-6alkyloxy, thiol, C.sub.1-6alkylthio, cyano, amino, mono or di-C.sub.1-6alkylamino, C(O)C.sub.1-6alkyl, NHC(O)C.sub.1-6alkyl, N(C.sub.1-6alkyl)C(O)C.sub.1-6alkyl. [0466] 159. The compound according to any one of statements 1 to 158, wherein two Z.sup.2 together with the atom to which they are attached form a 5-, or 6-membered ring; and wherein at least one carbon atom of said ring can be oxidized to form at least one CO. [0467] 160. The compound according to any one of statements 1 to 159, wherein L.sup.5 is a single bond. [0468] 161. The compound according to any one of statements 1 to 160, wherein L.sup.5 is CO. [0469] 162. The compound according to any one of statements 1 to 161, having structural formula (IIJ),

##STR00015## [0470] wherein, L.sup.1, n, R.sup.1, R.sup.2, and R.sup.3 have the same meaning as defined in any one of statements 1 to 159. [0471] 163. The compound according to any one of statements 1 to 162, having structural formula (IIK),

##STR00016## [0472] wherein, L.sup.1, n, R.sup.1, R.sup.3, and Z.sup.1 have the same meaning as defined in any one of statements 1 to 160, and wherein, w is an integer selected from 1, 2, or 3. [0473] 164. The compound according to any one of statements 1 to 163, having structural formula (IJ) or (IIL),

##STR00017## [0474] wherein, L.sup.1, L.sup.3, L.sup.5, n, R.sup.1, R.sup.2, and R.sup.3 have the same meaning as defined in any one of statements 1 to 163. [0475] 165. The compound according to any one of statements 1 to 164, wherein L.sup.2 is a single bond, and L.sup.3 is selected from the group consisting of CH.sub.2, CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2CH.sub.2. [0476] 166. The compound according to any one of statements 1 to 165, wherein L.sup.2 is a single bond, and L.sup.3 is CH.sub.2CH.sub.2. [0477] 167. The compound according to any one of statements 1 to 166, wherein L.sup.3 is a single bond, and L.sup.2 is selected from the group consisting of CH.sub.2, CH.sub.2CH.sub.2, and CH.sub.2CH.sub.2CH.sub.2. [0478] 168. The compound according to any one of statements 1 to 167, wherein L.sup.3 is a single bond, and L.sup.2 is CH.sub.2CH.sub.2. [0479] 169. The compound according to any one of statements 1 to 168, selected from the group consisting of 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 4-(2-(4-(3-Phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 5-(4-Isopentylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorobenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-(Oxazol-5-yl)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 3-(p-Tolyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Fluorophenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-((4-Isopropylphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 3-(p-Tolyl)-5-(4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(4-((4-(3-(p-Tolyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenyl)pyrrolidin-2-one; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(4-chlorophenyl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; 3-(3-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; 2-((4-(3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; 3-(3-Fluorophenyl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; 3-(3-Fluorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-(3-Fluorophenyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,4-difluorophenyl)-1,2,4-oxadiazole; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-Benzo[1,3]dioxol-5-ylmethyl-4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(2-methyl-benzyl)-piperazine; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-((4-(3-Benzyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-((S)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Methoxy-benzenesulfonyl)-4-[3-((R)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-Benzo[1,3]dioxol-5-ylmethyl-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-((4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(4-chloro-phenyl)-ethyl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; 3-(4-Chlorobenzyl)-5-(4-(2-fluorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(2-Chloro-benzyl)-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methyl-benzyl)-piperazine; 4-{4-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-butyronitrile; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-ethoxy-ethyl)-piperazine; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-propyl-piperazine; 3-(4-Chlorobenzyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4,4,4-trifluoro-butyl)-piperazine; 3-(4-Chlorobenzyl)-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-(4-Chlorobenzyl)-5-(4-isopropylpiperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 5-{4-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-3H-benzooxazol-2-one; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-dimethylpiperazine-1-sulfonamide; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-diethylpiperazine-1-sulfonamide; 4-((4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)morpholine; 3-(3-Chlorobenzyl)-5-(4-(pyrrolidin-1-ylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(Azepan-1-ylsulfonyl)piperazin-1-yl)-3-(3-chlorobenzyl)-1,2,4-oxadiazole; 3-(3-Chlorobenzyl)-5-(4-((4-methoxypiperidin-1-yl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Fluoro-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; N-(4-{4-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-phenyl)-acetamide; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-methyl-benzyl)-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-isopropoxy-benzenesulfonyl)-piperazine; 3-(4-((4-(3-(3-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenoxy)propanenitrile; 1-(2,3-Dihydro-benzofuran-5-sulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-(3-Fluorobenzyl)-5-(4-((4-isopropoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(4-Chloro-benzyl)-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-(4-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 1-(4-Methylsulfanyl-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 4-(2-(4-(3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 5-(4-Isopentylpiperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(difluoro(4-fluorophenyl)methyl)-1,2,4-oxadiazole; 3-(Difluoro(4-fluorophenyl)methyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-(Cyclopropylmethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Cyclopropylmethyl)-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-Ethoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(2-methyl-pyridin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-((2-methylpyridin-4-yl)methyl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 2-((4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; 5-(4-Isopentylpiperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 4-(2-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 4-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)butanenitrile; 5-(4-((6-Methylpyridin-2-yl)methyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-chlorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-chlorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; 4-(2-(4-(3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclopropyl-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2-(2-methylpyridin-4-yl)propan-2-yl)-1,2,4-oxadiazole; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; (5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol; 3-(Methoxymethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((4-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-((3-Chlorophenoxy)methyl)-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(phenoxymethyl)-1,2,4-oxadiazole; 3-((Cyclopropylmethoxy)methyl)-5-(4-(4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-((pyridin-3-yloxy)methyl)-1,2,4-oxadiazole; 4-((5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methoxy)benzonitrile; 3-((4-Fluorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-propyl-1,2,4-oxadiazole; 3-Butyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(Tert-butyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Cyclohexyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-Isopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-Methoxyethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; 5-(7-((4-Methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-(Methylthio)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-Ethoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; 5-(7-((4-(Difluoromethoxy)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; (3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methanone; 3-(4-Fluorobenzyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; 3-(2-Methoxyethyl)-5-(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; and a solvate, hydrate, pharmaceutically acceptable salt thereof. [0480] 170. A pharmaceutical composition comprising one or more pharmaceutically excipients and a therapeutically effective amount of a compound according to any one of statements 1 to 169; or a therapeutically effective amount of a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof. [0481] 171. A compound according to any one of statements 1 to 169 or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition according to statement 170, for use as a medicament. [0482] 172. A compound according to any one of statements 1 to 169, or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition according to statement 170, for use as a medicine for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases and/or protein misfolding disorders. [0483] 173. A compound according to any one of statements 1 to 169, or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition according to statement 170, for use as a medicine for the prevention and/or treatment of diabetes mellitus, Parkinson's disease, Alzheimer's disease, diffuse Lewy body disease, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy, Huntington's disease, frontotemporal lobar degeneration (FTLD), cystic fibrosis, Creutzfeld-Jacob's disease, impaired glucose tolerance, hyperglycemia, hypoglycemia, glyceraldehyde-3-phosphate dehydrogenase deficiency, hyperinsulinism, impaired insulin production, impaired insulin sensitivity, metabolic syndrome, insulin resistance syndrome, obesity, lipidoses, cardiac lipidoses, dyslipidemia, fatty liver, lipodistrophy, cardiovascular diseases and hypertension. [0484] 174. A compound according to any one of statements 1 to 169, or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition according to statement 170, for use as a medicine for the prevention and/or treatment of diabetes mellitus, Parkinson's disease and/or Alzheimer's disease. [0485] 175. A compound according to any one of statements 1 to 169, having one of formula (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IF), (IIF), (IH), (IIH), (IIK), for use as a medicine for the prevention and/or treatment of diabetes mellitus, and/or Parkinson's disease. [0486] 176. A compound according to any one of statements 1 to 169, having one of formula (I), (II), (IE), (IIE), (IG), (IIG), wherein L.sup.2 is a single bond or is (CR.sup.9R.sup.10).sub.q; (IJ) or (IIL); for use as a medicine for the prevention and/or treatment of Alzheimer's disease. [0487] 177. A compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170, for use as a medicine for the prevention and/or treatment of -diabetes mellitus type 1, diabetes mellitus type 2, Parkinson's disease and/or Alzheimer's disease. [0488] 178. A compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170, or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; for use as a medicine for the prevention and/or treatment of diabetes mellitus type 2, Parkinson's disease and/or Alzheimer's disease. [0489] 179. A method of prevention and/or treatment of metabolic disorders, and/or neurodegenerative diseases, and/or protein misfolding disorders, comprising administering an effective amount of a compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170; or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl) ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof to a subject in need thereof. [0490] 180. A method of prevention and/or treatment of diabetes mellitus, Parkinson's disease, Alzheimer's disease, diffuse Lewy body disease, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy, Huntington's disease, frontotemporal lobar degeneration (FTLD), cystic fibrosis, Creutzfeld-Jacob's disease, impaired glucose tolerance, hyperglycemia, hypoglycemia, glyceraldehyde-3-phosphate dehydrogenase deficiency, hyperinsulinism, impaired insulin production, impaired insulin sensitivity, metabolic syndrome, insulin resistance syndrome, obesity, lipidoses, cardiac lipidoses, dyslipidemia, fatty liver, lipodistrophy, cardiovascular diseases and hypertension, comprising administering an effective amount of a compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170; or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof; to a subject in need thereof. [0491] 181. A method of prevention and/or treatment of diabetes mellitus, Parkinson's disease and/or Alzheimer's disease, comprising administering an effective amount of a compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170; or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof to a subject in need thereof. [0492] 182. A method of prevention and/or treatment of diabetes mellitus type 1, diabetes mellitus type 2, Parkinson's disease and/or Alzheimer's disease, comprising administering an effective amount of a compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170; or a compound selected from the group consisting of 5-(4-(3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof to a subject in need thereof. [0493] 183. A method of prevention and/or treatment of diabetes mellitus type 2, Parkinson's disease and/or Alzheimer's disease, comprising administering an effective amount of a compound according to any one of statements 1 to 169, or a pharmaceutical composition according to statement 170; or a compound selected from the group consisting of 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 2-(4-(3-(3,5-dichlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)-1-morpholinoethanone; 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole, and a solvate, hydrate, or pharmaceutically acceptable salt thereof to a subject in need thereof. [0494] 184. A method of prevention and/or treatment of diabetes mellitus, and/or Parkinson's disease, comprising administering an effective amount of a compound according to any one of statements 1 to 169, having one of formula (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (HD), (IF), (IIF), (IH), (IIH), or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof to a subject in need thereof. [0495] 185. The compound according to any one of statements 1 to 168, wherein the group heteroaryl is selected from a group comprising 5 to 12 carbon-atom aromatic rings or ring systems containing 1 or 2 rings which can be fused together or linked covalently, typically containing 5 to 6 atoms; at least one of which is aromatic in which one or more carbon atoms in one or more of these rings can be replaced by N, O and/or S atoms where the N and S heteroatoms may optionally be oxidized and the N heteroatoms may optionally be quaternized, wherein said rings may be fused to an aryl, cycloalkyl, heteroaryl or heterocyclyl ring; and wherein at least one carbon atom of said heteroaryl can be oxidized to form at least one CO. [0496] 186. The compound according to any one of statements 1 to 168, and 185, wherein the group heteroaryl is selected from the group comprising pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazinyl, dioxinyl, thiazinyl, triazinyl, imidazo[2,1-b][1,3]thiazolyl, thieno[3,2-b]furanyl, thieno[3,2-b]thiophenyl, thieno[2,3-d][1,3]thiazolyl, thieno[2,3-d]imidazolyl, tetrazolo[1,5-a]pyridinyl, indolyl, indolizinyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, iso benzothiophenyl, indazolyl, benzimidazolyl, 1,3-benzoxazolyl, 1,2-benzisoxazolyl, 2,1-benzisoxazolyl, 1,3-benzothiazolyl, 1,2-benzoisothiazolyl, 2,1-benzoisothiazolyl, benzotriazolyl, 1,2,3-benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl, benzo[d]oxazol-2(3H)-one, 2,3-dihydro-benzofuranyl, thienopyridinyl, purinyl, imidazo[1,2-a]pyridinyl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridin-1(2H)-yl, 6-oxo-pyridazin-1(6H)-yl, 2-oxopyridin-1(2H)-yl, 1,3-benzodioxolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, quinoxalinyl; and wherein at least one carbon atom of said heteroaryl can be oxidized to form at least one CO. [0497] 187. The compound according to any one of statements 1 to 168, 185-186, wherein the group heteroaryl is selected from the group comprising pyrrolyl, furanyl, thiophenyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, oxatriazolyl, thiatriazolyl, pyridinyl, pyrimidyl, pyrazinyl, pyridazinyl, oxazinyl, dioxinyl, thiazinyl, triazinyl, indolyl, indolizinyl, isoindolyl, benzofuranyl, isobenzofuranyl, benzothiophenyl, isobenzothiophenyl, indazolyl, benzimidazolyl, 1,3-benzoxazolyl, 1,2-benzisoxazolyl, 2,1-benzisoxazolyl, 1,3-benzothiazolyl, 1,2-benzoisothiazolyl, 2,1-benzoisothiazolyl, benzotriazolyl, 1,2,3-benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl, benzo[d]oxazol-2(3H)-one, 2,3-dihydro-benzofuranyl, purinyl, 1,3-benzodioxolyl; and wherein at least one carbon atom of said heteroaryl can be oxidized to form at least one CO. [0498] 188. The compound according to any one of statements 1 to 168, 185 to 187, wherein said heteroaryl group is selected from the group consisting of pyridyl, 1,3-benzodioxolyl, benzo[d]oxazol-2(3H)-one, 2,3-dihydro-benzofuranyl, pyrazinyl, pyrazolyl, pyrrolyl, isoxazolyl, thiophenyl imidazolyl, benzimidazolyl, pyrimidinyl, triazolyl and thiazolyl; and wherein at least one carbon atom of said heteroaryl can be oxidized to form at least one CO. [0499] 189. The compound according to any one of statements 1 to 168, and 185 to 188, wherein the group heterocyclyl is selected from the group comprising non-aromatic, fully saturated or partially unsaturated cyclic groups which have at least one heteroatom in at least one carbon atom-containing ring; preferably the group heterocyclyl is selected comprising non-aromatic, fully saturated or partially unsaturated cyclic groups which have at least one heteroatom in at least one carbon atom-containing ring, wherein each ring of the heterocyclyl group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from N, O and/or S, where the N and S heteroatoms may optionally be oxidized and the N heteroatoms may optionally be quaternized; and wherein at least one carbon atom of heterocyclyl can be oxidized to form at least one CO. [0500] 190. The compound according to any one of statements 1 to 168, and 185 to 189, wherein the group heterocyclyl is selected from the group comprising aziridinyl, oxiranyl, thiiranyl, piperidinyl, azetidinyl, oxetanyl, pyrrolidinyl, thietanyl, 2-imidazolinyl, pyrazolidinyl imidazolidinyl, chromanyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, succinimidyl, 3H-indolyl, indolinyl, isoindolinyl, 2H-pyrrolyl, 1-pyrrolinyl, 2-pyrrolinyl, 3-pyrrolinyl, 4H-quinolizinyl, 2-oxopiperazinyl, piperazinyl, homopiperazinyl, 2-pyrazolinyl, 3-pyrazolinyl, tetrahydro-2H-pyranyl, 2H-pyranyl, 4H-pyranyl, 3,4-dihydro-2H-pyranyl, 3-dioxolanyl, 1,4-dioxanyl, 2,5-dioxoimidazolidinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, indolinyl, tetrahydropyranyl, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydroquinolinyl, tetrahydroisoquinolin-1-yl, tetrahydroisoquinolin-2-yl, tetrahydroisoquinolin-3-yl, tetrahydroisoquinolin-4-yl, thiomorpholin-4-yl, thiomorpholin-4-ylsulfoxide, thiomorpholin-4-ylsulfone, 1,3-dioxolanyl, 1,4-oxathianyl, 1,4-dithianyl, 1,3,5-trioxanyl, 1H-pyrrolizinyl, tetrahydro-1,1-dioxothiophenyl, N-formylpiperazinyl, and morpholin-4-yl; and wherein at least one carbon atom of heterocyclyl can be oxidized to form at least one CO.

[0501] According to an embodiment, the present invention provides compounds of formula (I), or (II), and any subgroup thereof such as (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IE), (IIE), (IF), (IIF), (IG), (IIG), (IH), (IIH), (IJ), (IIJ), (IIK), (IIL) wherein,

n is an integer selected from 0, 1, 2 or 3; preferably n is 0, 1 or 2; more preferably n is 0 or 1; more preferably n is 0; [0502] R.sup.1 is selected from the group consisting of C.sub.1-6alkyl, halo, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.1 is selected from the group consisting of C.sub.1-6alkyl, halo, and haloC.sub.1-6alkyl; preferably R.sup.1 is C.sub.1-6alkyl, preferably n is 0 and there is no R.sup.1; [0503] R.sup.2 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, SR.sup.16, halo C.sub.1-6alkyl, haloC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12 aryl can be unsubstituted or substituted with one or more Z.sup.1; preferably R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15 (preferably wherein R.sup.15 is C.sub.1-6alkyl, C.sub.6-12aryl, heteroaryl, or C.sub.3-12cycloalkyl), halo C.sub.1-6alkyl, halo C.sub.1-6alkyloxy, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z; preferably R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, OR.sup.15 (preferably wherein R.sup.15 is C.sub.1-6alkyl, C.sub.6-12aryl, heteroaryl, or C.sub.3-12cycloalkyl), haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; preferably R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-2cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.6-12aryloxy, C.sub.1-6alkyloxy, C.sub.3-12cycloalkyloxy, heterocyclyloxy, heteroaryloxy, haloC.sub.1-6alkyloxy, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.1; [0504] R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12aryl C.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.2; preferably R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, C.sub.1-6alkyloxy, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.2; preferably R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12 cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di C.sub.1-6alkylamino, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.2; [0505] L.sup.1 is a single bond, or is a group of formula (i); preferably L is a single bond or is selected from the group comprising C.sub.1-6alkylene, C.sub.3-6cycloalkylene, or C.sub.1-6alkyleneoxy, wherein each group can be unsubstituted or substituted with one or more substituents each independently selected from halo, or C.sub.1-6alkyl;

##STR00018## [0506] wherein the left side of the group of formula (i) is attached to R.sup.2 and the right side thereof is attached to the oxadiazole ring; and wherein, [0507] m is an integer selected from 0, 1, 2, 3 or 4; preferably m is 0, 1, 2 or 3, preferably m is 0, 1 or 2, preferably m is 0 or 1, preferably m is 1; [0508] p is an integer selected from 0, 1, 2, 3 or 4; preferably p is 0, 1, 2 or 3, preferably p is 0, 1 or 2, preferably p is 0 or 1, preferably p is 0; [0509] L.sup.4 is a single bond, or is selected from the group consisting of O, and NR.sup.8; preferably L.sup.4 is a single bond, or is O; [0510] R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0511] R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0512] or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0513] R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0514] R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0515] or R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0516] R.sup.8 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.8 is selected from the group consisting of hydrogen, and C.sub.1-4alkyl; preferably R.sup.8 is hydrogen; [0517] L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, PO.sub.4, PO.sub.3, and (CR.sup.9R.sup.10).sub.q; wherein, q is an integer selected from 1, 2 or 3; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q; wherein, q is an integer selected from 1, 2 or 3; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q; wherein, q is an integer selected from 1 or 2; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, CH.sub.2, and CH.sub.2CH.sub.2; [0518] R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.9 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.9 is hydrogen; [0519] R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl; preferably R.sup.10 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.10 is hydrogen; [0520] or R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0521] L.sup.3 is a single bond or is selected from the group consisting of (CR.sup.11R.sup.12), O, and NR.sup.13; wherein, r is an integer selected from 1, 2 or 3; preferably, L.sup.3 is a single bond or is selected from the group consisting of O, and (CR.sup.11R.sup.12).sub.r; wherein r is an integer selected from 1, or 2; preferably L.sup.3 is a single bond or is (CR.sup.11R.sup.12).sub.r; wherein, r is an integer selected from 1 or 2; preferably L.sup.3 is a single bond or is selected from CH.sub.2, or CH.sub.2CH.sub.2; [0522] R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16 haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.11 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.11 is hydrogen; [0523] R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, SR.sup.16, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.12 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.12 is hydrogen; [0524] or R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or unsaturated 3-, 4-, 5-, 6- or 7-membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0525] R.sup.13 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.13 is selected from the group consisting of hydrogen, and C.sub.1-4alkyl; preferably R.sup.23 is hydrogen; [0526] wherein at least one of L.sup.2, L.sup.3 is not a single bond; [0527] L.sup.5 is a single bond or CO; [0528] each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; preferably each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl; and wherein said C.sub.1-6alkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; preferably each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; [0529] and wherein at least one carbon atom or heteroatom of C.sub.1-6alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0530] each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, and wherein said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12 arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.2; preferably wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, can be unsubstituted or substituted with one or more Z.sup.2; preferably wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, can be unsubstituted or substituted with one or more Z.sup.2; [0531] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0532] each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0533] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, S, SO or S(O).sub.2; [0534] each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0535] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, N|S, SO or S(O).sub.2; [0536] or wherein R.sup.17 and R.sup.1 together with the nitrogen atom to which they are attached form a 5-, 6-, or 7-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; or preferably wherein [0537] R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-, or 6-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO; or preferably wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO; [0538] each R.sup.19 is independently selected from the group consisting of hydrogen, hydroxyl, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12 arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl; [0539] wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0540] each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0541] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.2-6alkynyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0542] each R.sup.21 is independently selected from C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6 alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene*, and heteroaryleneC.sub.1-6alkylene*; wherein * represents where R.sup.21 is bound to CO; [0543] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene, or heteroaryleneC.sub.1-6alkylene can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; [0544] each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, S(O)R.sup.19, S(O).sub.2R.sup.19, SO.sub.2NR.sup.17R.sup.18, nitro, NR.sup.20C(O)R.sup.19, R.sup.21C(O)NR.sup.11R.sup.18, NR.sup.20S(O).sub.2R.sup.19, and NR.sup.20C(O)NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2, preferably each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, preferably each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, and NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, or 6-membered ring; preferably each Z is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, and cyano; [0545] each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cyclo alkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, S(O)R.sup.19, S(O).sub.2R.sup.19, SO.sub.2NR.sup.17R.sup.18, nitro, NR.sup.20C(O)R.sup.19, R.sup.21C(O)NR.sup.17R.sup.18, NR.sup.20S(O).sub.2R.sup.19, and NR.sup.20C(O)NR.sup.17R.sup.18; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, CS, NO, NS, SO or S(O).sub.2; preferably each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, and C.sub.1-6alkylcarbonyl; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, or 6-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; preferably each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)R.sup.19, and C.sub.1-6alkylcarbonyl; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, or 6-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; preferably each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, halo C.sub.1-6alkyl, C.sub.1-6alkyloxy, halo C.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, and C.sub.1-6alkylcarbonyl. [0546] In an embodiment, for a compound of formula (I) when R.sup.2 is C.sub.6-12aryl; L.sup.3 is a single bond, (CR.sup.11R.sup.12).sub.r. O, or NR.sup.13; then R.sup.3 is not hydrogen, C.sub.1-6alkyl, hydroxyl, or OR.sup.15.

[0547] In an embodiment, for a compound of formula (I) when L.sup.1 is a single bond, R.sup.2 is not hydrogen.

[0548] In an embodiment, said compound is not [0549] 5-(4-((3-methylpyridin-2-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0550] 5-(4-(3-fluorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0551] 3-(4-bromophenyl)-5-(4-(4-fluorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0552] 3-(3,5-dichlorophenyl)-5-(4-(pyridin-2-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0553] 1-(7-methyl-1-(3-(4-(3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)propyl)-1H-indol-3-yl)ethanone; [0554] 5-(4-((2-methoxypyrimidin-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0555] 2-((4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzoic acid; [0556] 5-(4-((2-ethyl-4-methyl-1H-imidazol-5-yl)methyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0557] 3-phenyl-5-(4-((2-phenylthiazol-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; [0558] 5-(4-benzylpiperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; [0559] 5-(4-benzylpiperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; [0560] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0561] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; [0562] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; [0563] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; [0564] 5-(4-benzylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0565] 5-(4-benzylpiperazin-1-yl)-3-(4-methoxyphenyl)-1,2,4-oxadiazole; [0566] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(3-methoxyphenyl)-1,2,4-oxadiazole; [0567] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2,3-dimethoxyphenyl)-1,2,4-oxadiazole; [0568] 3-(4-methoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0569] 3-(3,4-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0570] 3-(2,3-dimethoxyphenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl-1,2,4-oxadiazole; [0571] 3-(2-fluorophenyl)-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0572] 5-(4-benzylpiperazin-1-yl)-3-(2-fluorophenyl)-1,2,4-oxadiazole; [0573] 3-phenyl-5-(4-(2,3,4-trimethoxybenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0574] 5-(4-benzylpiperazin-1-yl)-3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazole; [0575] 5-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; [0576] 5-(4-(benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-methyl-1,2,4-oxadiazole; [0577] 3-(4-bromophenyl)-5-(4-(4-isopropoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0578] 3-(4-bromophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; [0579] 5-(4-(benzo[b][1,4]dioxin-6-ylmethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0580] 5-(4-isobutylpiperazin-1-yl)-3-isopropyl-1,2,4-oxadiazole; [0581] N,N,2,2-tetramethyl-3-[4-(3-phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl]propan-1-amine; [0582] 3-(4-bromophenyl)-5-[4-(2-nitrophenyl)sulfonylpiperazin-1-yl]-1,2,4-oxadiazole; [0583] 5-(4-benzylsulfonylpiperazin-1-yl)-3-cyclopropyl-1,2,4-oxadiazole; [0584] 5-[4-(4-methoxyphenyl)sulfonylpiperazin-1-yl]-3-phenyl-1,2,4-oxadiazole [0585] or a solvate, hydrate, pharmaceutically acceptable salt, or prodrug thereof.

[0586] According to an embodiment, the present invention provides compounds of formula (I), or (II), and any subgroup thereof such as (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IE), (IIE), (IF), (IIF), (IG), (IIG), (IH), (IIH), (IJ), (IIJ), (IIK), (IIL) wherein, [0587] n is 0, 1 or 2, more preferably n is 0 or 1, more preferably n is 0; [0588] R.sup.1 is selected from the group consisting of C.sub.1-6alkyl, halo, and haloC.sub.1-6alkyl; preferably R.sup.1 is C.sub.1-6alkyl; preferably n is 0 and there is no R.sup.1; [0589] R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl, halo, hydroxyl, OR.sup.15, (preferably wherein R.sup.15 is C.sub.1-6alkyl, C.sub.6-12aryl, heteroaryl, or C.sub.3-12cycloalkyl), haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.1; preferably R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6 alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, OR.sup.15, (preferably wherein R.sup.15 is C.sub.1-6alkyl, C.sub.6-12aryl, heteroaryl, or C.sub.3-12cycloalkyl), haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; preferably R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.6-12aryloxy, C.sub.1-6alkyloxy, C.sub.3-12cycloalkyloxy, heterocyclyloxy, heteroaryloxy, haloC.sub.1-6alkyloxy, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.1; [0590] R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, halo, hydroxyl, OR.sup.15, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, NR.sup.17R.sup.18, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6 alkyl, C.sub.3-12 cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, or C.sub.6-12arylC.sub.1-6alkylC.sub.6-12aryl can be unsubstituted or substituted with one or more Z.sup.2; preferably R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di C.sub.1-6alkylamino, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.2; [0591] L.sup.1 is a single bond, or is a group of formula (i); preferably L.sup.1 is a single bond or is a group of formula (i) or is selected from the group comprising C.sub.1-6alkylene, C.sub.3-6cycloalkylene, or C.sub.1-6alkyleneoxy, wherein each group can be unsubstituted or substituted with one or more substituents each independently selected from halo, or C.sub.1-6alkyl;

##STR00019## [0592] wherein the left side of the group of formula (i) is attached to R.sup.2 and the right side thereof is attached to the oxadiazole ring; and wherein, [0593] m is 0, 1, 2 or 3; preferably m is 0, 1 or 2; preferably m is 0 or 1; preferably m is 1; [0594] p is 0, 1, 2 or 3; preferably p is 0, 1 or 2; preferably p is 0 or 1; preferably p is 0; [0595] L.sup.4 is a single bond, or is O; [0596] R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl; preferably R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0597] R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0598] or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.4 and [0599] R.sup.5 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0600] R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0601] R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, hydroxyl, haloC.sub.1-6alkyl, and haloC.sub.1-6alkyloxy; preferably R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0602] or R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0603] R.sup.8 is selected from the group consisting of hydrogen, and C.sub.1-4alkyl; preferably R.sup.8 is hydrogen; [0604] L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q; wherein, q is an integer selected from 1, 2 or 3; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q; wherein, q is an integer selected from 1 or 2; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, CH.sub.2, and CH.sub.2CH.sub.2; [0605] R.sup.9 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.9 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.9 is hydrogen; [0606] R.sup.10 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.10 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.10 is hydrogen; [0607] or R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0608] L.sup.3 is a single bond or is selected from the group consisting of O, and (CR.sup.11R.sup.12).sub.r; wherein, r is an integer selected from 1, or 2; preferably L.sup.3 is a single bond or is (CR.sup.11R.sup.12).sub.r; wherein, r is an integer selected from 1 or 2; preferably L.sup.3 is a single bond; or is selected from CH.sub.2, or CH.sub.2CH.sub.2; [0609] R.sup.11 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.11 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.11 is hydrogen; [0610] R.sup.12 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.12 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.12 is hydrogen; [0611] or R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-, 4-, 5-, 6- or 7-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0612] R.sup.13 is selected from the group consisting of hydrogen, and C.sub.1-4alkyl; preferably R.sup.23 is hydrogen; wherein at least one of L.sup.2, L.sup.3 is not a single bond; [0613] L.sup.5 is a single bond or CO; [0614] each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, and wherein said C.sub.1-6alkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, heteroaryl, and cyanoC.sub.1-6alkyl, can be unsubstituted or substituted with one or more Z.sup.1; preferably each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; [0615] and wherein at least one carbon atom or heteroatom of C.sub.1-6alkyl, C.sub.2-6alkenyl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO; [0616] each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.2; preferably wherein each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.6-12 aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.2; [0617] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, heteroarylC.sub.1-6alkyl, or cyanoC.sub.1-6alkyl can be oxidized to form at least one CO; [0618] each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0619] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; [0620] each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0621] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; [0622] or wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-, or 6-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO; or preferably wherein R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO; [0623] each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0624] wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; [0625] each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0626] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.6-12arylC.sub.1-6alkyl, heterocyclyl, heteroaryl, heterocyclylC.sub.1-6alkyl, and heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; [0627] each R.sup.21 is independently selected from C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene*, and heteroaryleneC.sub.1-6alkylene*; wherein * represents where R.sup.21 is bound to CO; [0628] and wherein at least one carbon atom or heteroatom of said C.sub.1-6alkylene, C.sub.2-6 alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12 aryleneC.sub.1-6alkylene, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene, or heteroaryleneC.sub.1-6alkylene can be oxidized to form at least one CO; [0629] each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, halo C.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, NR.sup.17R.sup.18, and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, 6-, or 7-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO, preferably each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, and NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, or 6-membered ring; preferably each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, halo C.sub.1-6alkyl, halo C.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, and cyano; [0630] each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, heteroarylC.sub.1-6alkyl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)NR.sup.17R.sup.18, C(O)R.sup.19, and C.sub.1-6alkylcarbonyl; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, or 6-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heterocyclylC.sub.1-6alkyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; preferably each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)R.sup.19, and C.sub.1-6alkylcarbonyl; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, or 6-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; preferably each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, and C.sub.1-6alkylcarbonyl.

[0631] According to an embodiment, the present invention provides compounds of formula (I), or (II), and any subgroup thereof such as (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IE), (IIE), (IF), (IIF), (IG), (IIG), (IH), (IIH), (IJ), (IIJ), (IIK), (IIL) wherein, [0632] n is 0 or 1, more preferably n is 0; [0633] R.sup.1 is C.sub.1-6alkyl; preferably n is 0 and there is no R.sup.1; [0634] R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, OR.sup.15, (preferably wherein R.sup.15 is C.sub.1-6alkyl, C.sub.6-12aryl, heteroaryl, or C.sub.3-12cycloalkyl), halo C.sub.1-6alkyl, halo C.sub.1-6alkyloxy, and cyano; and wherein said C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; preferably R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.6-12aryloxy, C.sub.1-6alkyloxy, C.sub.3-12cycloalkyloxy, heterocyclyloxy, heteroaryloxy, haloC.sub.1-6alkyloxy, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.1; [0635] R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6 alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di C.sub.1-6alkylamino, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.2; [0636] L.sup.1 is a single bond or is a group of formula (i) or is selected from the group comprising C.sub.1-6alkylene, C.sub.3-6cycloalkylene, or C.sub.1-6alkyleneoxy, wherein each group can be unsubstituted or substituted with one or more substituents each independently selected from halo, or C.sub.1-6alkyl;

##STR00020## [0637] wherein the left side of the group of formula (i) is attached to R.sup.2 and the right side thereof is attached to the oxadiazole ring; and wherein, [0638] m is 0, 1 or 2, preferably m is 0 or 1, preferably m is 1; [0639] p is 0, 1 or 2, preferably p is 0 or 1, preferably p is 0; [0640] L.sup.4 is a single bond, or is O; [0641] R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0642] R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.5 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0643] or R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.4 and R.sup.5 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0644] R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.6 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0645] R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, halo, and hydroxyl; preferably R.sup.7 is selected from the group consisting of hydrogen, C.sub.1-6alkyl, and halo; [0646] or R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.6 and R.sup.7 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; R.sup.8 is hydrogen; [0647] L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q; wherein q is an integer selected from 1 or 2; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, CH.sub.2, and CH.sub.2CH.sub.2; [0648] R.sup.9 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.9 is hydrogen; [0649] R.sup.10 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.10 is hydrogen; [0650] or R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.9 and R.sup.10 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0651] L.sup.3 is a single bond or is (CR.sup.11R.sup.12).sub.r; wherein r is an integer selected from 1 or 2; preferably L.sup.3 is a single bond, or is selected from CH.sub.2, or CH.sub.2CH.sub.2; [0652] R.sup.11 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.11 is hydrogen; [0653] R.sup.12 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.12 is hydrogen; [0654] or R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-, 4-, or 5-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0655] R.sup.13 is hydrogen; [0656] wherein at least one of L.sup.2, L.sup.3 is not a single bond; [0657] L.sup.5 is a single bond or CO; [0658] each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; [0659] each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.2; [0660] each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0661] each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0662] or R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO; [0663] each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0664] each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0665] each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene*, and heteroaryleneC.sub.1-6alkylene*; wherein * represents where R.sup.21 is bound to CO; [0666] each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, cyano, amino, and NR.sup.17R.sup.18; and wherein two Z.sup.1 together with the atom to which they are attached can form a 5-, or 6-membered ring, preferably each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12 aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, and cyano; [0667] each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6 alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, NR.sup.17R.sup.18, CO.sub.2R.sup.19, C(O)R.sup.19, and C.sub.1-6alkylcarbonyl; and wherein two Z.sup.2 together with the atom to which they are attached can form a 5-, or 6-membered ring; and wherein at least one carbon atom or heteroatom of said ring, C.sub.1-6alkyl, C.sub.3-8cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, or heteroarylC.sub.1-6alkyl can be oxidized to form at least one CO; preferably each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, and C.sub.1-6alkylcarbonyl.

[0668] According to an embodiment, the present invention provides compounds of formula (I) or (II), and any subgroup thereof such as (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IE), (IIE), (IF), (IIF), (IG), (IIG), (IH), (IIH), (IJ), (IIJ), (IIK), (IIL) wherein, [0669] n is 0; [0670] R.sup.2 is selected from the group consisting of C.sub.6-12aryl, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, halo, hydroxyl, C.sub.6-12aryloxy, C.sub.1-6alkyloxy, C.sub.3-12cycloalkyloxy, heterocyclyloxy, heteroaryloxy, haloC.sub.1-6alkyloxy, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.1; [0671] R.sup.3 is selected from the group consisting of C.sub.6-12aryl, hydrogen, C.sub.1-6alkyl, C.sub.3-12cycloalkyl, heterocyclyl, heteroaryl, C.sub.6-12arylC.sub.1-6alkyl, halo, hydroxyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, mono or di C.sub.1-6alkylamino, and cyano; and wherein said group can be unsubstituted or substituted with one or more Z.sup.2; [0672] L.sup.1 is a single bond or is selected from the group comprising C.sub.1-6alkylene, C.sub.3-6cycloalkylene, or C.sub.1-6 alkyleneoxy, wherein each group can be unsubstituted or substituted with one or more substituents each independently selected from halo, or C.sub.1-6alkyl; [0673] L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, and (CR.sup.9R.sup.10).sub.q wherein q is an integer selected from 1 or 2; preferably L.sup.2 is a single bond or is selected from the group consisting of SO.sub.2, CH.sub.2, and CH.sub.2CH.sub.2; [0674] L.sup.3 is a single bond or is (CR.sup.11R.sup.12).sub.r; wherein r is an integer selected from 1 or 2; preferably L.sup.3 is a single bond, or is selected from CH.sub.2, or CH.sub.2CH.sub.2; [0675] R.sup.11 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.11 is hydrogen; [0676] R.sup.12 is selected from the group consisting of hydrogen, and C.sub.1-6alkyl; preferably R.sup.12 is hydrogen; [0677] or R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated or 3-, or 4-carbon membered ring; preferably R.sup.11 and R.sup.12 together with the carbon atom to which they are attached form a saturated 3-carbon membered ring; [0678] wherein at least one of L.sup.2, L.sup.3 is not a single bond; [0679] L.sup.5 is a single bond or CO; [0680] each R.sup.15 is independently selected from the group consisting of C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, C.sub.3-8cyclo alkyl C.sub.1-6alkyl, and hetero aryl; and wherein said C.sub.1-6alkyl, C.sub.3-8cycloalkylC.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.1; [0681] each R.sup.16 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl; and wherein said C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, heterocyclyl, and heteroaryl, can be unsubstituted or substituted with one or more Z.sup.2; [0682] each R.sup.17 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.17 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0683] each R.sup.18 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.18 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0684] or R.sup.17 and R.sup.18 together with the nitrogen atom to which they are attached form a 5-membered heterocyclyl; and wherein at least one carbon atom or heteroatom of said heterocyclyl can be oxidized to form at least one CO; [0685] R.sup.19 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.19 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0686] R.sup.20 is independently selected from the group consisting of hydrogen, C.sub.1-6alkyl, C.sub.6-12aryl, C.sub.3-8cycloalkyl, and heteroaryl; preferably each R.sup.20 is independently selected from the group consisting of hydrogen, and C.sub.1-6alkyl; [0687] each R.sup.21 is independently selected from the group consisting of C.sub.1-6alkylene, C.sub.2-6alkenylene, C.sub.2-6alkynylene, C.sub.6-12arylene, C.sub.3-8cycloalkylene, C.sub.6-12aryleneC.sub.1-6alkylene*, heterocyclylene, heteroarylene, heterocyclyleneC.sub.1-6alkylene*, and heteroaryleneC.sub.1-6alkylene*; wherein * represents where R.sup.21 is bound to CO; [0688] each Z.sup.1 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, C.sub.1-6alkylC.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, and cyano; [0689] each Z.sup.2 is independently selected from the group consisting of halo, hydrogen, C.sub.1-6alkyl, haloC.sub.1-6alkyl, C.sub.1-6alkyloxy, haloC.sub.1-6alkyloxy, C.sub.3-12cycloalkyl, C.sub.6-12aryl, heterocyclyl, heteroaryl, hydroxyl, OR.sup.15, SR.sup.16, C.sub.1-6 alkylthio, cyano, cyanoC.sub.1-6alkyloxy, amino, and C.sub.1-6alkylcarbonyl.

[0690] In some embodiments, said compound is not [0691] 2 [[(2R)-4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-2-methyl-piperazin-1-yl]methyl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine; [0692] 2 [[(2R)-4-(3-rwer-butyl-1,2,4-oxadiazol-5-yl)-2-methyl-piperazin-1-yl]methyl]-7-methoxy-[1,2,4]triazolo[1,5-c]quinazolin-5-amine.

[0693] The present invention also encompasses a pharmaceutical composition comprising one or more pharmaceutically excipients and a therapeutically effective amount of a compound formula (I) or (II), and any subgroup thereof such as (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IE), (IIE), (IF), (IIF), (IG), (IIG), (IH), (IIH), (IJ), (IIJ), (IIK), (IIL).

[0694] The present invention includes all possible stereoisomers compounds of formula (I) or (II) and any subgroup thereof and includes not only racemic compounds but the individual enantiomers as well. When a compound is desired as a single enantiomer, such may be obtained by stereospecific synthesis, by resolution of the final product or any convenient intermediate, or by chiral chromatographic methods as each are known in the art. Resolution of the final product, an intermediate, or a starting material may be effected by any suitable method known in the art. See, for example, Stereochemistry of Organic Compounds by E. L. Eliel, S. H. Wilen, and L. N. Mander (Wiley-Interscience, 1994), incorporated by reference with regard to stereochemistry.

[0695] The compounds of the invention may be in the form of pharmaceutically acceptable salts, as generally described below. Some preferred, but non-limiting examples of suitable pharmaceutically acceptable organic and/or inorganic acids are as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, acetic acid and citric acid, as well as other pharmaceutically acceptable acids known per se (for which reference is made to the prior art referred to below).

[0696] When the compounds of the invention contain an acidic group as well as a basic group the compounds of the invention may also form internal salts, and such compounds are within the scope of the invention. When the compounds of the invention contain a hydrogen-donating heteroatom (e.g. NH), the invention also covers salts and/or isomers formed by transfer of said hydrogen atom to a basic group or atom within the molecule.

[0697] Pharmaceutically acceptable salts of the compounds of formula (I) or (II) and any subgroup thereof include the acid addition and base salts thereof. Suitable acid addition salts are formed from acids which form non-toxic salts. Examples include the acetate, adipate, aspartate, benzoate, besylate, bicarbonate/carbonate, bisulfate/sulfate, borate, camsylate, citrate, cyclamate, edisylate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hibenzate, hydrochloride/chloride, hydrobromide/bromide, hydroiodide/iodide, isethionate, lactate, malate, maleate, malonate, mesylate, methylsulphate, naphthylate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate/hydrogen phosphate/dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, tartrate, tosylate, trifluoroacetate and xinofoate salts. Suitable base salts are formed from bases which form non-toxic salts. Examples include the aluminium, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc salts. Hemisalts of acids and bases may also be formed, for example, hemisulphate and hemicalcium salts. For a review on suitable salts, see Handbook of Pharmaceutical Salts: Properties, Selection, and Use by Stahl and Wermuth (Wiley-VCH, 2002), incorporated herein by reference.

[0698] The compounds of the invention may exist in a continuum of solid states ranging from fully amorphous to fully crystalline. The term amorphous refers to a state in which the material lacks long range order at the molecular level and, depending upon temperature, may exhibit the physical properties of a solid or a liquid. Typically such materials do not give distinctive X-ray diffraction patterns and, while exhibiting the properties of a solid, are more formally described as a liquid. Upon heating, a change from solid to liquid properties occurs which is characterized by a change of state, typically second order (glass transition). The term crystalline refers to a solid phase in which the material has a regular ordered internal structure at the molecular level and gives a distinctive X-ray diffraction pattern with defined peaks. Such materials when heated sufficiently will also exhibit the properties of a liquid, but the change from solid to liquid is characterized by a phase change, typically first order (melting point).

[0699] Pharmaceutically acceptable salts of compounds of formula (I) or (II) may be prepared by one or more of these methods:

(i) by reacting the compound of formula (I) or (II) with the desired acid;
(ii) by reacting the compound of formula (I) or (II) with the desired base;
(iii) by removing an acid- or base-labile protecting group from a suitable precursor of the compound of formula (I) or (II) or by ring-opening a suitable cyclic precursor, for example, a lactone or lactam, using the desired acid; or
(iv) by converting one salt of the compound of formula (I) or (II) to another by reaction with an appropriate acid or by means of a suitable ion exchange column.

[0700] All these reactions are typically carried out in solution. The salt, may precipitate from solution and be collected by filtration or may be recovered by evaporation of the solvent. The degree of ionization in the salt may vary from completely ionized to almost non-ionized.

[0701] The compounds of the invention may also exist in unsolvated and solvated forms. The term solvate is used herein to describe a molecular complex comprising the compound of the invention and one or more pharmaceutically acceptable solvent molecules, for example, ethanol. The term hydrate is employed when said solvent is water.

[0702] A currently accepted classification system for organic hydrates is one that defines isolated site, channel, or metal-ion coordinated hydratessee Polymorphism in Pharmaceutical Solids by K. R. Morris (Ed. H. G. Britain, Marcel Dekker, 1995), incorporated herein by reference. Isolated site hydrates are ones in which the water molecules are isolated from direct contact with each other by intervening organic molecules. In channel hydrates, the water molecules lie in lattice channels where they are next to other water molecules. In metal-ion coordinated hydrates, the water molecules are bonded to the metal ion.

[0703] When the solvent or water is tightly bound, the complex will have a well-defined stoichiometry independent of humidity. When, however, the solvent or water is weakly bound, as in channel solvates and hygroscopic compounds, the water/solvent content will be dependent on humidity and drying conditions. In such cases, non-stoichiometry will be the norm.

[0704] Also included within the scope of the invention are multi-component complexes (other than salts and solvates) wherein the drug and at least one other component are present in stoichiometric or non-stoichiometric amounts. Complexes of this type include clathrates (drug-host inclusion complexes) and co-crystals. The latter are typically defined as crystalline complexes of neutral molecular constituents which are bound together through non-covalent interactions, but could also be a complex of a neutral molecule with a salt. Co-crystals may be prepared by melt crystallization, by recrystallization from solvents, or by physically grinding the components togethersee Chem Commun, 17, 1889-1896, by O. Almarsson and M. J. Zaworotko (2004), incorporated herein by reference. For a general review of multi-component complexes, see J Pharm Sci, 64 (8), 1269-1288, by Haleblian (August 1975), incorporated herein by reference.

[0705] The compounds of the invention may also exist in a mesomorphic state (mesophase or liquid crystal) when subjected to suitable conditions. The mesomorphic state is intermediate between the true crystalline state and the true liquid state (either melt or solution). Mesomorphism arising as the result of a change in temperature is described as thermotropic and that resulting from the addition of a second component, such as water or another solvent, is described as lyotropic. Compounds that have the potential to form lyotropic mesophases are described as amphiphilic and consist of molecules which possess an ionic (such as COO.sup.Na.sup.+, COO.sup.K.sup.+, or SO.sub.3.sup.Na.sup.+) or non-ionic (such as N.sup.N.sup.+(CH.sub.3).sub.3) polar head group. For more information, see Crystals and the Polarizing Microscope by N. H. Hartshorne and A. Stuart, 4.sup.th Edition (Edward Arnold, 1970), incorporated herein by reference.

[0706] All references to compounds of formula (I) or (II) or any subgroups thereof include references to salts, solvates, multi-component complexes and liquid crystals thereof and to solvates, multi-component complexes and liquid crystals of salts thereof.

[0707] The compounds of the invention include compounds of formula (I) or (II) or any subgroups thereof as hereinbefore defined, including all polymorphs and crystal habits thereof, prodrugs and isomers thereof (including optical, geometric and tautomeric isomers) as hereinafter defined and isotopically-labeled compounds of formula (I) or (II).

[0708] In addition, although generally, with respect to the salts of the compounds of the invention, pharmaceutically acceptable salts are preferred, it should be noted that the invention in its broadest sense also included non-pharmaceutically acceptable salts, which may for example be used in the isolation and/or purification of the compounds of the invention. For example, salts formed with optically active acids or bases may be used to form diastereoisomeric salts that can facilitate the separation of optically active isomers of the compounds of formula (I) or (II) above.

[0709] The invention also generally covers all pharmaceutically acceptable prodrugs or pre-drugs of the compounds of formula (I) or (II) or any subgroups thereof for which general reference is made to the prior art cited hereinbelow.

[0710] The term pro-drug as used herein means the pharmacologically acceptable derivatives such as esters, amides and phosphates, such that the resulting in vivo biotransformation product of the derivative is the active drug. The reference by Goodman and Gilman (The Pharmacological Basis of Therapeutics, 8th Ed, McGraw-Hill, Int. Ed. 1992, Biotransformation of Drugs, p 13-15) describing pro-drugs generally is hereby incorporated. Pro-drugs of the compounds of the invention can be prepared by modifying functional groups present in said component in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent component. Typical examples of pro-drugs are described for instance in WO 99/33795, WO 99/33815, WO 99/33793 and WO 99/33792 all incorporated herein by reference. Pro-drugs are characterized by increased bio-availability and are readily metabolized into the active inhibitors in vivo. The term pre-drug, as used herein, means any compound that will be modified to form a drug species, wherein the modification may take place either inside or outside of the body, and either before or after the pre-drug reaches the area of the body where administration of the drug is indicated.

[0711] Where a compound of formula (I) or (II) or any subgroup thereof contains an alkenyl or alkenylene group, geometric cis/trans (or Z/E) isomers are possible. Where structural isomers are interconvertible via a low energy barrier, tautomeric isomerism (tautomerism) can occur. This can take the form of proton tautomerism in compounds of formula (I) containing, for example, an imino, keto, or oxime group, or so-called valence tautomerism in compounds which contain an aromatic moiety. It follows that a single compound may exhibit more than one type of isomerism.

[0712] Included within the scope of the present invention are all stereoisomers, diastereomers, geometric isomers and tautomeric forms of the compounds of formula (I) or (II) or any subgroups thereof, including compounds exhibiting more than one type of isomerism, and mixtures of one or more thereof. Also included are acid addition or base salts wherein the counterion is optically active, for example, d-lactate or /-lysine, or racemic, for example, dl-tartrate or dl-arginine.

[0713] Cis/trans isomers may be separated by conventional techniques well known to those skilled in the art, for example, chromatography and fractional crystallization.

[0714] Conventional techniques for the preparation/isolation of individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high performance liquid chromatography (HPLC).

[0715] The compounds of formula (I) or (II) or any subgroups thereof may be prepared as described in the experimental section below using methods and chemistries with which those skilled in the art shall be familiar.

[0716] Generally, the compounds of the invention are prepared from the intermediates described hereinafter which may be reacted with complementary reactive molecules so as to form the desired compound.

[0717] The present invention also encompasses a compound selected from the group comprising: [0718] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0719] 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0720] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0721] 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0722] 4-(2-(4-(3-Phenyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; [0723] 5-(4-Isopentylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole; [0724] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0725] 5-(4-(4-Chlorobenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0726] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0727] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0728] 5-(4-((4-(Oxazol-5-yl)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0729] 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0730] 3-(p-Tolyl)-5-(4-((4-(trifluoromethoxy)phenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0731] 5-(4-((4-Fluorophenyl) sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0732] 5-(4-((4-Isopropylphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0733] 3-(p-Tolyl)-5-(4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0734] 1-(4-((4-(3-(p-Tolyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenyl)pyrrolidin-2-one; [0735] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole; [0736] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(4-chlorophenyl)-1,2,4-oxadiazole; [0737] 3-(4-Chlorophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole; [0738] 3-(4-Chlorophenyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0739] 3-(4-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0740] 3-(4-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0741] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; [0742] 3-(3-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0743] 3-(3-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0744] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole; [0745] 2-((4-(3-(3-Chlorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile; [0746] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; [0747] 3-(3-Fluorophenyl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0748] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole; [0749] 3-(3-Fluorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0750] 4-(2-(4-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; [0751] 3-(3-Fluorophenyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; [0752] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,4-difluorophenyl)-1,2,4-oxadiazole; [0753] 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0754] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-methoxy-benzenesulfonyl)-piperazine; [0755] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0756] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0757] 1-Benzo[1,3]dioxol-5-ylmethyl-4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-piperazine; [0758] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(2-methyl-benzyl)-piperazine; [0759] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; [0760] 5-((4-(3-Benzyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; [0761] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; [0762] 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0763] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0764] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; [0765] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; [0766] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole; [0767] 1-(4-Methoxy-benzenesulfonyl)-4-[3-((S)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0768] 1-(4-Methoxy-benzenesulfonyl)-4-[3-((R)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0769] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; [0770] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0771] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0772] 1-Benzo[1,3]dioxol-5-ylmethyl-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0773] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; [0774] 5-((4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one; [0775] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; [0776] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(4-chloro-phenyl)-ethyl]-piperazine; [0777] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; [0778] 3-(4-Chlorobenzyl)-5-(4-(2-fluorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0779] 1-(2-Chloro-benzyl)-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0780] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methyl-benzyl)-piperazine; [0781] 4-{4-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-butyronitrile; [0782] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methoxy-ethyl)-piperazine; [0783] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-propyl-piperazine; [0784] 3-(4-Chlorobenzyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; [0785] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4,4,4-trifluoro-butyl)-piperazine; [0786] 3-(4-Chlorobenzyl)-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole; [0787] 4-(2-(4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; [0788] 3-(4-Chlorobenzyl)-5-(4-isopropylpiperazin-1-yl)-1,2,4-oxadiazole; [0789] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; [0790] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0791] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0792] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; [0793] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; [0794] 5-{4-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-3H-benzooxazol-2-one; [0795] 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-dimethylpiperazine-1-sulfonamide; [0796] 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-diethylpiperazine-1-sulfonamide; [0797] 4-((4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)morpholine; [0798] 3-(3-Chlorobenzyl)-5-(4-(pyrrolidin-1-ylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0799] 5-(4-(Azepan-1-ylsulfonyl)piperazin-1-yl)-3-(3-chlorobenzyl)-1,2,4-oxadiazole; [0800] 3-(3-Chlorobenzyl)-5-(4-((4-methoxypiperidin-1-yl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0801] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; [0802] 1-(4-Fluoro-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0803] N-(4-{4-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-phenyl)-acetamide; [0804] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine; [0805] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine; [0806] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-methyl-benzyl)-piperazine; [0807] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; [0808] 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0809] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0810] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-isopropoxy-benzenesulfonyl)-piperazine; [0811] 3-(4-((4-(3-(3-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenoxy)propanenitrile; [0812] 1-(2,3-Dihydro-benzo furan-5-sulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0813] 3-(3-Fluorobenzyl)-5-(4-((4-isopropoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0814] 1-(4-Chloro-benzyl)-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0815] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine; [0816] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; [0817] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0818] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0819] 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0820] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine; [0821] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine; [0822] 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; [0823] 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-piperazine; [0824] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0825] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0826] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0827] 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0828] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; [0829] 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole; [0830] 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; [0831] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; [0832] 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine; [0833] 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0834] 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0835] 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0836] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-(4-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole; [0837] 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0838] 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0839] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0840] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0841] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0842] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0843] 1-(4-Methylsulfanyl-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0844] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0845] 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0846] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0847] 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0848] 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0849] 4-(2-(4-(3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; [0850] 5-(4-Isopentylpiperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole; [0851] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; [0852] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0853] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0854] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0855] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; [0856] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0857] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0858] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0859] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; [0860] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0861] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0862] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0863] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-Piperazine; [0864] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0865] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0866] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(difluoro(4-fluorophenyl)methyl)-1,2,4-oxadiazole; [0867] 3-(Difluoro(4-fluorophenyl)methyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0868] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0869] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine; [0870] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine; [0871] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine; [0872] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0873] 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine; [0874] 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine; [0875] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0876] 3-(Cyclopropylmethyl)-5-(4-((4-methoxyphenyl)sulfanyl)piperazin-1-yl)-1,2,4-oxadiazole; [0877] 3-(Cyclopropylmethyl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0878] 3-(Cyclopropylmethyl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0879] 3-(Cyclopropylmethyl)-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0880] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0881] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0882] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0883] 5-(4-((4-Ethoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0884] 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0885] 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0886] 1-(4-Methoxy-benzenesulfonyl)-4-[3-(2-methyl-pyridin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0887] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-((2-methylpyridin-4-yl)methyl)-1,2,4-oxadiazole; [0888] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0889] 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0890] 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0891] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0892] 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0893] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(3,3,3-tri fluoropropyl)-1,2,4-oxadiazole; [0894] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0895] 2-((4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile [0896] 5-(4-Isopentylpiperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0897] 4-(2-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; [0898] 4-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)butanenitrile; [0899] 5-(4-((6-Methylpyridin-2-yl)methyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole; [0900] 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0901] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-chlorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0902] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole; [0903] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-chlorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0904] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole; [0905] 4-(2-(4-(3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine; [0906] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole; [0907] 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0908] 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0909] 3-(Bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0910] 3-Cyclopropyl-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0911] 3-Cyclopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0912] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2-(2-methylpyridin-4-yl)propan-2-yl)-1,2,4-oxadiazole; [0913] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0914] 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine; [0915] (5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol; [0916] 3-(Methoxymethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0917] 3-((4-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0918] 3-((3-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0919] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(phenoxymethyl)-1,2,4-oxadiazole; [0920] 3-((Cyclopropylmethoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0921] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-((pyridin-3-yloxy)methyl)-1,2,4-oxadiazole; [0922] 4-((5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methoxy)benzonitrile; [0923] 3-((4-Fluorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0924] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-propyl-1,2,4-oxadiazole; [0925] 3-Butyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0926] 3-(Tert-butyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0927] 3-Cyclohexyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0928] 3-Isopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0929] 3-(2-Methoxyethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole; [0930] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; [0931] 5-(7-((4-Methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0932] 5-(7-((4-(Methylthio)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-tri fluoro ethyl)-1,2,4-oxadiazole; [0933] 5-(7-((4-Ethoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0934] 5-(7-((4-(Difluoromethoxy)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole; [0935] (3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methanone; [0936] 3-(4-Fluorobenzyl)-5-(7-(4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole; [0937] 3-(2-Methoxyethyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole;
and a solvate, hydrate, pharmaceutically acceptable salt thereof.

[0938] The present invention also encompasses processes for the preparation of compounds formula (I) or (II) and any subgroup thereof. In the reactions described, it can be necessary to protect reactive functional groups, for example hydroxy, amino, or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups can be used in accordance with standard practice, for example, see T. W. Greene and P. G. M. Wuts in Protective Groups in Organic Chemistry, John Wiley and Sons, 1999. Protected forms of the inventive compounds are included within the scope of the present invention. It will also be clear to the skilled person that compounds of the invention in which one or more functional groups have been protected with suitable functional groups can find use as intermediates in the production and/or synthesis of the compounds of the invention, and as such form a further aspect of the invention.

[0939] The compounds formula (I) or (II), the subgroups thereof and their pharmaceutically acceptable salts can be prepared as described hereunder.

[0940] In the general schemes described below, all substituents are defined as in the general formula (I), (II), (IA), (IIA), (IB), (IIB), (IC), (IIC), (ID), (IID), (IE), (IIE), (IF), (IIF), (IG), (IIG), (IH), (IIH), (IJ), (IIJ), (IIK), (IIL) or any subgroups thereof, unless otherwise mentioned or indicated.

[0941] The present compounds of formula (I) or (II) and their pharmaceutically acceptable salts can be prepared by methods known in the art, for example, by processes described below, which process comprises coupling a compound of formula XII or XIII:

##STR00021##

with a derivative of formula III:

##STR00022##

wherein LG is a leaving group; or by coupling a compound of formula XIV or XVI:

##STR00023##

wherein LG is a leaving group, with a derivative of formula VI:

##STR00024##

to give a compound of formula (I) or (II) or if desired, converting the compounds obtained into pharmaceutically acceptable acid addition salts.

[0942] The preparation of compounds of formula (I) or (II) of the present invention may be carried out in sequential or convergent synthetic routes. In some embodiments, syntheses of the compounds of the invention are shown in the following General Schemes 1 and 2. The skills required for carrying out the reaction and purification of the resulting products are known to those skilled in the art. The substituents and indices used in the following description of the processes have the significance given herein before unless indicated to the contrary.

[0943] In more detail, the compounds of formula (I) or (II) can be manufactured by the methods given below, by the methods given in the examples or by analogous methods. Appropriate reaction conditions for the individual reaction steps are known to a person skilled in the art. The reaction sequence is not limited to the one displayed in General Schemes 1 and 2, however, depending on the starting materials and their respective reactivity the sequence of reaction steps can be freely altered. Starting materials are either commercially available or can be prepared by methods analogous to the methods given below, by methods described in references cited in the description or in the examples, or by methods known in the art.

[0944] The invention includes all stereoisomeric forms, including individual diastereoisomers and enantiomers of the compound of formula (I) or (II) as well as racemic and non-racemic mixtures thereof.

##STR00025##

wherein LG is a leaving group such as CCl.sub.3 or halogen.

[0945] Compounds of formula XII and XIII can be prepared as described in General Scheme 1. The nitrile moiety of intermediate IV is converted into the N-hydroxy amidine intermediate V upon addition of hydroxyl amine. The oxadiazole derivative VI may be formed by reaction with for instance trichloroacetic anhydride in the presence of trichloroacetic acid, whereupon LG is CCl.sub.3. A nucleophilic aromatic substitution of VI with an excess of piperazine at high temperature affords intermediate XII. Alternatively, coupling of VI with commercially available protected piperazine XX (for instance, tert-butyl-piperazine-1-carboxylate), affords VII which after cleavage of the protecting group gives intermediate XII.

[0946] Alternatively, the hydroxy-amidine V can be converted into an oxadiazolone intermediate VIII in a one-step sequence (e.g. with carbonyldiimidazole (CDI)) or in a two steps sequence by reacting it first with ethyl chloroformate followed by thermal cyclisation. Coupling of VIII with commercially available protected piperazine XX (for instance, tert-butyl-piperazine-1-carboxylate) affords VII which after cleavage of the protecting group (e.g. with trifluoroacetic acid (TFA)) gives intermediate XII.

[0947] Coupling of VIII with a commercially available protected 2,7-diazaspiro[3.5]nonane XXI (for instance tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate) affords IX which after cleavage of the protecting group (e.g. with TFA) gives intermediate XIII.

[0948] Compounds of formula XII or XIII can then undergo nucleophilic substitution with compounds of formula III, where the leaving group is typically a halogen to yield compound of formula (I) and (II) respectively.

##STR00026##

[0949] Another possibility to prepare compounds of formula (I) or (II) is described in General Scheme 2. Commercially available protected piperazine XX and 2,7-diazaspiro[3.5]nonane XXII, can be reacted with intermediates of formula III to give protected intermediates of formula X and XI respectively. Deprotection, under standard conditions known to the skilled in the art, leads to derivatives of formula XIV and XV. Nucleophilic aromatic substitution with derivative VI leads to the formation of desired compounds (I) and (II).

[0950] The present invention encompasses compounds according to the invention, as well as the compounds obtained by the methods of the invention. The present invention also encompasses pharmaceutical composition comprising at least one compound of the present invention. The present invention also encompasses pharmaceutical composition comprising at least one compound of the invention and at least one carrier, excipient or diluent acceptable for pharmaceutical purposes.

[0951] In some embodiments, the present invention relates to the use of at least one compound of formula (I) or (II), or any subgroups thereof, in (the preparation of a composition for) the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases, and/or protein misfolding disorders.

[0952] In some embodiments, the present invention relates to a method of prevention and/or of treatment of metabolic disorders and/or neurodegenerative diseases, and/or protein misfolding disorders, comprising administering to a subject in need thereof an effective amount of at least one compound of formula (I) or (II), or any subgroups thereof, or a pharmaceutical composition comprising said at least one compound of formula (I) or (II) or any subgroups thereof.

[0953] In some embodiments, the present invention relates to the use of at least one compound of formula (I) or (II), or any subgroups thereof, in (the preparation of a composition for) the prevention and/or treatment of neurodegenerative disorders and/or protein misfolding disorders, preferably neurodegenerative disorders and/or protein misfolding disorders related to amyloidosis; more preferably neurodegenerative disorders and/or protein misfolding disorders related to synucleinopathies comprising Parkinson's disease, Alzheimer's disease, diffuse Lewy body disease, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy, Huntington's disease, frontotemporal lobar degeneration (FTLD), multiple system atrophy, cystic fibrosis, Creutzfeld-Jacob's disease; yet more preferably for the prevention and/or treatment of Parkinson's disease and/or Alzheimer's disease.

[0954] In some embodiments, the present invention relates to the use of at least one compound of formula (I) or (II), or any subgroups thereof, in (the preparation of a composition for) the prevention and/or treatment of metabolic disorders, preferably metabolic disorders related to amyloidosis, yet more preferably Metabolic disorders such as diabetes mellitus, impaired glucose tolerance, hyperglycemia, hypoglycemia, glyceraldehyde-3-phosphate dehydrogenase deficiency, hyperinsulinism, impaired insulin production, impaired insulin sensitivity, metabolic syndrome, insulin resistance syndrome, obesity, lipidoses, cardiac lipidoses, dyslipidemia, fatty liver, lipodistrophy, cardiovascular diseases, hypertension; yet more preferably diabetes mellitus such as diabetes mellitus type 1 or type 2, more preferably diabetes mellitus type 2.

[0955] The term subject as used herein refers to a mammal. The subject will preferably be a human, but may also be a domestic livestock, laboratory or pet animals.

[0956] In some embodiments, at least one compound of formula (I) or (II) is used (for the preparation of a medicament) for preventing and/or treating a disease selected from the group comprising diabetes mellitus, Parkinson's disease, Alzheimer's disease, diffuse Lewy body disease, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy, Huntington's disease, frontotemporal lobar degeneration (FTLD), multiple system atrophy, cystic fibrosis, Creutzfeld-Jacob's disease, impaired glucose tolerance, hyperglycemia, hypoglycemia, glyceraldehyde-3-phosphate dehydrogenase deficiency, hyperinsulinism, impaired insulin production, impaired insulin sensitivity, metabolic syndrome, insulin resistance syndrome, obesity, lipidoses, cardiac lipidoses, dyslipidemia, fatty liver, lipodistrophy, cardiovascular diseases and hypertension and/or for preventing, treating and/or alleviating complications and/or symptoms associated therewith.

[0957] As used herein, the term effective amount means that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, system, animal, or human that is being sought, for instance, by a researcher or clinician.

[0958] The term therapeutically effective amount means any amount which, as compared to a corresponding subject who has not received such amount, results in improved treatment, healing, prevention, or amelioration of a disease, disorder, or side effect, or a decrease in the rate of advancement of a disease or disorder. The term also includes within its scope amounts effective to enhance normal physiological function.

[0959] For use in therapy, therapeutically effective amounts of a compound of formula (I) or (II), as well as stereoisomers, tautomers, racemics, salts, hydrates or solvates thereof, may be administered as the raw chemical. Additionally, the active ingredient may be presented as a pharmaceutical composition.

[0960] Accordingly, the invention further provides pharmaceutical compositions that include effective amounts of compounds of formula (I) or (II), or stereoisomers, tautomers, racemics, salts, hydrates or solvates thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients. The compounds of formula (I) or (II) or stereoisomers, tautomers, racemics, salts, hydrates or solvates thereof, are as herein described.

[0961] The compounds according to the invention may be administered as the sole active ingredient or together, i.e. in a fixed or free combination, with other therapeutic agents used in clinical practice for the treatment of those diseases listed above.

[0962] The compounds according to the invention and the other pharmaceutical active agent(s) may be administered together or separately and, when administered separately, administration may occur simultaneously or sequentially, in any order. The amounts of the compounds according to the invention and the other pharmaceutically active agent (s) and the relative timings of administration will be selected in order to achieve the desired combined therapeutic effect. The administration in combination of a compound of formula (I) or (II) or a stereoisomer, tautomer, racemic, salt, hydrate or solvate thereof, with other treatment agents may be in combination by administration concomitantly in: (1) a unitary pharmaceutical composition including both compounds; or (2) separate pharmaceutical compositions each including one of the compounds. Alternatively, the combination may be administered separately in a sequential manner wherein one treatment agent is administered first and the other second or vice versa. Such sequential administration may be close in time or remote in time.

[0963] For pharmaceutical use, the compounds of the invention may be used as a free acid or base, and/or in the form of a pharmaceutically acceptable acid-addition and/or base-addition salt (e.g. obtained with non-toxic organic or inorganic acid or base), in the form of a hydrate, solvate and/or complex, and/or in the form or a pro-drug or pre-drug, such as an ester. As used herein and unless otherwise stated, the term solvate includes any combination which may be formed by a compound of this invention with a suitable inorganic solvent (e.g. hydrates) or organic solvent, such as but not limited to alcohols, ketones, esters and the like. Such salts, hydrates, solvates, etc. and the preparation thereof will be clear to the skilled person; reference is for instance made to the salts, hydrates, solvates, etc. described in U.S. Pat. Nos. 6,372,778, 6,369,086, 6,369,087 and 6,372,733.

[0964] The pharmaceutically acceptable salts of the compounds according to the invention, i.e. in the form of water-, oil-soluble, or dispersible products, include the conventional non-toxic salts or the quaternary ammonium salts which are formed, e.g., from inorganic or organic acids or bases. Examples of such acid addition salts include acetate, adipate, alginate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, citrate, camphorate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, ethanesulfonate, fumarate, glucoheptanoate, glycerophosphate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, lactate, maleate, methanesulfonate, 2-naphthalene-sulfonate, nicotinate, oxalate, palmoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, tosylate, and undecanoate. Base salts include ammonium salts, alkali metal salts such as sodium and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases such as dicyclohexylamine salts, N-methyl-D-glucamine, and salts with amino acids such as arginine, lysine, and so forth. In addition, the basic nitrogen-containing groups may be quaternized with such agents as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromides and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl; and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl-bromides and others. Other pharmaceutically acceptable salts include the sulfate salt ethanolate and sulfate salts.

[0965] Generally, for pharmaceutical use, the compounds of the inventions may be formulated as a pharmaceutical preparation comprising at least one compound of the invention and at least one pharmaceutically acceptable carrier, diluent or excipient and/or adjuvant, and optionally one or more further pharmaceutically active compounds.

[0966] By means of non-limiting examples, such a formulation may be in a form suitable for oral administration, for parenteral administration (such as by intravenous, intramuscular or subcutaneous injection or intravenous infusion), for topical administration (including ocular), for administration by inhalation, by a skin patch, by an implant, by a suppository, etc. Such suitable administration forms which may be solid, semi-solid or liquid, depending on the manner of administration as well as methods and carriers, diluents and excipients for use in the preparation thereof, will be clear to the skilled person; reference is again made to for instance U.S. Pat. Nos. 6,372,778, 6,369,086, 6,369,087 and 6,372,733, as well as to the standard handbooks, such as the latest edition of Remington's Pharmaceutical Sciences.

[0967] Some preferred, but non-limiting examples of such preparations include tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols, ointments, cremes, lotions, soft and hard gelatin capsules, suppositories, drops, sterile injectable solutions and sterile packaged powders (which are usually reconstituted prior to use) for administration as a bolus and/or for continuous administration, which may be formulated with carriers, excipients, and diluents that are suitable per se for such formulations, such as lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, polyethylene glycol, cellulose, (sterile) water, methylcellulose, methyl- and propylhydroxybenzoates, talc, magnesium stearate, edible oils, vegetable oils and mineral oils or suitable mixtures thereof. The formulations can optionally contain other pharmaceutically active substances (which may or may not lead to a synergistic effect with the compounds of the invention) and other substances that are commonly used in pharmaceutical formulations, such as lubricating agents, wetting agents, emulsifying and suspending agents, dispersing agents, desintegrants, bulking agents, fillers, preserving agents, sweetening agents, flavoring agents, flow regulators, release agents, etc. . . . The compositions may also be formulated so as to provide rapid, sustained or delayed release of the active compound(s) contained therein, for example using liposomes or hydrophilic polymeric matrices based on natural gels or synthetic polymers. In order to enhance the solubility and/or the stability of the compounds of a pharmaceutical composition according to the invention, it can be advantageous to employ -, - or -cyclodextrins or their derivatives. In addition, co-solvents such as alcohols may improve the solubility and/or the stability of the compounds. In the preparation of aqueous compositions, addition of salts of the compounds of the invention can be more suitable due to their increased water solubility.

[0968] Appropriate cyclodextrins are -, - or -cyclodextrins (CDs) or ethers and mixed ethers thereof wherein one or more of the hydroxyl groups of the anhydroglucose units of the cyclodextrin are substituted with alkyl, particularly methyl, ethyl or isopropyl, e.g. randomly methylated -CD; hydroxyalkyl, particularly hydroxyethyl, hydroxypropyl or hydroxybutyl; carboxyalkyl, particularly carboxymethyl or carboxyethyl; alkylcarbonyl, particularly acetyl; alkoxycarbonylalkyl or carboxyalkoxyalkyl, particularly carboxymethoxypropyl or carboxyethoxypropyl; alkylcarbonyloxyalkyl, particularly 2-acetyloxypropyl. Especially noteworthy as complexants and/or solubilizers are -CD, randomly methylated -CD, 2,6-dimethyl-2-hydroxyethyl--CD, 2-hydroxyethyl--CD, 2-hydroxypropyl--CD and (2-carboxymethoxy)propyl--CD, and in particular 2-hydroxypropyl--CD (2-HP--CD). The term mixed ether denotes cyclodextrin derivatives wherein at least two cyclodextrin hydroxyl groups are etherified with different groups such as, for example, hydroxypropyl and hydroxyethyl. An interesting way of formulating the compounds in combination with a cyclodextrin or a derivative thereof has been described in EP-A-721,331. Although the formulations described therein are with antifungal active ingredients, they are equally interesting for formulating the compounds. Said formulations may also be rendered more palatable by adding pharmaceutically acceptable sweeteners and/or flavors. In particular, the present invention encompasses a pharmaceutical composition comprising an effective amount of a compound according to the invention with a pharmaceutically acceptable cyclodextrin. The present invention also encompasses cyclodextrin complexes consisting of a compound according to the invention and a cyclo dextrin.

[0969] Particular reference is made to the compositions, formulations (and carriers, excipients, diluents, etc. for use therein), routes of administration etc., which are known per se such as those described in U.S. Pat. No. 4,997,834 and EP-A-0 370 498.

[0970] More in particular, the compositions may be formulated in a pharmaceutical formulation comprising a therapeutically effective amount of particles consisting of a solid dispersion of the compounds of the invention and one or more pharmaceutically acceptable water-soluble polymers.

[0971] The term a solid dispersion defines a system in a solid state (as opposed to a liquid or gaseous state) comprising at least two components, wherein one component is dispersed more or less evenly throughout the other component or components. When said dispersion of the components is such that the system is chemically and physically uniform or homogenous throughout or consists of one phase as defined in thermodynamics, such a solid dispersion is referred to as a solid solution. Solid solutions are preferred physical systems because the components therein are usually readily bioavailable to the organisms to which they are administered. The term a solid dispersion also comprises dispersions that are less homogenous throughout than solid solutions. Such dispersions are not chemically and physically uniform throughout or comprise more than one phase.

[0972] The water-soluble polymer is conveniently a polymer that has an apparent viscosity of 1 to 100 mPa.Math.s when dissolved in a 2% aqueous solution at 20 C. solution. Preferred water-soluble polymers are hydroxypropyl methylcelluloses or HPMC. HPMC having a methoxy degree of substitution from about 0.8 to about 2.5 and a hydroxypropyl molar substitution from about 0.05 to about 3.0 are generally water soluble. Methoxy degree of substitution refers to the average number of methyl ether groups present per anhydroglucose unit of the cellulose molecule. Hydroxy-propyl molar substitution refers to the average number of moles of propylene oxide which have reacted with each anhydroglucose unit of the cellulose molecule.

[0973] It may further be convenient to formulate the compounds in the form of nanoparticles which have a surface modifier adsorbed on the surface thereof in an amount sufficient to maintain an effective average particle size of less than 1000 nm. Suitable surface modifiers can preferably be selected from known organic and inorganic pharmaceutical excipients. Such excipients include various polymers, low molecular weight oligomers, natural products, and surfactants. Preferred surface modifiers include nonionic and anionic surfactants.

[0974] Yet another interesting way of formulating the compounds according to the invention involves a pharmaceutical composition whereby the compounds are incorporated in hydrophilic polymers and applying this mixture as a coat film over many small beads, thus yielding a composition with good bio-availability which can conveniently be manufactured and which is suitable for preparing pharmaceutical dosage forms for oral administration. Said beads comprise (a) a central, rounded, or spherical core, (b) a coating film of a hydrophilic polymer and an antiretroviral agent and (c) a seal-coating polymer layer. Materials suitable for use as cores in the beads are manifold, provided that said materials are pharmaceutically acceptable and have appropriate dimensions and firmness. Examples of such materials are polymers, inorganic substances, organic substances, and saccharides, and derivatives thereof.

[0975] The preparations may be prepared in a manner known per se, which usually involves mixing the at least one compound according to the invention with the one or more pharmaceutically acceptable carriers, and, if desired, in combination with other pharmaceutical active compounds, when necessary under aseptic conditions. Reference is again made to U.S. Pat. Nos. 6,372,778, 6,369,086, 6,369,087 and 6,372,733 and the further prior art mentioned above, as well as to the standard handbooks, such as the latest edition of Remington's Pharmaceutical Sciences.

[0976] The pharmaceutical preparations of the invention are preferably in a unit dosage form, and may be suitably packaged, for example in a box, blister, vial, bottle, sachet, ampoule or in any other suitable single-dose or multi-dose holder or container (which may be properly labeled); optionally with one or more leaflets containing product information and/or instructions for use. Generally, such unit dosages will contain between 1 and 1000 mg, and usually between 5 and 500 mg, of the at least one compound of the invention, e.g. about 10, 25, 50, 100, 200, 300 or 400 mg per unit dosage.

[0977] The compounds can be administered by a variety of routes including the oral, ocular, rectal, transdermal, subcutaneous, intravenous, intramuscular or intranasal routes, depending mainly on the specific preparation used and the condition to be treated or prevented, and with oral and intravenous administration usually being preferred. The at least one compound of the invention will generally be administered in an effective amount, by which is meant any amount of a compound of the formula (I) or (II) above that, upon suitable administration, is sufficient to achieve the desired therapeutic or prophylactic effect in the subject to which it is administered. Usually, depending on the condition to be prevented or treated and the route of administration, such an effective amount will usually be between 0.01 to 1000 mg per kilogram, more often between 0.1 and 500 mg, such as between 1 and 250 mg, for example about 5, 10, 20, 50, 100, 150, 200 or 250 mg, per kilogram body weight day of the patient per day, which may be administered as a single daily dose, divided over one or more daily doses, or essentially continuously, e.g. using a drip infusion. The amount(s) to be administered, the route of administration and the further treatment regimen may be determined by the treating clinician, depending on factors such as the age, gender and general condition of the patient and the nature and severity of the disease/symptoms to be treated. Reference is again made to U.S. Pat. Nos. 6,372,778, 6,369,086, 6,369,087 and 6,372,733 and the further prior art mentioned above, as well as to the standard handbooks, such as the latest edition of Remington's Pharmaceutical Sciences.

[0978] In accordance with the method of the present invention, said pharmaceutical composition can be administered separately at different times during the course of therapy or concurrently in divided or single combination forms. The present invention is therefore to be understood as embracing all such regimes of simultaneous or alternating treatment and the term administering is to be interpreted accordingly.

[0979] For an oral administration form, the compositions of the present invention can be mixed with suitable additives, such as excipients, stabilizers or inert diluents, and brought by means of the customary methods into the suitable administration forms, such as tablets, coated tablets, hard capsules, aqueous, alcoholic, or oily solutions. Examples of suitable inert carriers are gum arabic, magnesia, magnesium carbonate, potassium phosphate, lactose, glucose, or starch, in particular, corn starch. In this case, the preparation can be carried out both as dry and as moist granules. Suitable oily excipients or solvents are vegetable or animal oils, such as sunflower oil or cod liver oil. Suitable solvents for aqueous or alcoholic solutions are water, ethanol, sugar solutions, or mixtures thereof. Polyethylene glycols and polypropylene glycols are also useful as further auxiliaries for other administration forms. As immediate release tablets, these compositions may contain microcrystalline cellulose, dicalcium phosphate, starch, magnesium stearate and lactose and/or other excipients, binders, extenders, disintegrants, diluents and lubricants known in the art.

[0980] When administered by nasal aerosol or inhalation, these compositions may be prepared according to techniques well-known in the art of pharmaceutical formulation and may be prepared as solutions in saline, employing benzyl alcohol or other suitable preservatives, absorption promoters to enhance bioavailability, fluorocarbons, and/or other solubilizing or dispersing agents known in the art. Suitable pharmaceutical formulations for administration in the form of aerosols or sprays are, for example, solutions, suspensions or emulsions of the compounds of the invention or their physiologically tolerable salts in a pharmaceutically acceptable solvent, such as ethanol or water, or a mixture of such solvents. If required, the formulation can also additionally contain other pharmaceutical auxiliaries such as surfactants, emulsifiers and stabilizers as well as a propellant.

[0981] For subcutaneous or intravenous administration, the compound according to the invention, if desired with the substances customary therefore such as solubilizers, emulsifiers or further auxiliaries are brought into solution, suspension, or emulsion. The compounds of the invention can also be lyophilized and the lyophilizates obtained used, for example, for the production of injection or infusion preparations. Suitable solvents are, for example, water, physiological saline solution or alcohols, e.g. ethanol, propanol, glycerol, in addition also sugar solutions such as glucose or mannitol solutions, or alternatively mixtures of the various solvents mentioned. The injectable solutions or suspensions may be formulated according to known art, using suitable non-toxic, parenterally-acceptable diluents or solvents, such as mannitol, 1,3-butanediol, water, Ringer's solution or isotonic sodium chloride solution, or suitable dispersing or wetting and suspending agents, such as sterile, bland, fixed oils, including synthetic mono- or diglycerides, and fatty acids, including oleic acid.

[0982] When rectally administered in the form of suppositories, these formulations may be prepared by mixing the compounds according to the invention with a suitable non-irritating excipient, such as cocoa butter, synthetic glyceride esters or polyethylene glycols, which are solid at ordinary temperatures, but liquefy and/or dissolve in the rectal cavity to release the drug.

[0983] The compositions are of value in the veterinary field, which for the purposes herein not only includes the prevention and/or treatment of diseases in animals, but also for economically important animals such as cattle, pigs, sheep, chicken, fish, etc. enhancing the growth and/or weight of the animal and/or the amount and/or the quality of the meat or other products obtained from the animal Thus, in a further aspect, the invention relates to a (pharmaceutical) composition for veterinary use that contains at least one compound of the invention and at least one suitable carrier (i.e. a carrier suitable for veterinary use). The invention also relates to the use of a compound of the invention in the preparation of such a composition.

[0984] The following examples are provided for the purpose of illustrating the present invention and by no means should be interpreted to limit the scope of the present invention.

EXAMPLES

[0985] The synthesis of the compounds of table 1 is described in this experimental part.

TABLE-US-00001 TABLE 1 COM- Example POUND STRUCTURE NAME No Cmpd001 [00027]embedded image 5-(4-(2-(Chlorobenzyl) piperazin-1-yl)-3-phenyl- 1,2,4-oxadiazole 1 Cmpd002 [00028]embedded image 5-(4-(4-Methylbenzyl) piperazin-1-yl)-3-phenyl- 1,2,4-oxadiazole 2 Cmpd003 [00029]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3- phenyl-1,2,4-oxadiazole 3 Cmpd004 [00030]embedded image 5-(4-(2-(2- Methoxypyridin-4- yl)ethyl)piperazin-1- yl)-3-phenyl-1,2,4- oxadiazole 4 Cmpd005 [00031]embedded image 4-(2-(4-(3-Pphenyl- 1,2,4-oxadiazol-5- yl)piperazin-1-yl) ethyl)morpholine 5 Cmpd006 [00032]embedded image 5-(4-Isopentylpiperazin- 1-yl)-3-phenyl-1,2,4- oxadiazole 6 Cmpd007 [00033]embedded image 5-(4-(Benzo[d] [1,3]dioxol-5- ylmethyl)piperazin-1- yl)-3-(p-tolyl)-1,2,4- oxadiazole 7 Cmpd008 [00034]embedded image 5-(4-(4-Chlorobenzyl) piperazin-1-yl)-3-(p- tolyl)-1,2,4-oxadiazole 8 Cmpd009 [00035]embedded image 5-(4-(3- Methoxyphenethyl- piperazin-1-yl)-3- (p-tolyl)-1,2,4- oxadiazole 9 Cmpd010 [00036]embedded image 5-(4-(2-Methylbenzyl) piperazin-1-yl)-3-(p- tolyl)-1,2,4-oxadiazole 10 Cmpd011 [00037]embedded image 5-(4-((4-(Oxazol-5- yl)phenyl)sulfonyl) piperazin-1-yl)-3-(p- tolyl)-1,2,4-oxadiazole 11 Cmpd012 [00038]embedded image 5-(4-((4- (Difluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-3-(p-tolyl)- 1,2,4-oxadiazole 12 Cmpd013 [00039]embedded image 3-(p-Tolyl)-5-(4-((4- (trifluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 13 Cmpd014 [00040]embedded image 5-(4-((4-Fluorophenyl) sulfonyl)piperazin-1-yl)- 3-(p-tolyl)-1,2,4- oxadiazole 14 Cmpd015 [00041]embedded image 5-(4-((4-Isopropylphenyl) sulfonyl)piperazin-1- yl)-3-(p-tolyl)- 1,2,4-oxadiazole 15 Cmpd016 [00042]embedded image 3-(p-Tolyl)-5-(4-((4- (trifluoromethyl)phenyl) sulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 16 Cmpd017 [00043]embedded image 1-(4-((4-(3-(p-Tolyl)- 1,2,4-oxadiazol-5- yl)piperazin-1-yl)sulfonyl) phenyl)pyrrolidin-2- one 17 Cmpd018 [00044]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-(p-tolyl)- 1,2,4-oxadiazole 18 Cmpd019 [00045]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3-(4- chlorophenyl)-1,2,4- oxadiazole 19 Cmpd020 [00046]embedded image 3-(4-Chlorophenyl)-5-(4- phenethylpiperazin-1- yl)-1,2,4-oxadiazole 20 Cmpd021 [00047]embedded image 3-(4-Chlorophenyl)- 5-(4-(3- methoxyphenethyl) piperazin-1-yl)-1,2,4- oxadiazole 21 Cmpd022 [00048]embedded image 3-(4-Chlorophenyl)- 5-(4-(2- methylbenzyl)piperazin- 1-yl)-1,2,4- oxadiazole 22 Cmpd023 [00049]embedded image 3-(4-Chlorophenyl)-5-(4- (2-(2-methoxypyridin- 4-yl)ethyl)piperazin-1- yl)-1,2,4-oxadiazole 23 Cmpd024 [00050]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3-(3- chlorophenyl)-1,2,4- oxadiazole 24 Cmpd025 [00051]embedded image 3-(3-Chlorophenyl)-5-(4- (2-(2-methoxypyridin- 4-yl)ethyl)piperazin-1- yl)-1,2,4-oxadiazole 25 Cmpd026 [00052]embedded image 3-(3-Chlorophenyl)-5- (4-(2- methylbenzyl)piperazin- 1-yl)-1,2,4-oxadiazole 26 Cmpd027 [00053]embedded image 5-(4-(2-Chlorobenzyl) piperazin-1-yl)-3-(3- chlorophenyl)-1,2,4- oxadiazole 27 Cmpd028 [00054]embedded image 2-((4-(3-(3-Chlorophenyl)- 1,2,4-oxadiazol-5- yl)piperazin-1- yl)methyl)benzonitrile 28 Cmpd029 [00055]embedded image 5-(4-(2-Chlorobenzyl) piperazin-1-yl)-3-(3- fluorophenyl)-1,2,4- oxadiazole 29 Cmpd030 [00056]embedded image 3-(3-Fluorophenyl)- 5-(4-(4- methylbenzyl)piperazin-1- yl)-1,2,4- oxadiazole 30 Cmpd031 [00057]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3-(3- fluorophenyl)- 1,2,4-oxadiazole 31 Cmpd032 [00058]embedded image 3-(3-Fluorophenyl)-5-(4- (2-(2-methoxypyridin- 4-yl)ethyl)piperazin-1- yl)-1,2,4-oxadiazole 32 Cmpd033 [00059]embedded image 4-(2-(4-(3-(3- Fluorophenyl)- 1,2,4-oxadiazol-5- yl)piperazin-1-yl)ethyl) morpholine 33 Cmpd034 [00060]embedded image 3-(3-Fluorophenyl)-5- (4-isopentylpiperazin-1- yl)-1,2,4-oxadiazole 34 Cmpd035 [00061]embedded image 5-(4-(2-Chlorobenzyl) piperazin-1-yl)-3-(3,4- difluorophenyl)-1,2,4- oxadiazole 35 Cmpd036 [00062]embedded image 1-[2-(4-Chloro-phenyl)- ethyl]-4-[3-(3,4- difluorophenyl)-[1,2,4] oxadiazol-5-yl]- piperazine 36 Cmpd037 [00063]embedded image 1-(3-Benzyl-[1,2,4] oxadiazol-5-yl)-4-(4- methoxy- benzenesulfonyl)- piperazine 37 Cmpd038 [00064]embedded image 1-(3-Benzyl-[1,2,4] oxadiazole-5-yl)-4- (4-ethoxy- benzenesulfonyl)- piperazine 38 Cmpd039 [00065]embedded image 1-(3-Benzyl-[1,2,4] oxadiazol-5-yl)-4-(4- difluoromethoxy- benzenesulfonyl)- piperazine 39 Cmpd040 [00066]embedded image 1-Benzo[1,3]dioxol-5- ylmethyl-4-(3-benzyl- [1,2,4]oxadiazol-5- yl)-piperazine 40 Cmpd041 [00067]embedded image 1-(3-Benzyl-[1,2,4] oxadiazol-5-yl)-4-(2- methyl-benzyl)- piperazine 41 Cmpd042 [00068]embedded image 1-(3-Benzyl-[1,2,4] oxadiazol-5-yl)-4-[2-(3- methoxy-phenyl)ethyl]- piperazine 42 Cmpd043 [00069]embedded image 5-((4-(3-Benzyl-1,2,4- oxadiazol-5-yl)piperazin- 1-yl)sulfonyl)benzo [d]oxazol-2(3H)-one 43 Cmpd044 [00070]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-(1-phenylpropyl)- 1,2,4-oxadiazole 44 Cmpd045 [00071]embedded image 1-(4-Ethoxy- benzenesulfonyl)- 4-[3-(1-phenyl- propyl)-[1,2,4]oxadiazol- 5-yl]-piperazine 45 Cmpd046 [00072]embedded image 1-(4-Difluoromethoxy- benzenesulfonyl)-4-[3- (1-phenyl-propyl)-[1,2,4] oxadiazol-5-yl]- piperazine 46 Cmpd047 [00073]embedded image 5-(4-(Benzo[d][1,3] dioxol-5- ylmethyl)piperazin-1-yl)- 3-(1-phenylpropyl)- 1,2,4-oxadiazole 47 Cmpd048 [00074]embedded image 5-(4-(2-Methylbenzyl) piperazin-1-yl)-3-(1- phenylpropyl)-1,2,4- oxadiazole 48 Cmpd049 [00075]embedded image 5-(4-(3-Methoxyphenethyl) piperazin-1-yl)-3- (1-phenylpropyl)- 1,2,4-oxadiazole 49 Cmpd050 [00076]embedded image 1-(4-Methoxy- benzenesulfonyl)- 4-[3-((S)-1- phenyl-propyl)-[1,2,4] oxadiazol-5-yl]- piperazine 50 Cmpd051 [00077]embedded image 1-(4-Methoxy- benzenesulfonyl)- 4-[3-((R)-1- phenyl-propyl)-[1,2,4] oxadiazol-5-yl]- piperazine 51 Cmpd052 [00078]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-methoxy- benzenesulfonyl)- piperazine 52 Cmpd053 [00079]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-ethoxy- benzenesulfonyl)- piperazine 53 Cmpd054 [00080]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-difluoromethoxy- benzenesulfonyl)- piperazine 54 Cmpd055 [00081]embedded image 1-Benzo[1,3]dioxol-5- ylmethyl-4-[3-(4-chloro- benzyl)-[1,2,4]oxadiazol- 5-yl]-piperazine 55 Cmpd056 [00082]embedded image 1-[3-(4-Chloro-benzyl- [1,2,4]oxadiazol-5-yl]- 4-[2-(3-methoxy-phenyl)- ethyl]-piperazine 56 Cmpd057 [00083]embedded image 5-((4-(3-(4-Chlorobenzyl)- 1,2,4-oxadiazol-5- yl)piperazin-1-yl)sulfonyl) benzo[d]oxazol- 2(3H)-one 57 Cmpd058 [00084]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(2-methyl-benzyl)- piperazine 58 Cmpd059 [00085]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-[2-(4-chloro-phenyl)- ethyl]-piperazine 59 Cmpd060 [00086]embedded image 1-[3-(4-Chlorobenzyl)- [1,2,4]oxadiazol-5-yl]- 4-[2-(6-methoxy-pyridin- 3-yl)-ethyl]- piperazine 60 Cmpd061 [00087]embedded image 3-(4-Chlorobenzyl)- 5-(4-(2- fluorobenzyl)piperazin- 1-yl)-1,2,4-oxadiazole 61 Cmpd062 [00088]embedded image 1-(2-Chloro-benzyl)-4- [3-(4-chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- piperazine 62 Cmpd063 [00089]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-methyl-benzyl)- piperazine 63 Cmpd064 [00090]embedded image 4-{4-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5- yl]-piperazin-1-yl}- butyronitrile 64 Cmpd065 [00091]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(2-ethoxy-ethyl)- piperazine 65 Cmpd066 [00092]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-propyl-piperazine 66 Cmpd067 [00093]embedded image 3-(4-Chlorobenzyl)-5- (4-isopentylpiperazin-1- yl)-1,2,4-oxadiazole 67 Cmpd068 [00094]embedded image 1-[3-(4-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4,4,4-trifluoro- butyl)-piperazine 68 Cmpd069 [00095]embedded image 3-(4-Chlorobenzyl)-5- (4-((tetrahydro-2H- pyran-4-yl)methyl) piperazin-1-yl)-1,2,4- oxadiazole 69 Cmpd070 [00096]embedded image 4-(2-(4-(3-(4- Chlorobenzyl)- 1,2,4-oxadiazol-5- yl)piperazin-1-yl)ethyl) morpholine 70 Cmpd071 [00097]embedded image 3-(4-Chlorobenzyl)-5- (4-isopropylpiperazin-1- yl)-1,2,4-oxdiazole 71 Cmpd072 [00098]embedded image 1-[3-(3-Chloro-benzyl)- [1,2,4]oxadiaol-5-yl]- 4-(4-methoxy- benzenesulfonyl)- piperazine 72 Cmpd073 [00099]embedded image 1-[3-(3-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-ethoxy- benzenesulfonyl)- piperazine 73 Cmpd074 [00100]embedded image 1-[3-(3-Chloro-benzyl)- [1,2,4]oxadiaozl-5-yl]- 4-(4-difluoromethoxy- benzenesulfonyl)- piperazine 74 Cmpd075 [00101]embedded image 1-[3-(3-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(2-methyl-benzyl)- piperazine 75 Cmpd076 [00102]embedded image 1-[3-(3-Chloro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-[2-(3-methoxy-phenyl)- ethyl]-piperazine 76 Cmpd077 [00103]embedded image 5-{4-[3-(3-Chloro-benzyl)- [1,2,4]oxadiazol-5- yl]-piperazine-1-sulfonyl}- 3H-benzooxazol-2- one 77 Cmpd078 [00104]embedded image 4-(3-(3-Chlorobenzyl)- 1,2,4-oxadiazol-5-yl)- N,N-dimethylpiperazine- 1-sulfonamide 78 Cmpd079 [00105]embedded image 4-(3-(3-Chlorobenzyl)- 1,2,4-oxadiazol-5-yl)- N,N-diethylpiperazine- 1-sulfonamide 79 Cmpd080 [00106]embedded image 4-((4-(3-(3-Chlorobenzyl)- 1,2,4-oxadiazol-5- yl)piperazin-1-yl) sulfonyl)morpholine 80 Cmpd081 [00107]embedded image 3-(3-Chlorobenzyl)-5- (4-(pyrrolidin-1- ylsulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 81 Cmpd082 [00108]embedded image 5-(4-(Azepan-1-ylsulfonyl) piperazin-1-yl)-3-(3- chlorobenzyl)-1,2,4- oxadiazole 82 Cmpd083 [00109]embedded image 3-(3-Chlorobenzyl)-5- (4-((4-methoxypiperidin- 1-yl)sulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 83 Cmpd084 [00110]embedded image 1-[3-(3-Fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-methoxy- benzenesulfonyl)- piperazine 84 Cmpd085 [00111]embedded image 1-(4-Fluoro- benzenesulfonyl)- 4-[3-(3-fluoro- benzyl)-[1,2,4] oxadiazol-5-yl]- piperazine 85 Cmpd086 [00112]embedded image N-(4-{4-[3-(3-Fluoro- benzyl)-[1,2,4]oxadiazol- 5-yl]-piperazine-1- sulfonyl}-phenyl)- acetamide 86 Cmpd087 [00113]embedded image 1-[3-(3-Fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-trifluoromethoxy- benzenesulfonyl)- piperazine 87 Cmpd088 [00114]embedded image 1-[3-(3-Fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(3-trifluoromethyl- benzenesulfonyl)- piperazine 88 Cmpd089 [00115]embedded image 1-[3-(3-Fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(3-methyl-benzyl)- piperazine 89 Cmpd090 [00116]embedded image 1-[3-(3-Fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-[2-(3-methoxy-phenyl)- ethyl]-piperazine 90 Cmpd091 [00117]embedded image 1-(4-Ethoxy- benzenesulfonyl)- 4-[3-(3-fluoro- benzyl)-[1,2,4]oxadiazol- 5-yl]-piperazine 91 Cmpd092 [00118]embedded image 1-(4-Difluoromethoxy- benzenesulfonyl)-4-[3- (3-fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- piperazine 92 Cmpd093 [00119]embedded image 1-[3-(3-Fluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-isopropoxy- benzenesulfonyl)- piperazine 93 Cmpd094 [00120]embedded image 3-(4-((4-(3-(3- Fluorobenzyl)- 1,2,4-oxadiazol-5- yl)piperazin-1- yl)sulfonyl) phenoxy)propanenitrile 94 Cmpd095 [00121]embedded image 1-(2,3-Dihydro-benzofuran- 5-sulfonyl)-4-[3-(3- fluoro-benzyl)-[1,2,4] oxadiazol-5-yl]- piperazine 95 Cmpd096 [00122]embedded image 3-(3-Fluorobenzyl)- 5-(4-((4- isopropoxyphenyl) sulfonyl)piperazin-1-yl)- 1,2,4-oxadiazole 96 Cmpd097 [00123]embedded image 1-(4-Chloro-benzyl)- 4-[3-(3,4-difluoro- benzyl)-[1,2,4] oxadiazol-5-yl]- piperazine 97 Cmpd098 [00124]embedded image 1-[3-(3,4-Difluoro-benzyl)- [1,2,4]oxadiazol-5- yl]-4-[2-(3-methoxy- phenyl)-ethyl]- piperazine 98 Cmpd099 [00125]embedded image 1-[3-(3,4-Difluoro-benzyl)- [1,2,4]oxadiazol-5- yl]-4-(4-methoxy- benzenesulfonyl)- piperazine 99 Cmpd100 [00126]embedded image 1-[3-(3,4-Difluoro-benzyl)- [1,2,4]oxadiazol-5- yl]-4-(4-ethoxy- benzenesulfonyl)- piperazine 100 Cmpd101 [00127]embedded image 1-[3-(3,4-Difluoro-benzyl)- [1,2,4]oxadiazol-5- yl]-4-(4- difluoromethoxy- benzenesulfonyl)- piperazine 101 Cmpd102 [00128]embedded image 1-[2-(4-Chloro-phenyl)- ethyl]-4-[3-(3,4- difluoro-benzyl)- [1,2,4]oxadiazol-5-yl]- piperazine 102 Cmpd103 [00129]embedded image 1-[3-(3,4-Difluoro-benzyl)- [1,2,4]oxadiazol-5- yl]-4-[2-(6-methoxy- pyridin-3-yl)-ethyl]- piperazine 103 Cmpd104 [00130]embedded image 1-[3-(3,4-Difluoro-benzyl)- [1,2,4]oxadiazol-5- yl]-4-(2-methyl-benzyl)- piperazine 104 Cmpd105 [00131]embedded image 1-{3-[1-(4-Fluoro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5- yl}-4-(4-methoxy- benzenesulfonyl)- piperazine 105 Cmpd106 [00132]embedded image 1-(4-Ethoxy- benzenesulfonyl)- 4-{3-[1-(4- fluoro-phenyl)- cyclopropyl]-[1,2,4] oxadiazol-5- yl}-piperazine 106 Cmpd107 [00133]embedded image 3-(1-(4-Fluorophenyl) cyclopropyl)-5-(4-((4- (trifluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 107 Cmpd108 [00134]embedded image 2-(1-(4-Fluorophenyl) cyclopropyl)-5-(4-(2- methylbenzyl)piperazin- 1-yl)-1,2,4-oxadiazole 108 Cmpd109 [00135]embedded image 3-(1-(4-Fluorophenyl) cyclopropyl)-5-(4-(3- methoxyphenethyl) piperazin-1-yl)-1,2,4- oxadiazole 109 Cmpd110 [00136]embedded image 1-{3-[1-(4-Fluoro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl) piperazine 110 Cmpd111 [00137]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3-(1- (4-fluorophenyl) cyclopropyl)- 1,2,4-oxadiazole 111 Cmpd112 [00138]embedded image 5-(4-((2,2-Difluorobenzo [d][1,3]dioxol-5- yl)methyl)piperazin- 1-yl)-3-(1-(4- fluorophenyl) cyclopropyl)- 1,2,4-oxadiazole 112 Cmpd113 [00139]embedded image 1-{3-[1-(4-Fluoro- phenyl)-1-methyl-ethyl]- [1,2,4]oxadiazol-5- yl}-4-(4-methoxy- benzenesulfonyl)- piperazine 113 Cmpd114 [00140]embedded image 1-(4-Difluoromethoxy- benzenesulfonyl)-4-{3- [1-(4-fluoro-phenyl)- 1-methyl-ethyl]- [1,2,4]oxadiazol-5- yl}-piperazine 114 Cmpd115 [00141]embedded image 1-(4-Ethoxy- benzenesulfonyl)- 4-{3-[1-(4- fluoro-phenyl)-1- methyl-ethyl]- [1,2,4]oxadiazol- 5-yl}-piperazine 115 Cmpd116 [00142]embedded image 1-{3-[1-(4-Fluoro- phenyl)-1-methyl-ethyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl)- piperazine 116 Cmpd117 [00143]embedded image 3-(2-(4-Fluorophenyl) propan-2-yl)-5-(4-(2- methylbenzyl)piperazin- 1-yl)-1,2,4-oxadiazole 117 Cmpd118 [00144]embedded image 3-(2-(4-Fluorophenyl) propan-2-yl)-5-(4-(3- methoxyphenethyl) piperaizn-1-yl)-1,2,4- oxadiazole 118 Cmpd119 [00145]embedded image 5-(4-(Benzo[d] [1,3]dioxol-5- ylmethyl)piperazin- 1-yl)-3-(2-(4- fluorophenyl)propan-2- yl)-1,2,4-oxadiazole 119 Cmpd120 [00146]embedded image 1-(4-Methoxy- benzenesulfonyl)-4-[3-(1- phenyl-cyclopropyl)- [1,2,4]oxadiazol-5-yl]- piperazine 120 Cmpd121 [00147]embedded image 1-(4-Ethoxy- benzenesulfonyl)- 4-[3-(1-phenyl- cyclopropyl)-[1,2,4] oxadiazol-5-yl]-piperazine 121 Cmpd122 [00148]embedded image 1-(4-Difluoromethoxy- benzenesulfonyl)-4-[3- (1-phenyl-cyclopropyl)- [1,2,4]oxadiazol-5-yl]- piperazine 122 Cmpd123 [00149]embedded image 5-(4-(2-Methylbenzyl) piperazin-1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 123 Cmpd124 [00150]embedded image 5-(4-(Benzo[d] [1,3]dioxol-5- ylmethyl)piperazin- 1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 124 Cmpd125 [00151]embedded image 5-(4-(3-Methoxyphenethyl) piperazin-1-yl)-3- (1-phenylcyclopropyl)- 1,2,4-oxadiazole 125 Cmpd126 [00152]embedded image 1-(4-Methylsulfanyl- benzenesulfonyl)-4-[3-(1- phenyl-cyclopropyl)- [1,2,4]oxadiazol-5-yl]- piperazine 126 Cmpd127 [00153]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 127 Cmpd128 [00154]embedded image 5-(4-((2,2-Difluorobenzo [d][1,3]dioxol-5- yl)methyl)piperazin- 1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 128 Cmpd129 [00155]embedded image 5-(4-(2-Chlorobenzyl) piperazin-1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 129 Cmpd130 [00156]embedded image 5-(4-(4-Methylbenzyl) piperazin-1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 130 Cmpd131 [00157]embedded image 5-(4-(2-(2- Methoxypyridin-4- yl)ethyl)piperazin- 1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 131 Cmpd132 [00158]embedded image 4-(2-(4-(3-(1- Phenylyclopropyl)-1,2,4- oxadiazol-5-yl)piperazin- 1-yl)ethyl)morpholine 132 Cmpd133 [00159]embedded image 5-(4- Isopentylpiperazin- 1-yl)-3-(1- phenylcyclopropyl)- 1,2,4-oxadiazole 133 Cmpd134 [00160]embedded image 1-{3-[1-(3-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5- yl}-4-(4-methoxy- benzenesulfonyl)- piperazine 134 Cmpd135 [00161]embedded image 1-{3-[1-(3-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5- yl}-4-(4-ethoxy- benzenesulfonyl)- piperazine 135 Cmpd136 [00162]embedded image 1-{3-[1-(3-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-dilfuoromethoxy- benzenesulfonyl)- piperazine 136 Cmpd137 [00163]embedded image 1-{3-[1-(3-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl) piperazine 137 Cmpd138 [00164]embedded image 1-{3-[1-(4-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5- yl}-4-(4-methoxy- benzenesulfonyl)- piperazine 138 Cmpd139 [00165]embedded image 1-{3-[1-(4-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5- yl}-4-(4-ethoxy- benzenesulfonyl)- piperazine 139 Cmpd140 [00166]embedded image 1-{3-[1-(4-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-difluoromethoxy- benzenesulfonyl)- piperazine 140 Cmpd141 [00167]embedded image 1-{3-[1-(4-Chloro- phenyl)-cyclopropyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl)- piperazine 141 Cmpd142 [00168]embedded image 1-{3-[(4-Chloro-phenyl)- difluoro-methyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methoxy- benzenesulfonyl)- piperazine 142 Cmpd143 [00169]embedded image 1-{3-[(4-Chloro-phenyl)- difluoro-methyl]- [1,2,4]oxadiazol-5- yl}-4-(4-ethoxy- benzenesulfonyl)- piperazine 143 Cmpd144 [00170]embedded image 1-{3-[(4-Chloro-phenyl)- difluoro-methyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-difluoromethoxy- benzenesulfonyl)- piperazine 144 Cmpd145 [00171]embedded image 1-{3-[(4-Chloro-phenyl)- difluoro-methyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl)- piperazine 145 Cmpd146 [00172]embedded image 1-{3-[Difluoro-(4- fluoro-phenyl)-methyl]- [1,2,4]oxadiazol-5- yl}-4-(4-methoxy- benzenesulfonyl)- piperazine 146 Cmpd147 [00173]embedded image 1-{3-[Difluoro-(4-fluoro- phenyl)-methyl]- [1,2,4]oxadiazol-5- yl}-4-(4-ethoxy- benzenesulfonyl)- piperazine 147 Cmpd148 [00174]embedded image 1-{3-[Difluoro-(4-fluoro- phenyl)-methyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-difluoromethoxy- benzenesulfonyl)- piperazine 148 Cmpd149 [00175]embedded image 5-(4-Benzo[d] [1,3]dioxol-5- ylmethyl)piperazin- 1-yl)-3-(difluoro(4- fluorophenyl)methyl)- 1,2,4-oxadiazole 149 Cmpd150 [00176]embedded image 3-(Difluoro(4- fluorophenyl) methyl)-5-(4-(3- methoxyphenethyl) piperazin-1-yl)-1,2,4- oxadiazole 150 Cmpd151 [00177]embedded image 1-{3-[Difluoro-(4- fluoro-phenyl)-methyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl)- piperazine 151 Cmpd152 [00178]embedded image 1-{3-[1-(3-Chloro- phenyl)-1-methyl-ethyl]- [1,2,4]oxadiazol-5- yl}-4-(4-methoxy- benzenesulfonyl)- piperazine 152 Cmpd153 [00179]embedded image 1-{3-[1-(3-Chloro-phenyl)- 1-methyl-ethyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-ethoxy- benzenesulfonyl)- piperazine 153 Cmpd154 [00180]embedded image 1-{3-[1-(3-Chloro- phenyl)-1-methyl-ethyl]- [1,2,4]oxadiazol- 5-yl}-4-(4- difluoromethoxy- benzenesulfonyl)- piperazine 154 Cmpd155 [00181]embedded image 1-{3-[1-(3-Chloro- phenyl)-1-methyl-ethyl]- [1,2,4]oxadiazol-5-yl}- 4-(4-methylsulfanyl- benzenesulfonyl)- piperazine 155 Cmpd156 [00182]embedded image 1-[3-(Difluoro- phenyl-methyl)- [1,2,4]oxadiazol-5- yl]-4-(4-methoxy- benzenesulfonyl)- piperazine 156 Cmpd157 [00183]embedded image 1-[3-(Difluoro- phenyl-methyl)- [1,2,4]oxadiazol-5-yl]- 4-(4-methylsulfanyl- benzenesulfonyl)- piperazine 157 Cmpd158 [00184]embedded image 1-(4-Difluoromethoxy- benzenesulfonyl)-4-[3- (difluoro-phenyl-methyl)- [1,2,4]oxadiazol-5- yl]-piperazine 158 Cmpd159 [00185]embedded image 3-(Cyclopropylmethyl)- 5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 159 Cmpd160 [00186]embedded image 3-(Cyclopropylmethyl)- 5-(4-((4- (difluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 160 Cmpd161 [00187]embedded image 3-(Cyclopropylmethyl)- 5-(4-((4- (methylthio)phenyl) sulfonyl)piperazin-1-yl)- 1,2,4-oxadiazole 161 Cmpd162 [00188]embedded image 3-(Cyclopropylmethyl)- 5-(4-((4- ethoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 162 Cmpd163 [00189]embedded image 5-(4-(3- Methoxyphenethyl) piperazin-1-yl)-3- (2,2,2-trifluoroethyl)- 1,2,4-oxadiazole 163 Cmpd164 [00190]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3- (2,2,2-trifluoroethyl)- 1,2,4-oxadiazole 164 Cmpd165 [00191]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-(2,2,2-trifluoroethyl)- 1,2,4-oxadiazole 165 Cmpd166 [00192]embedded image 5-(4-((4-Ethoxyphenyl) sulfonyl)piperazin-1-yl)- 3-(2,2,2-trifluoroethyl)- 1,2,4-oxadiazole 166 Cmpd167 [00193]embedded image 5-(4-((4- (Difluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-3-(2,2,2-trifluoroethyl)- 1,2,4-oxadiazole 167 Cmpd168 [00194]embedded image 5-(4-((4- (Methylthio)phenyl) sulfonyl)piperazin- 1-yl)-3-(2,2,2- trifluoroethyl)- 1,2,4-oxadiazole 168 Cmpd169 [00195]embedded image 1-(4-Methoxy- benzenesulfonyl)-4-[3-(2- methyl-pyridin- 4-ylmethyl)- [1,2,4]oxadiazol-5- yl]-piperazine 169 Cmpd170 [00196]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3-((2- methylpyridin-4-yl) methyl)-1,2,4-oxadiazole 170 Cmpd171 [00197]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-(3,3,3- trifluoropropyl)- 1,2,4-oxadiazole 171 Cmpd172 [00198]embedded image 5-(4-((4-(Methylthio)phenyl) sulfonyl)piperazin- 1-yl)-3-(3,3,3- trifluoropropyl)- 1,2,4-oxadiazole 172 Cmpd173 [00199]embedded image 5-(4-((4- (Difluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-3-(3,3,3-trifluoropropyl)- 1,2,4-oxadiazole 173 Cmpd174 [00200]embedded image 5-(4-(4-Chlorophenethyl) piperazin-1-yl)-3- (3,3,3-trifluoropropyl)- 1,2,4-oxadiazole 174 Cmpd175 [00201]embedded image 5-(4-(2-(2- Methoxypyridin-4- yl)ethyl)piperazin- 1-yl)-3-(3,3,3- trifluoropropyl)- 1,2,4-oxadiazole 175 Cmpd176 [00202]embedded image 5-(4-(2-Methylbenzyl) piperazin-1-yl)-3-(3,3,3- trifluoropropyl)- 1,2,4-oxadiazole 176 Cmpd177 [00203]embedded image 5-(4-(2-Chlorobenzyl) piperazin-1-yl)-3-(3,3,3- trifluoropropyl)- 1,2,4-oxadiazole 177 Cmpd178 [00204]embedded image 2-((4-(3-(3,3,3- Trifluoropropyl)-1,2,4- oxadiazol-5-yl)piperazin-1- yl)methyl)benzonitrile 178 Cmpd179 [00205]embedded image 5-(4-Isopentylpiperazin- 1-yl)-3-(3,3,3- trifluoropropyl)- 1,2,4-oxadiazole 179 Cmpd180 [00206]embedded image 4-(2-(4-(3-(3,3,3- Trifluoropropyl)-1,2,4- oxadiazol-5-yl)piperazin- 1-yl)ethyl)morpholine 180 Cmpd181 [00207]embedded image 4-(4-(3-(3,3,3- Trifluoropropyl)- 1,2,4-oxadiazol- 5-yl)piperazin-1- yl)butanenitrile 181 Cmpd182 [00208]embedded image 5-(4-((6-Methylpyridin- 2-yl)methyl)piperazin- 1-yl)-3- (3,3,3-trifluoropropyl)- 1,2,4-oxadiazole 182 Cmpd183 [00209]embedded image 1-[2-(4-Chloro-phenyl)- ethyl]-4-[3-(4- trifluoromethyl-phenyl)- [1,2,4]oxadiazol-5-yl]- piperazine 183 Cmpd184 [00210]embedded image 3-((1S,4R)-bicyclo[2.2.1] heptan-2-yl)-5-(4-(2- chlorobenzyl)piperazin-1- yl)-1,2,4-oxadiazole 184 Cmpd185 [00211]embedded image 3-((1S,4R)-bicyclo[2.2.1] heptan-2-yl)-5-(4-(4- methylbenzyl)piperazin-1- yl)-1,2,4-oxadiazole 185 Cmpd186 [00212]embedded image 3-((1S,4R)-bicyclo[2.2.1] heptan-2-yl)-5-(4-(4- chlorophenethyl) piperazin-1-yl)-1,2,4- oxadiazole 186 Cmpd187 [00213]embedded image 3-((1S,4R)-bicyclo[2.2.1] heptan-2-yl)-5-(4-(2- (2-methoxypyridin-4- yl)ethyl)piperazin-1-yl)- 1,2,4-oxadiazole 187 Cmpd188 [00214]embedded image 4-(2-(4-(3-((1S,4R)- bicyclo[2.2.1]heptan-2-yl)- 1,2,4-oxadiazol-5- yl)piperazin-1- yl)ethyl)morpholine 188 Cmpd189 [00215]embedded image 3-((1S,4R)-bicyclo [2.2.1]heptan-2-yl)-5-(4- isopentylpiperazin-1- yl)-1,2,4-oxadiazole 189 Cmpd190 [00216]embedded image 3-(Bicyclo[2.2.1] heptan-2-yl)-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 190 Cmpd191 [00217]embedded image 3-(Bicyclo[2.2.1] heptan-2-yl)-5-(4-((4- (methylthio)phenyl) sulfonyl)piperazin-1-yl)- 1,2,4-oxadiazole 191 Cmpd192 [00218]embedded image 3-(Bicyclo[2.2.1] heptan-2-yl)-5-(4-((4- (difluoromethoxy)phenyl) sulfonyl)piperazin-1- yl)-1,2,4-oxadiazole 192 Cmpd193 [00219]embedded image 3-Cyclopropyl-5-(4-((4- ethoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 193 Cmpd194 [00220]embedded image 3-Cyclopropyl-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 194 Cmpd195 [00221]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-(2-(2-methylpyridin- 4-yl)propan-2-yl)- 1,2,4-oxadiazole 195 Cmpd196 [00222]embedded image 1-(4-Difluoromethoxy- benzenesulfonyl)-4-[3- (1-methyl-1-phenyl-ethyl)- [1,2,4]oxadiazol-5- yl]-piperazine 196 Cmpd197 [00223]embedded image 1-(4-Methoxy- benzenesulfonyl)-4-[3-(1- methyl-1-phenyl-ethyl)- [1,2,4]oxadiazol-5-yl]- piperazine 197 Cmpd198 [00224]embedded image (5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-1,2,4-oxadiazol- 3-yl)methanol 198 Cmpd199 [00225]embedded image 3-(Methoxymethyl)- 5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 199 Cmpd200 [00226]embedded image 3-((4-Chlorophenoxy) methyl)-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 200 Cmpd201 [00227]embedded image 3-((3-Chlorophenoxy) methyl)-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 201 Cmpd202 [00228]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-(phenoxymethyl)- 1,2,4-oxadiazole 202 Cmpd203 [00229]embedded image 3-((Cyclopropylmethoxy) methyl)-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 203 Cmpd204 [00230]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-((pyridin-3- yloxy)methyl)-1,2,4- oxadiazole 204 Cmpd205 [00231]embedded image 4-((5-(4-((4- Methoxyphenyl) sulfonyl)piperazin- 1-yl)-1,2,4-oxadiazol-3- yl)methoxy)benzonitrile 205 Cmpd206 [00232]embedded image 3-((4-Fluorophenoxy) methyl)-5-(4-((4- methoxyphenyl)sulofnyl) piperazin-1-yl)-1,2,4- oxadiazole 206 Cmpd207 [00233]embedded image 5-(4-((4-Methoxyphenyl) sulfonyl)piperazin-1- yl)-3-propyl- 1,2,4-oxadiazole 207 Cmpd208 [00234]embedded image 3-Butyl-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 208 Cmpd209 [00235]embedded image 3-(Tert-butyl)-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 209 Cmpd210 [00236]embedded image 3-Cyclohexyl-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 210 Cmpd211 [00237]embedded image 3-Isopropyl-5-(4-((4- methoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 211 Cmpd212 [00238]embedded image 3-(2-Methoxyethyl)- 5-(4-((4- metthoxyphenyl)sulfonyl) piperazin-1-yl)-1,2,4- oxadiazole 212 Cmpd213 [00239]embedded image 3-(1-(4-Fluorophenyl) cyclopropyl)-5-(7-((4- methoxyphenyl) sulfonyl)-2,7- diazaspiro[3.5]nonan-2- yl)-1,2,4-oxadiazole 213 Cmpd214 [00240]embedded image 5-(7-((4-Methoxyphenyl) sulfonyl)-2,7- diazaspiro[3.5]nonan- 2-yl)-3-(2,2,2- trifluoroethyl)- 1,2,4-oxadiazole 214 Cmpd215 [00241]embedded image 5-(7-((4-(Methylthio) phenyl)sulfonyl)-2,7- diazaspiro[3.5]nonan- 2-yl)-3-(2,2,2- trifluoroethyl)-1,2,4- oxadiazole 215 Cmpd216 [00242]embedded image 5-(7-((4-Ethoxyphenyl) sulfonyl)-2,7- diazaspiro[3.5]nonan- 2-yl)-3-(2,2,2- trifluoroethyl)- 1,2,4-oxadiazole 216 Cmpd217 [00243]embedded image 5-(7-((4-(Difluoromethoxy) phenyl)sulfonyl)- 2,7-diazaspiro[3.5] nonan-2-yl)-3-(2,2,2- trifluoroethyl)- 1,2,4-oxadiazole 217 Cmpd218 [00244]embedded image (3-(4-Fluorobenzyl)-1,2,4- oxadiazol-5-yl)(7- ((4-methoxyphenyl) sulfonyl)-2,7- diazaspiro[3,5]nonan- 2-yl)methanone 218 Cmpd219 [00245]embedded image 3-(4-Fluorobenzyl)-5-(7-((4- methoxyphenyl) sulfonyl)-2,7- diazaspiro[3.5]nonan-2- yl)-1,2,4-oxadiazole 219 Cmpd220 [00246]embedded image 3-(2-Methoxyethyl)- 5-(7-((4- methoxyphenyl) sulfonyl)-2,7- diazaspiro[3.5]nonan-2- yl)-1,2,4-oxadiazole 220

Abbreviations

[0986] BOP=(Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate;
CH.sub.2Cl.sub.2=dichloromethane;
DMAP=dimethylaminopyridine;
DMF=dimethylformamide;
EDC1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride;
EE/H=Ethyl acetate/Heptane;
EtOH=ethanol;
EtOAc=ethyl acetate;

Et.SUB.3.Ntriethylamine;

[0987] h=hour;
HPLChigh performance liquid chromatography;
HOBt=1-hydroxy-benzotriazol hydrate;
iPr.sub.2NEt=Ethyl-diisopropyl-amine;
McOH=methanol;
o/n=overnight;
RT=room temperature;
THF=tetrahydrofuran;
TFA=trifluoroacetic acid.

Process for Preparation of Intermediates of Formula IV

Intermediate IV-16; 2-(4-Fluoro-phenyl)-2-methyl-propionitrile

[0988] ##STR00247##

[0989] To a stirred solution of (4-fluoro-phenyl)-acetonitrile (8.0 g, 59.2 mmol) in DMF (80 mL) at 0 C. was added sodium hydride (5.68 g, 50% in oil, 118 mmol). After 40 minutes, methyl iodide (11.1 mL, 178 mmol) was added and the reaction mixture stirred at RT overnight. The reaction mixture was poured on an aqueous saturated solution of NH.sub.4Cl and the product extracted with EtOAc. The combined organic phases were dried on Na.sub.2SO.sub.4, and a column chromatography (silica gel, EtOAc/Heptane=1/9) gave the title product 4.2 g (43%) as a light yellow oil.

Intermediate IV-22; 2-(3-Chloro-phenyl)-2-methyl-propionitrile

[0990] ##STR00248##

[0991] To a stirred solution of (3-chloro-phenyl)-acetonitrile (6.0 g, 39.6 mmol) in DMF (150 mL) at 0 C. was added sodium hydride (3.45 g, 50% in oil, 79.2 mmol). After 40 minutes, methyl iodide (11.1 mL, 178 mmol) was added and the reaction mixture stirred at RT overnight. The reaction mixture was poured on an aqueous saturated solution of NH.sub.4Cl and the product extracted with EtOAc. The combined organic phases were dried on Na.sub.2SO.sub.4, and a column chromatography (silica gel, EtOAc/Heptane=1/9) gave the title product 6.42 g (90%) as a colorless oil.

Intermediate IV-31; 2-Methyl-2-(2-methylpyridin-4-yl)propanenitrile

[0992] ##STR00249##

[0993] In a 100 mL three-necked flask, 2-(2-methylpyridin-4-yl)acetonitrile (950 mg, 7.19 mmol) was combined with DMF (30 ml) to give an orange solution. The solution was then cooled to 0 C. and sodium hydride (690 mg, 14.4 mmol) was added (in 3 portions). The reaction mixture was then stirred for 30 minutes and methyl iodide (3.06 g, 1.35 ml, 21.6 mmol) was added. The reaction mixture was left stirring for 1 h. The reaction mixture was then quenched with sat. ammonium chloride solution and the DMF was evaporated. The crude residue was then poured into sat. ammonium chloride solution and extracted with EtOAc. The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude residue was then purified by column chromatography (silica, EE/H 1:1) to yield 846 mg (5.28 mmol, 73.5%) of 2-methyl-2-(2-methylpyridin-4-yl)propanenitrile. ES-MS m/e: 161.2 (M+H+).

Intermediate IV-32; 2-Methyl-2-phenyl-propionitrile

[0994] ##STR00250##

[0995] To a stirred solution of phenyl-acetonitrile (10 g, 85.4 mmol) in DMF (500 mL) at 0 C. was added sodium hydride (8.18 g, 50% in oil, 187.8 mmol). After 40 minutes, methyl iodide (18.7 mL, 299 mmol) was added and the reaction mixture stirred at RT overnight. The reaction mixture was poured on an aqueous saturated solution of NH.sub.4Cl and the product extracted with EtOAc. The combined organic phases were dried on Na.sub.2SO.sub.4, and a column chromatography (silica gel, EtOAc/Heptane=1/9) gave the title product 6.12 g (49%) as a colorless oil.

Process for Preparation of Intermediates of Formula V

Intermediate V-2; N-hydroxy-4-methylbenzimidamide

[0996] ##STR00251##

[0997] In a 500 ml round bottom flask, hydroxylamine hydrochloride (6.4 g, 92.1 mmol) and sodium bicarbonate (7.74 g, 92.1 mmol) were combined with ethanol (100 ml) and water (20 ml). The suspension was stirred for 15 min. 4-Methylbenzonitrile (9.81 g, 83.7 mmol) was added and the mixture was heated for 5 h at reflux. The reaction was cooled to room temperature. Ethanol was removed by evaporation. The solid residue was suspended in water (100 ml), filtered off and washed with water (330 ml) and heptane (340 ml). The filter cake was dried in vacuo to yield, N-hydroxy-4-methylbenzimidamide (10.8 g, 71.9 mmol, 85.9% yield) as light blue solid. Melting point: 146.8-147.1 C. (Lit: 147 C.)

Intermediate V-7; N-Hydroxy-2-phenyl-acetamidine

[0998] ##STR00252##

[0999] To a solution of the commercially available phenyl-acetonitrile (1.0 g, 8.54 mmol) in ethanol (15 mL) and water (5.0 mL) were added Na.sub.2CO.sub.3 (1.81 g, 17.1 mmol) and hydroxylamine hydrochloride (1.19 g, 17.1 mmol). The reaction mixture was heated to 80 C. for 4 hours, poured into 50 mL water and extracted with EtOAc (150 mL). The organic phase was dried over Na.sub.2SO.sub.4 and concentrated under vacuo. The crude material was purified by flash chromatography (CH.sub.2Cl.sub.2/MeOH 95/5) to afford 1.16 g (90%) of the title compound as a white solid. ES-MS m/e: 151.1 (M+H.sup.+).

[1000] The following acetamidines were prepared according to the same procedure from the commercially available or previously described phenyl-acetonitrile derivatives as shown in Table 2:

TABLE-US-00002 TABLE 2 Phenyl- acetonitrile Reaction derivative Scale time Yield Analysis Structure Name Intermediate 2-phenyl-butyronitrile 5 g o/n 93% ES-MS m/e: 179.1 (M + H.sup.+) [00253]embedded image N-hydroxy-2-phenyl- butyramidine V-8 (4-chloro-phenyl)- acetonitrile 4.5 g 2 h 66% ES-MS m/e: 185.1 (M + H+) [00254]embedded image 2-(4-chloro-phenyl)-N- hydroxy-acetamidine V-9 (3-chloro-phenyl)- acetonitrile 5 g 2 h 75% ES-MS m/e: 185.1 (M + H+) [00255]embedded image 2-(3-chloro-phenyl)-N- hydroxy-acetamidine V-10 (4-fluoro-phenyl)- acetonitrile 2 g 2 h 90% ES-MS m/e: 169.1 (M + H+) [00256]embedded image 2-(4-fluoro-phenyl)-N- hydroxy-acetamidine V-11 (3,4-difluoro-phenyl)- acetonitrile 2 g 3 h 89% ES-MS m/e: 187.1 (M + H+) [00257]embedded image 2-(3,4-Difluoro- phenyl)-N- hydroxy-acetamidine V-13 1-(4-fluoro-phenyl)- cyclopropanecar- bonitrile 3 g o/n 98% ES-MS m/e: 195.2 (M + H+) [00258]embedded image 1-(4-Fluoro-phenyl)-N- hydroxy- cyclopropanecar- boxamidine V-15 IV-16 4.1 g o/n 81% ES-MS m/e: 197.7 (M + H+) [00259]embedded image 2-(4-Fluoro-phenyl)-N- hydroxy- isobutyramidine V-16 1-phenyl- cyclopropanecar- bonitrile 10 g o/n 72% ES-MS m/e: 177.1 (M + H+) [00260]embedded image N-Hydroxy-1-phenyl- cyclopropanecar- boxamidine V-17 1-(3-chloro-phenyl)- cyclopropanecar- bonitrile 2 g 5 h 99% ES-MS m/e: 211.1 (M + H+) [00261]embedded image 1-(3-Chloro-phenyl)-N- hydroxy- cyclopropanecar- boxamidine V-18 1-(4-chloro-phenyl)- cyclopropanecar- bonitrile 3 g 5 h 79% ES-MS m/e: 211.1 (M + H+) [00262]embedded image 1-(4-Chloro-phenyl)-N- hydroxy- cyclopropanecar- boxamidine V-19 (4-chloro-phenyl)- difluoro-acetonitrile 1 g 2 h 80% ES-MS m/e: 221.1 (M + H+ [00263]embedded image 2-(4-Chloro-phenyl)-2,2- difluoro-N-hydroxy- acetamidine V-20 difluoro-(4-fluoro- phenyl)-acetonitrile 1 g 4 h 43% ES-MS m/e: 205.1 (M + H+) [00264]embedded image 2,2-Difluoro-2-(4-fluoro- phenyl)-N-hydroxy- acetamidine V-21 IV-22 1.3 g o/n 47% 213.1 (M + H+) [00265]embedded image 2-(3-Chloro-phenyl)-N- hydroxy-isobutyramidine V-22 difluoro-phenyl- acetonitrile 2 g 2 h 82% ES-MS m/e: 187.1 (M + H+). [00266]embedded image 2,2-Difluoro-N- hydroxy-2- phenyl-acetamidine V-23 (2-methyl-pyridin-4- yl)-acetonitrile 1.07 g o/n 86% ES-MS m/e: 166.2 (M + H+) [00267]embedded image N-Hydroxy-2-(2-methyl- pyridin-4-yl)- acetamidine V-26 4,4,4- trifluorobutanenitrile 2 g o/n 71% ES-MS m/e: 157.1 (M + H+) [00268]embedded image 4,4,4-trifluoro-N- hydroxybutanimidamide V-27 (1S,2S,4R)- bicyclo[2.2.1]heptane- 2-carbonitrile 3.5 g 5 h 34% ES-MS m/e: 155.2 (M + H+) [00269]embedded image (1S,4R)-N- hydroxybi- cyclo[2.2.1]heptane- 2-carboximidamide V-29 IV-31 836 mg o/n 60% [00270]embedded image N-hydroxy-2- methyl-2-(2- methylpyridin-4- yl)propanimidamide V-31 IV-32 1.62 g o/n 41% ES-MS m/e: 179.1 (M + H+) [00271]embedded image N-Hydroxy-2-phenyl- isobutyramidine V-32 ethyl carbonocyanidate 1.6 g o/n 89% [00272]embedded image ethyl 2-amino-2- (hydroxyimino)acetate V-33 3- methoxypropanenitrile 2 g o/n 10% [00273]embedded image N-hydroxy-3- methoxypro- panimidamide V-39

Intermediate V-24; 2-cyclopropyl-N-hydroxyacetimidamide

[1001] ##STR00274##

[1002] In a 250 mL round-bottomed flask, cyclopropylacctonitrile (5 g, 61.6 mmol), sodium carbonate (13.1 g, 123 mmol) and hydroxylamine hydrochloride (8.57 g, 123 mmol) were combined with ethanol (120 ml) and water (40.0 ml). The reaction mixture was heated to 80 C. and stirred overnight. The ethanol was evaporated. Then, the thick white mixture was poured into EtOAc and extracted with water. The organic phase dried over Na.sub.2SO.sub.4 and evaporated to give 7.04 g of crude 2-cyclopropyl-N-hydroxyacetimidamide which was used in the next step without further purification.

[1003] The following acetamidines were prepared according to the same procedure from the commercially available phenyl-acetonitrile derivatives as shown in Table 3:

TABLE-US-00003 TABLE 3 Phenyl- acetonitrile Reaction derivative Scale time Yield Structure Name Intermediate 3,3,3- trifluoropropionitrile 4.33 g o/n 13% [00275]embedded image 3,3,3-trifluoro-N- hydroxypropanimidamide V-25 butyronitrile 2 g o/n 30% [00276]embedded image N- hydroxybutyrimidamide V-34 pentanenitrile 2 g o/n 60% [00277]embedded image N- hydroxypentanimidamide V-35

Process for Preparation Intermediates of Formula VI

Intermediate VI-7; 3-Benzyl-5-trichloromethyl-[1,2,4]oxadiazole

[1004] To N-hydroxy-2-phenyl-acetamidine (1.14 g, 7.59 mmol) were added trichloroacetic anhydride (2.91 mL, 15.9 mmol) and trichloroacetic acid (4.96 g). The reaction mixture was heated to 115 C. for 20 minutes, cooled down to RT, diluted with EtOAc (100 mL), washed several times with water, and then with an aqueous solution of NaHCO.sub.3. The organic phase was dried over Na.sub.2SO.sub.4, concentrated under vacuo and the resulting crude material was purified by chromatography (silica gel, EtOAc/Heptane: 1/6) to give 1.66 g (79%) as a light yellow oil.

[1005] The following 5-trichloromethyl-[1,2,4]oxadiazole intermediates were prepared according to the same procedure from the commercially available or previously described amidine derivatives as shown in Table 4:

TABLE-US-00004 TABLE 4 Phenyl- acetonitrile Reaction derivatives Scale time Yield Analysis Structure Name Intermediate V-8 5.40 g 30 min 95% ES-MS m/e: 305.0/ 306.9 (M + H+) [00278]embedded image 3-(1-phenylpropyl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-8 V-9 2.0 g 20 min 73% [00279]embedded image 3-(4-chlorobenzyl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-9 V-10 4.56 g 30 min 77% [00280]embedded image 3-(3-chlorobenzyl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-10 V-11 2.48 g 30 min 73% ES-MS m/e: 294 (M + H+) [00281]embedded image 3-(4-fluorobenzyl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-11 V-13 492 mg 30 min 38% Light yellow oil [00282]embedded image 3-(3,4-Difluoro-benzyl)-5- trichloromethyl- [1,2,4]oxadiazole VI-13 V-16 2.0 g 40 min 88% Light yellow oil [00283]embedded image 3-[1-(4-Fluoro-phenyl)-1- methyl-ethyl]-5- trichloromethyl- [1,2,4]oxadiazole VI-16 V-17 3.50 g 1 h Waxy oil [00284]embedded image 3-(1-Phenyl-cyclopropyl)- 5-trichloromethyl- [1,2,4]oxadiazole VI-17 V-18 2.18 g 1 h 72% Waxy oil [00285]embedded image 3-[1-(3-Chloro-phenyl)- cyclopropyl]-5- trichloromethyl- [1,2,4]oxadiazole VI-18 V-19 1.4 g 90 min 77% Waxy oil [00286]embedded image 3-[1-(4-Chloro-phenyl)- cyclopropyl]-5- trichloromethyl- [1,2,4]oxadiazole VI-19 V-20 940 mg 20 min 80% White solid [00287]embedded image 3-[(4-Chloro-phenyl)- difluoro-methyl]-5- trichloromethyl- [1,2,4]oxadiazole VI-20 V-21 520 mg 30 min 69% Colorless oil [00288]embedded image 3-[Difluoro-(4-fluoro- phenyl)-methyl]-5- trichloromethyl- [1,2,4]oxadiazole VI-21 V-22 715 mg 30 min 82% White solid [00289]embedded image 3-[1-(3-Chloro-phenyl)-1- methyl-ethyl]-5- trichloromethyl- [1,2,4]oxadiazole VI-22 V-23 1.90 g 40 min 92% White solid [00290]embedded image 3-(Difluoro-phenyl- methyl)-5- trichloromethyl- [1,2,4]oxadiazole VI-23 V-26 1.10 g 70 min 11% Waxy oil [00291]embedded image 2-Methyl-4-(5- trichloromethyl- [1,2,4]oxadiazol-3- ylmethyl)-pyridine VI-26 V-27 1.75 g 60 min 90% ES-MS m/e: 157.1 (M + H+) [00292]embedded image 5-(trichloromethyl)-3- (3,3,3-trifluoropropyl)- 1,2,4-oxadiazole VI-27 V-29 1.4 g 20 min 74% Colorless oil [00293]embedded image 3-((1S,4R)- bicyclo[2.2.1]heptan-2- yl)-5-(trichloromethyl)- 1,2,4-oxadiazole VI-29 N- hydroxycyclo- propane carboximidamide 900 mg 30 min 68% [00294]embedded image 3-cyclopropyl-5- (trichloromethyl)-1,2,4- oxadiazole VI-30 V-31 200 mg 15 min 87% Colorless oil [00295]embedded image 3-(2-(2-methylpyridin-4- yl)propan-2-yl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-31 V-32 820 mg 30 min 82% Colorless oil [00296]embedded image 3-(1-Methyl-1-phenyl- ethyl)-5-trichloromethyl- [1,2,4]oxadiazole VI-32 V-33 2.5 g 15 min 92% Yellow oil [00297]embedded image ethyl 5-(trichloromethyl)- 1,2,4-oxadiazole-3- carboxylate VI-33 V-34 800 mg 45 min 49% [00298]embedded image 3-propyl-5- (trichloromethyl)-1,2,4- oxadiazole VI-34 V-35 2.3 g 30 min 89% [00299]embedded image 3-butyl-5- (trichloromethyl)-1,2,4- oxadiazole VI-35 N- hydroxypivali- midamide 500 mg 60 min 54% [00300]embedded image 3-(tert-butyl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-36 N- hydroxycyclo- hexane carboximidamide 500 mg 60 min 51% [00301]embedded image 3-cyclohexyl-5- (trichloromethyl)-1,2,4- oxadiazole VI-37 N-hydroxyiso- butyrimidamide 300 mg 30 min 41% [00302]embedded image 3-isopropyl-5- (trichloromethyl)-1,2,4- oxadiazole VI-38 V-39 250 mg 30 min 60% [00303]embedded image 3-(2-methoxyethyl)-5- (trichloromethyl)-1,2,4- oxadiazole VI-39

Intermediate VI-27; 3-(Cyclopropylmethyl)-5-(trichloromethyl)-1,2,4-oxadiazole

[1006] ##STR00304##

[1007] A suspension of 2-cyclopropyl-N-hydroxy-acetamidine V-24 (625 mg, 5.48 mmol), trichloroacetic acid (3.58 g, 21.9 mmol) and trichloroacetic anhydride (3.55 g, 2.1 ml, 11.5 mmol) under argon atmosphere was heated to 110 C. for 40 minutes. The resulting brown solution was diluted with water (200 ml) and neutralized with a saturated solution of NaHCO.sub.3 and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na.sub.2SO.sub.4 and evaporated to give 1.36 g of a dark brown oil which was used in the next step without further purification.

[1008] The following 5-trichloromethyl-[1,2,4]oxadiazole intermediates were prepared according to the same procedure from the commercially available or previously described amidine derivatives as shown in Table 5:

TABLE-US-00005 TABLE 5 Phenyl- acetonitrile Reaction derivative Scale time Yield Structure Name Intermediate V-25 718 mg 60 min 96% [00305]embedded image 5- (trichloromethyl)- 3-(2,2,2- trifluoroethyl)- 1,2,4-oxadiazole VI-25

Process for Preparation Intermediates of Formula VIII

Intermediate VIII-1; 3-Phenyl-4H-[1,2,4]oxadiazol-5-one

[1009] ##STR00306##

[1010] To a solution of N-hydroxy-benzamidine (5.0 g, 36.7 mmol) in acetonitrile (150 mL) was added 1,1-carbonyldiimidazole (6.55 g, 40.5 mmol). The reaction mixture was heated to reflux for five hours, cooled down to RT, concentrated under vacuo and purified by column chromatography (EtOAc/Heptane 4/1) to give 3.8 g (64%) of the title product as a white solid.

[1011] The following oxadiazol-5-one intermediates were prepared according to the same procedure from the commercially available or previously described amidine derivatives as shown in Table 6:

TABLE-US-00006 TABLE 6 Amidine Reaction derivative Scale time Yield Analysis Structure Name Intermediate V-2 5 g 15 h 56.6% ES-MS m/e: 175.0 (M H.sup.+) [00307]embedded image 3-p-Tolyl-4H- [1,2,4]oxadiazol-5- one VIII-2 4-chloro-N- hydroxy- benzamidine 5 g 5 h 46% ES-MS m/e: 195.0 (M H+) [00308]embedded image 3-(4-Chloro-phenyl)- 4H-[1,2,4]oxadiazol- 5-one VIII-3 3-chloro-N- hydroxy- benzamidine 4 g 6 h 32% ES-MS m/e: 195.1 (M H+) [00309]embedded image 3-(3-Chloro-phenyl)- 4H-[1,2,4]oxadiazol- 5-one VIII-4 3-fluoro-N- hydroxy- benzamidine 4 g 5 h 38% ES-MS m/e: 179.0 (M H+) [00310]embedded image 3-(3-Fluoro-phenyl)- 4H-[1,2,4]oxadiazol- 5-one VIII-5 3,4-difluoro-N- hydroxy- benzamidine 5 g 5 h 25% ES-MS m/e: 197.1 (M H+) [00311]embedded image 3-(3,4-Difluoro- phenyl)-4H- [1,2,4]oxadiazol-5- one VIII-6 N-hydroxy-4- trifluoromethyl- benzamidine l g 5 h 54% ES-MS m/e: 229.2 (M H+) [00312]embedded image 3-(4- Trifluoromethyl- phenyl)-4H- [1,2,4]oxadiazol-5- one VIII-28

Intermediate VIII-15; 3-[1-(4-Fluoro-phenyl)-cyclopropyl]-4H-[1,2,4]oxadiazol-5-one

[1012] ##STR00313##

[1013] 1-(4-Fluoro-phenyl)-N-hydroxy-cyclopropanecarboxamidine (1.66 g, 8.55 mmol) and Et.sub.3N (1.79 mL, 12.8 mmol) were combined with CH.sub.2Cl.sub.2 (16 mL) to give a colorless solution. Ethyl chloroformate (0.83 mL, 8.72 mmol) was added dropwise and stirred for one hour. The reaction was poured on CH.sub.2Cl.sub.2 (100 mL) and washed with water. The organic layer was dried over Na.sub.2SO.sub.4, concentrated under vacuo. The crude residue was dissolved in toluene (30 mL) and heated to 125 C. overnight. Concentration under vacuo and column flash chromatography afforded 1.4 g (74%) of the title product as a white solid.

Process for Preparation Intermediates of Formula VII

Intermediate VII-1; 4-(3-Phenyl-[1,2,4]oxadiazol-5-yl)-piperazine-1-carboxylic acid tert-butyl ester

[1014] ##STR00314##

[1015] To a solution of 3-phenyl-4H-[1,2,4]oxadiazol-5-one VIII-1 (3.60 g, 22.2 mmol) in DMF (125 mL) was added iPr.sub.2NEt (19.4 mL, 111 mmol), piperazine-1-carboxylic acid tert-butyl ester (8.27 g, 44.4 mmol) and BOP (10.8 g, 24.4 mmol). The reaction mixture was stirred at reflux for 24 hours. The volatiles were removed under vacuo, and the residue taken up in EtOAC and washed with a saturated aqueous solution of NaHCO.sub.3. The organic phase was dried over Na.sub.2SO.sub.4, concentrated under vacuo, and a column chromatography (EtOAc/Heptane 1/4) gave 2.1 g (28%) of the title product as a white powder.

[1016] The following oxadiazol-5-one intermediates were prepared according to the same procedure from the commercially available or previously described oxazol-5-one derivatives as shown in Table 7:

TABLE-US-00007 TABLE 7 Amidine Reaction Inter- derivative Scale time Yield Analysis Structure Name mediate VIII-3 1.7 g 24 h 27% ES-MS m/e: 365.1 (M + H+). [00315]embedded image 4-[3-(4-Chloro- phenyl)- [1,2,4]oxadiazol- 5-yl]-piperazine-1- carboxylic acid tert-butyl ester VII-3 VIII-4 1.5 g 24 h 26% White powder [00316]embedded image 4-[3-(3-Chloro- phenyl)- [1,2,4]oxadiazol- 5-yl]-piperazine-1- carboxylic acid tert-butyl ester VII-4 VIII-5 1.6 g 20 h 23% White powder [00317]embedded image tert-butyl 4-(3-(3- fluorophenyl)-1,2,4- oxadiazol-5- yl)piperazine-1- carboxylate VII-5 VIII-6 1.43 g 24 h 12% White powder [00318]embedded image 4-[3-(3,4-Difluoro- phenyl)- [1,2,4]oxadiazol- 5-yl]-piperazine-1- carboxylic acid tert-butyl ester VII-6 3-(3- fluoro- benzyl)- 4H- [1,2,4]oxa- diazol-5- one 1.40 g o/n 28% ES-MS m/e: 363.3 (M + H.sup.+) [00319]embedded image 4-[3-(3-Fluoro- benzyl)- [1,2,4]oxadiazol- 5-yl]-piperazine-1- carboxylic acid tert-butyl ester VII-12 VIII-15 1.4 g o/n 36% White powder [00320]embedded image 4-{3-[1-(4-Fluoro- phenyl)- cyclopropyl]- [1,2,4]oxadiazol- 5-yl}-piperazine-1- carboxylic acid tert-butyl ester VII-15 VIII-28 600 mg 24 h 9% White powder [00321]embedded image 4-[3-(4- Trifluoromethyl- phenyl)- [1,2,4]oxadiazol- 5-yl]-piperazine-1- carboxylic acid tert-butyl ester VII-28

Process for Preparation Intermediates of Formula XII

Intermediate XII-2; 1-(3-p-Tolyl-[1,2,4]oxadiazol-5-yl)-piperazine

[1017] ##STR00322##

[1018] 3-p-Tolyl-4H-[1,2,4]oxadiazol-5-one VIII-2 (3.35 g, 19.0 mmol) was suspended in POCl.sub.3 (6.2 mL, 66.6 mmol) and pyridine (0.769 mL, 9.51 mmol) was added dropwise. Upon heating to reflux, the reaction mixture turned into a brown solution. After 22 hours, it was cooled to RT and carefully poured onto ice, and the product extracted with EtOAc (2 times 50 mL). The organic phase was dried on Na.sub.2SO.sub.4, concentrated under vacuo, and a column chromatography (EtOAc/Heptane: 1:9 to 3:7) gave 2.77 g (75%) of 5-chloro-3-p-tolyl-[1,2,4]oxadiazole as a light yellow oil.

[1019] To a solution of 5-chloro-3-p-tolyl-[1,2,4]oxadiazole (0.95 g, 4.88 mmol) in EtOH (10 mL), was added iPr.sub.2NEt (2.56 mL, 14.6 mmol) and piperazine (0.681 g, 7.91 mmol). The resulting mixture was heated to reflux for 30 minutes, cooled to RT, concentrated under vacuo. A column chromatography (EtOAc/heptane 3/7 to EtOAc/MeOH 9/1) gave 360 mg (30%) of the title product as a light yellow viscous oil. ES-MS m/e: 245.4 (MH.sup.+).

Intermediate XII-3; 1-[3-(4-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1020] ##STR00323##

[1021] To a solution of 4-[3-(4-chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester VII-3 (0.85 g, 2.33 mmol) in CH.sub.2Cl.sub.2 (18 mL) was added TFA (4 mL). After stirring 2 hours at RT, the reaction mixture was diluted with CH.sub.2Cl.sub.2 (100 mL) and a saturated aqueous solution of NaHCO.sub.3 was added until pH=8. The organic phase was dried over Na.sub.2SO.sub.4, concentrated under vacuo, and a column chromatography (CH.sub.2Cl.sub.2/MeOH 9/1) gave 0.56 g (90%) of the title product as a white solid. ES-MS m/e: 265.1 (MH.sup.+).

[1022] The following intermediates of formula XII were prepared according to the same procedure from intermediates VII previously described as shown in Table 8:

TABLE-US-00008 TABLE 8 Reaction Intermediate Scale time Yield Analysis Structure Name Intermediate VII-1 2.1 g 2 h 52% ES-MS m/e: 231.2 (M H.sup.+) [00324]embedded image 1-(3-Phenyl- [1,2,4]oxadiazol-5- yl)-piperazine XII-1 VII-4 724 mg 2 h 58% ES-MS m/e: 265.1 (M H.sup.+) [00325]embedded image 1-[3-(3-Chloro- phenyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-4 VII-5 690 mg 2 h 37% ES-MS m/e: 249.1 (M H.sup.+) [00326]embedded image 1-[3-(3-Fluoro- phenyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-5 VII-6 323 mg 2 h 20% ES-MS m/e: 267.1 (M H.sup.+) [00327]embedded image 1-[3-(3,4-Difluoro- phenyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-6 VII-12 750 mg 1 h 97% ES-MS m/e: 263.5 (M + H.sup.+) [00328]embedded image 1-[3-(3-Fluoro- benzyl)- [1,2,4]oxadiazo1-5- yl]-piperazine XII-12 VII-15 900 mg 1 h 98% ES-MS m/e: 289.1 (M + H.sup.+) [00329]embedded image 1-{3-[1-(4-Fluoro- phenyl)- cyclopropyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-15 VII-28 90 mg 2 h 96% ES-MS m/e: 299.1 (M H.sup.+) [00330]embedded image 1-[3-(4- Trifluoromethyl- phenyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-28

Intermediate XII-7; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-piperazine

[1023] ##STR00331##

[1024] To a solution of 3-benzyl-5-trichloromethyl-[1,2,4]oxadiazole VI-7 (1.46 g, 5.26 mmol) in EtOH (20 mL) was added piperazine (2.72 g, 31.6 mmol). The reaction mixture was heated to 85 C. for 4 hours, cooled down to RT, and all volatiles evaporated. The crude residue was purified on column chromatography (CH.sub.2Cl.sub.2/MeOH: 9/1) to give 0.79 g (62%) of the title product as a light yellow oil. ES-MS m/e: 245.2 (M+H.sup.+).

[1025] The following intermediates of formula XII were prepared according to the same procedure from intermediates VI previously described as shown in Table 9:

TABLE-US-00009 TABLE 9 Reaction Intermediate Scale time Yield Analysis Structure Name Intermediate VI-8 8.8 g 6 h 20% ES-MS m/e: 273.2 (M + H+) [00332]embedded image 3-(1-phenylpropyl)- 5-(piperazin-1-yl)- 1,2,4-oxadiazole XII-8 VI-9 2.448 g 2.5 h 51% ES-MS m/e: 279.1 (M + H+) [00333]embedded image 1-[3-(4-Chloro- benzyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-9 VI-10 3.0 g 2.5 h 69% ES-MS m/e: 279.2 (M + H+) [00334]embedded image 1-[3-(3-Chloro- benzyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-10 VI-11 2.448 g 2.5 h 51% ES-MS m/e: 263.5 (M + H.sup.+) [00335]embedded image 3-(4-fluorobenzyl)-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-11 VI-13 313 mg 3 h 68% ES-MS m/e: 281.2 (M + H+) [00336]embedded image 1-[3-(3,4-Difluoro- benzyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-13 VI-16 1.50 g 7 h 20% ES-MS m/e: 291.1 (M + H+) [00337]embedded image 1-{3-[1-(4-Fluoro- phenyl)-1-methyl- ethyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-16 VI-17 5.13 g o/n 47% over 2 steps ES-MS m/e: 271.3 (M + H+) [00338]embedded image 1-[3-(1-Phenyl- cyclopropyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-17 VI-18 2.54 g o/n 68% ES-MS m/e: 305.1 (M + H+) [00339]embedded image 1-{3-[1-(3-Chloro- phenyl)- cyclopropyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-18 VI-19 1.74 g 5 h 49% ES-MS m/e: 305.1 (M + H+) [00340]embedded image 1-{3-[1-(4-Chloro- phenyl)- cyclopropyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-19 VI-20 1.18 g 1 h 89% ES-MS m/e: 315.0 (M + H+) [00341]embedded image 1-{3-[(4-Chloro- phenyl)-difluoro- methyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-20 VI-21 0.55 g 2 h 89% ES-MS m/e: 299.1 (M + H+) [00342]embedded image 1-{3-[Difluoro-(4- fluoro-phenyl)- methyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-21 VI-22 0.93 g 4 h 15% ES-MS m/e: 307.2 (M + H+) [00343]embedded image 1-{3-[1-(3-Chloro- phenyl)-1-methyl- ethyl]- [1,2,4]oxadiazol-5- yl}-piperazine XII-22 VI-23 2.94 g 15 min 59% ES-MS m/e: 281.1 (M + H+) [00344]embedded image 1-[3-(Difluoro- phenyl-methyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-23 VI-24 1.5 g 4 h 20% [00345]embedded image 3- (cyclopropylmethyl)- 5-(piperazin-1-yl)- 1,2,4-oxadiazole XII-24 VI-25 1.31 g 4 h (+ o/n at 50 C.) 43% Light yellow oil [00346]embedded image 5-(piperazin-1-yl)-3- (2,2,2- trifluoroethyl)-1,2,4- oxadiazole XII-25 VI-26 320 mg 5 h 18% ES-MS m/e: 260.1 (M + H+) [00347]embedded image 1-(3-(2-Methyl- pyridin-4-ylmethyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-26 VI-27 2.6 g 1 h 65% Light yellow oil [00348]embedded image 5-(piperazin-1-yl)-3- (3,3,3- trifluoropropyl)- 1,2,4-oxadiazole XII-27 VI-29 1.2 g 30 min 37% Yellow oil [00349]embedded image 3-((1S,4R)- bicyclo[2.2.1]heptan- 2-yl)-5-(piperazin-1- yl)-1,2,4-oxadiazole XII-29 VI-30 700 mg 2 h 35% ES-MS m/e: 195.3 (M + H+) [00350]embedded image 3-cyclopropyl-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-30 VI-32 1.16 g 4 h 7% ES-MS m/e: 272.1 (M + H+) [00351]embedded image 1-[3-(1-Methyl-1- phenyl-ethyl)- [1,2,4]oxadiazol-5- yl]-piperazine XII-32

Intermediate XII-33; Ethyl 5-(piperazin-1-yl)-1,2,4-oxadiazole-3-carboxylate

[1026] In a 100 mL round-bottomed flask, ethyl 5-(trichloromethyl)-1,2,4-oxadiazole-3-carboxylate VI-33 (2.2 g, 7.63 mmol) and piperazine (3.94 g, 45.8 mmol) were combined with DMF (20 ml) to give a solution. The reaction mixture was heated to 60 C. and stirred for 30 min. The reaction mixture was poured into 300 mL EtOAc and extracted with water and brine (1100 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. Filtration on SiO.sub.2 pad gave 200 mg (11%) of title product.

[1027] The following intermediates of formula XII were prepared according to the same procedure from intermediates VI previously described as shown in Table 10:

TABLE-US-00010 TABLE 10 Reaction Intermediate Scale time Yield Analysis Structure Name Intermediate VI-34 967 mg 1 h 34% ES-MS m/e: 197.2 (M + H+) [00352]embedded image 5-(piperazin-1-yl)- 3-propyl-1,2,4- oxadiazole XII-34 VI-35 1.05 g 30 min 31% ES-MS m/e: 211.2 (M + H+) [00353]embedded image 3-butyl-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-35 VI-36 540 mg 30 min 49% ES-MS m/e: 211.2 (M + H+) [00354]embedded image 3-(tert-butyl)-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-36 VI-37 480 mg 30 min 52% [00355]embedded image 3-cyclohexyl-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-37 VI-38 280 mg 30 min ES-MS m/e: 197.2 (M + H+) [00356]embedded image 3-isopropyl-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-38 VI-39 300 mg 30 min 53% ES-MS m/e: 213.2 (M + H+) [00357]embedded image 3-(2- methoxyethyl)-5- (piperazin-1-yl)- 1,2,4-oxadiazole XII-39

Intermediate XIIa-31; 3-(2-(2-Methylpyridin-4-yl)propan-2-yl)-5-(piperazin-1-yl)-1,2,4-oxadiazole

[1028] ##STR00358##

[1029] To a 10 mL microwave vial was added 3-(2-(2-methylpyridin-4-yl)propan-2-yl)-5-(trichloromethyl)-1,2,4-oxadiazole VI-31 (110 mg, 343 mol) and piperazine (296 mg, 3.43 mmol) in DMF. The vial was capped and heated in the microwave to 130 C. for 10 min. The solvent was then evaporated and the residue poured into water and extracted with EtOAc. The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude residue was then purified by column chromatography (silica, CH.sub.2Cl.sub.2/MeOH 95:5-8:2) to yield 3-(2-(2-methylpyridin-4-yl)propan-2-yl)-5-(piperazin-1-yl)-1,2,4-oxadiazole (35 mg, 122 mol, 35.5% yield). ES-MS m/e: 288 (M+H+).

Process for Preparation Intermediates of Formula XIII

Intermediate XIII-11; 3-(4-Fluorobenzyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole bis(2,2,2-trifluoroacetate)

[1030] ##STR00359##

[1031] In a 50 mL pear-shaped flask, tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate (300 mg, 1.33 mmol) and 3-(4-fluorobenzyl)-5-(trichloromethyl)-1,2,4-oxadiazole VI-11 (470 mg, 1.59 mmol) were combined with DMF (8.84 ml) to give a light yellow solution. The reaction mixture was stirred for 18 h. iPr.sub.2NEt (171 mg, 232 l, 1.33 mmol) was added. The reaction mixture was poured into 150 mL EtOAc and extracted with sat NaHCO.sub.3 (150 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 50 g, 0-100% EtOAc in heptane) to give 83 mg (16%) of tert-butyl 2-(3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate.

[1032] This compound was dissolved in CH.sub.2Cl.sub.2 (0.33 mL) and TFA (111 L, 1.44 mmol) and the reaction mixture was stirred overnight. The crude reaction mixture was concentrated in vacuo, to give 104.6 g (4-fluorobenzyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole XIII-11, TFA salt (97% yield). ES-MS m/e: 303.3 (M+H+).

Intermediate XIII-25; 5-(2,7-Diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1033] ##STR00360##

[1034] In a 5 ml screw cap reactor, 5-(trichloromethyl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole VI-25 (150 mg, 0.557 mmol), tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate (189 mg, 0.835 mmol) and iPr.sub.2NEt (1.67 mmol, 216 mg, Eq:3) were combined with DMF. The reaction mixture was heated to 50 C. and stirred for 75 min. The crude material was purified by preparative HPLC to give 163 mg of Boc-protected material which was then stirred in CH.sub.2Cl.sub.2/TFA (4/1 ratio) at RT for 20 minutes. The solvent was evaporated under high vacuum to give title compound, which was used in the next step without further purification.

Intermediate XIII-39; 3-(2-Methoxyethyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole

[1035] ##STR00361##

[1036] 3-(2-Methoxyethyl)-5-(2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole was prepared following the same method as Intermediate XIII-25, starting from intermediate VI-39.

Process for Preparation Compounds of Formula I

General Procedure A

[1037] To a stirred solution of a piperazine intermediate XII (0.1 mmol) in CH.sub.2Cl.sub.2 (1 ml) at RT were added ethyl-diisopropyl-amine (0.2 mmol) and a sulfonyl chloride of formula ArSO.sub.2Cl (1.1 mmol). Stirring was continued until completion of the reaction. The reaction mixture was then concentrated under vacuo and purification by flash chromatography on SiO.sub.2 or preparative HPLC afforded final compounds formula (I).

General Procedure B

[1038] To a stirred solution of a piperazine intermediate XII (0.13 mol, 1 eq) in DMF (1 ml) at RT were added a derivative of formula III (0.195 mol, 1.5 eq), ethyl-diisopropyl-amine (0.26 mol, 2.0 eq). The reaction mixture was heated to 50 C. until completion of the reaction. The reaction mixture was then concentrated under vacuo and purification by flash chromatography on SiO.sub.2 or preparative HPLC afforded final compounds of formula (I).

General Procedure C

[1039] To a stirred solution of a piperazine intermediate XII (0.08 mmol) in DMF (1 mL) at RT were added ethyl-diisopropyl-amine (10 eq) and a sulfonyl chloride of formula ArSO.sub.2Cl (1.1 mmol). Stirring was continued until completion of the reaction. The reaction mixture was then concentrated under vacuo and purification by flash chromatography on SiO.sub.2 or preparative HPLC afforded final compounds of formula (I).

Example 1; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole

[1040] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-1 and 1-(bromomethyl)-2-chlorobenzene overnight.

Example 2; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole

[1041] 5-(4-(4-methylbenzyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-1 and 1-(bromomethyl)-4-methylbenzene overnight. ES-MS m/e: 335.3 (M+H.sup.+).

Example 3; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole

[1042] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-1 and 1-(2-bromoethyl)-4-chlorobenzene overnight. ES-MS m/e: 369.2 (M+H.sup.+)

Example 4; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole

[1043] 15-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-phenyl-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-1 and 4-(2-bromoethyl)-2-methoxypyridine. ES-MS m/e: 366.2 (M+H.sup.+).

Example 5; 4-{2-[4-(3-Phenyl-[1,2,4]oxadiazol-5-yl)-piperazin-1-yl]-ethyl}-morpholine

[1044] 4-{2-[4-(3-Phenyl-[1,2,4]oxadiazol-5-yl)-piperazin-1-yl]-ethyl}-morpholine was prepared according to general procedure B by reacting piperazine intermediate XII-1 and 4-(2-chloroethyl)morpholine hydrochloride. ES-MS m/e: 344.1 (M+H.sup.+).

Example 6; 5-(4-Isopentylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole

[1045] 5-(4-Isopentylpiperazin-1-yl)-3-phenyl-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-1 and 1-bromo-3-methylbutane. ES-MS m/e: 301.2 (M+H.sup.+).

Example 7; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1046] To a solution of 5-chloro-3-p-tolyl-[1,2,4]oxadiazole (as described in the synthesis of intermediate XII-2) (0.95 g, 4.88 mmol) (19.5 mg, 100 mol) in N-Methyl-2-pyrrolidinone (1 mL) was added iPr.sub.2NEt (25.8 mg, 19.1 l, 200 mot) and 1-(benzo[d][1,3]dioxol-5-ylmethyl)piperazine (33 mg, 150 mot). The reaction mixture was stirred at 175 C. for 20 minutes. After cooling down, the reaction mixture was directly purified by preparative HPLC to give 29.8 mg (78.7%) of the title product as light brown solid. ES-MS m/e: 379.4 (M+H.sup.+).

Example 8; 5-(4-(4-Chlorobenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1047] 5-(4-(4-Chlorobenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared by coupling 5-chloro-3-p-tolyl-1,2,4-oxadiazole (as described in the synthesis of intermediate XII-2) with 1-(4-chlorobenzyl)piperazine as described in Example 7. ES-MS m/e: 397.3 (M+H.sup.+).

Example 9; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1048] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-2 and 3-methoxy-1-(2-bromoethyl)benzene. ES-MS m/e: 379.4 (M+H+).

Example 10; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1049] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-2 and 2-methylbenzyl chloride. ES-MS m/e: 349.3 (M+H.sup.+).

Example 11; 5-(4-((4-(Oxazol-5-yl)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1050] 5-(4-((4-(Oxazol-5-yl)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared in 46% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-(oxazol-5-yl)benzene-1-sulfonyl chloride overnight. ES-MS m/e: 452.1 (M+H.sup.+).

Example 12; 5-(4-((4-(difluoromethoxy)phenyl) sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1051] 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared in 53% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-(difluoromethoxy)benzene-1-sulfonyl chloride overnight. ES-MS m/e: 451.3 (M+H.sup.+).

Example 13; 3-(p-Tolyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1052] 3-(p-Tolyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 42% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-(trifluoromethoxy)benzene-1-sulfonyl chloride overnight. ES-MS m/e: 469.2 (M+H+).

Example 14; 5-(4-((4-Fluorophenyl) sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1053] 5-(4-((4-Fluorophenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared in 59% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-fluorobenzene-1-sulfonyl chloride overnight. ES-MS m/e: 403.3 (M+H+).

Example 15; 5-(4-((4-Isopropylphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1054] 5-(4-((4-Isopropylphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared in 56% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-isopropylbenzene-1-sulfonyl chloride overnight. ES-MS m/e: 427.3 (M+H+).

Example 16; 3-(p-Tolyl)-5-(4-((4-(trifluoromethyl)phenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1055] 3-(p-Tolyl)-5-(4-((4-(trifluoromethyl)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 57% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-(trifluoromethyl)benzene-1-sulfonyl chloride overnight. ES-MS m/e: 453.2 (M+H+).

Example 17; 1-(4-((4-(4-(3-(p-Tolyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl) sulfonyl)phenyl)pyrrolidin-2-one

[1056] 1-(4-((4-(3-(p-Tolyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenyl)pyrrolidin-2-one was prepared in 30% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-(2-oxopyrrolidin-1-yl)benzene-1-sulfonyl chloride overnight. ES-MS m/e: 468.3 (M+H+).

Example 18; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole

[1057] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(p-tolyl)-1,2,4-oxadiazole was prepared in 62% yield according to general procedure C by reacting piperazine intermediate XII-2 with 4-methoxybenzene-1-sulfonyl chloride overnight. ES-MS m/e: 415.2 (M+H+).

Example 19; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(4-chlorophenyl)-1,2,4-oxadiazole

[1058] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(4-chlorophenyl)-1,2,4-oxadiazole was prepared to according general procedure B by reacting piperazine intermediate XII-3 with 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 403.3 (M+H.sup.+).

Example 20; 3-(4-chlorophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole

[1059] 3-(4-Chlorophenyl)-5-(4-phenethylpiperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-3 with (2-bromo-ethyl)-benzene. ES-MS m/e: 369.2 (M+H.sup.+).

Example 21; 3-(4-Chlorophenyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1060] 3-(4-Chlorophenyl)-5-(4-(3 ethoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-3 with 1-(2-bromo-ethyl)-3-methoxy-benzene. ES-MS m/e: 399.2 (M+H.sup.+).

Example 22; 3-(4-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1061] 3-(4-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-3 with 2-methylbenzyl chloride. ES-MS m/e: 369.1 (M+H.sup.+).

Example 23; 3-(4-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1062] 3-(4-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-3 with 4-(2-bromoethyl)-2-methoxypyridine. ES-MS m/e: 400.1 (M+H.sup.+).

Example 24; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole

[1063] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-4 with 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 403.3 (M+H.sup.+).

Example 25; 3-(3-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1064] 3-(3-Chlorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-4 with 4-(2-bromoethyl)-2-methoxypyridine. ES-MS m/e: 400.1 (M+H.sup.+).

Example 26; 3-(3-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1065] 3-(3-Chlorophenyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-4 with 2-methylbenzyl chloride. ES-MS m/e: 369.1 (M+H.sup.+).

Example 27; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole

[1066] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-chlorophenyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-4 with 1-(bromomethyl)-2-chlorobenzene. ES-MS m/e: 389.2 (M+H.sup.+).

Example 28; 2-{4-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-ylmethyl}-benzonitrile

[1067] 2-{4-[3-(3-Chloro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-ylmethyl}-benzonitrile was prepared according to general procedure B by reacting piperazine intermediate XII-4 with 2-(bromomethyl)benzonitrile. ES-MS m/e: 380.3 (M+H.sup.+).

Example 29; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole

[1068] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-5 with 1-(bromomethyl)-2-chlorobenzene. ES-MS m/e: 373.1 (M+H.sup.+).

Example 30; 3-(3-Fluorophenyl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1069] 3-(3-Fluorophenyl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-5 with 1-(bromomethyl)-4-methylbenzene.

Example 31; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole

[1070] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3-fluorophenyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-5 with 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 387.2 (M+H.sup.+).

Example 32; 3-(3-Fluorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1071] 3-(3-Fluorophenyl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-5 with 4-(2-bromoethyl)-2-methoxypyridine. ES-MS m/e: 384.2 (M+H.sup.+).

Example 33; 4-(2-(4-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine

[1072] 4-(2-(4-(3-(3-Fluorophenyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine was prepared according to general procedure B by reacting piperazine intermediate XII-5 and 4-(2-chloroethyl)morpholine hydrochloride.

Example 34; 3-(3-Fluorophenyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole

[1073] 3-(3-Fluorophenyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-5 and 1-bromo-3-methylbutane. ES-MS m/e: 319.1 (M+H.sup.+).

Example 35; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,4-difluorophenyl)-1,2,4-oxadiazole

[1074] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,4-difluorophenyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-6 and 1-(bromomethyl)-2-chlorobenzene. ES-MS m/e: 391.1 (M+H.sup.+).

Example 36; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1075] 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-6 and 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 405.3 (M+H.sup.+).

Example 37; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-methoxy-benzenesulfonyl)-piperazine

[1076] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-7 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 415.3 (M+H.sup.+).

Example 38; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1077] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-7 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 429.3 (M+H.sup.+).

Example 39; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1078] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-7 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 451.2 (M+H.sup.+).

Example 40; 1-Benzo[1,3]dioxol-5-ylmethyl-4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-piperazine

[1079] 1-Benzo[1,3]dioxol-5-ylmethyl-4-(3-benzyl-[1,2,4]oxadiazol-5-yl)-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-7 and 5-chloromethyl-benzo[1,3]dioxole. ES-MS m/e: 379.4 (M+H.sup.+).

Example 41; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(2-methyl-benzyl)-piperazine

[1080] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-(2-methyl-benzyl)-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-7 and 2-methylbenzyl chloride. ES-MS m/e: 350.4 (M+H.sup.+).

Example 42; 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine

[1081] 1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-7 and 1-(2-bromo-ethyl)-3-methoxy-benzene. ES-MS m/e: 379.4 (M+H.sup.+).

Example 43; 5-((4-(3-benzyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one

[1082] 5-((4-(3-benzyl-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2 (3H)-one was prepared according to general procedure B by reacting for 2 h at 40 C. piperazine intermediate XII-7 and 2-oxo-2,3-dihydro-1,3-benzoxazole-5-sulfonyl chloride. 38% yield.

Example 44; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole

[1083] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting piperazine intermediate XII-8 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 443.3 (M+H.sup.+).

Example 45; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1084] 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-8 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 457.4 (M+H.sup.+).

Example 46; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1085] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-8 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 479.2 (M+H.sup.+).

Example 47; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole

[1086] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole was prepared in 57% yield according to general procedure B by reacting for 20 h at 75 C. piperazine intermediate XII-8 and 5-(chloromethyl)benzo[d][1,3]dioxole.

Example 48; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole

[1087] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole was prepared in 29% yield according to general procedure B by reacting for 20 h at 75 C. piperazine intermediate XII-8 and 2-methylbenzyl chloride.

Example 49; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole

[1088] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylpropyl)-1,2,4-oxadiazole was prepared in 44% yield according to general procedure B by reacting for 20 h at 75 C. piperazine intermediate XII-8 and 1-(2-bromoethyl)-3-methoxybenzene.

Examples 50 and 51; 1-(4-Methoxy-benzenesulfonyl)-4-[3-((S)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine and 1-(4-Methoxy-benzenesulfonyl)-4-[3-((R)-1-phenyl-propyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1089] The two optically pure enantiomers were obtained after resolution of the racemic mixture (prepared herein above, Example 44) by preparative chiral HPLC. Column: Chiralpak AD; Solvent 40% Ethanol/Heptane. ES-MS m/e: 443.3 (M+H.sup.+) and ES-MS m/e: 443.3 (M+H.sup.+).

Example 52; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine

[1090] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-9 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 449.2 (M+H.sup.+).

Example 53; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1091] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-9 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 463.2 (M+H.sup.+).

Example 54; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1092] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-9 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 485.2 (M+H.sup.+).

Example 55; 1-Benzo[1,3]dioxol-5-ylmethyl-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1093] 1-Benzo[1,3]dioxol-5-ylmethyl-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 5-chloromethyl-benzo[1,3]dioxole. ES-MS m/e: 413.2 (M+H.sup.+).

Example 56; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine

[1094] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 1-(2-bromo-ethyl)-3-methoxy-benzene. ES-MS m/e: 413.4 (M+H.sup.).

Example 57; 5-((4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2(3H)-one

[1095] 5-((4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)benzo[d]oxazol-2 (3H)-one was prepared in 10% yield according to general procedure A by reacting for 2 h at 40 C. piperazine intermediate XII-9 and 2-oxo-2,3-dihydro-1,3-benzoxazole-5-sulfonyl chloride.

Example 58; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine

[1096] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 2-methylbenzyl chloride. ES-MS m/e: 383.4 (M+H.sup.+).

Example 59; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(4-chloro-phenyl)-ethyl]-piperazine

[1097] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(4-chloro-phenyl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 417.3 (M+H.sup.+).

Example 60; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine

[1098] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 5-(2-bromoethyl)-2-methoxypyridine. ES-MS m/e: 414.3 (M+H.sup.+).

Example 61; 3-(4-chlorobenzyl)-5-(4-(2-fluorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1099] 3-(4-chlorobenzyl)-5 fluorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 1-(bromomethyl)-2-fluorobenzene.

Example 62; 1-(2-Chloro-benzyl)-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1100] 1-(2-Chloro-benzyl)-4-[3-(4-chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared in 24% yield according to general procedure B by reacting piperazine intermediate XII-9 and 1-(bromomethyl)-2-chlorobenzene. ES-MS m/e: 403.3 (M+H.sup.+).

Example 63; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methyl-benzyl)-piperazine

[1101] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methyl-benzyl)-piperazine was prepared in 25% yield according to general procedure B by reacting piperazine intermediate XII-9 and 1-(bromomethyl)-4-methylbenzene. ES-MS m/e: 383.2 (M+H.sup.+).

Example 64; 4-{4-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-butyronitrile

[1102] 4-{4-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazin-1-yl}-butyronitrile was prepared in 14% yield according to general procedure B by reacting piperazine intermediate XII-9 and 4-bromobutanenitrile. ES-MS m/e: 346.2 (M+H.sup.+).

Example 65; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-ethoxy-ethyl)-piperazine

[1103] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-ethoxy-ethyl)-piperazine was prepared in 15% yield according to general procedure B by reacting piperazine intermediate XII-9 and 1-bromo-2-ethoxyethane. ES-MS m/e: 351.3 (M+H.sup.+).

Example 66; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-propyl-piperazine

[1104] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-propyl-piperazine was prepared in 10% yield according to general procedure B by reacting piperazine intermediate XII-9 and 1-bromopropane. ES-MS m/e: 321.2 (M+H.sup.+).

Example 67; 3-(4-Chlorobenzyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole

[1105] 3-(4-Chlorobenzyl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole was prepared in 44% yield according to general procedure B by reacting piperazine intermediate XII-9 and 1-bromo-3-methylbutane.

Example 68; 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4,4,4-trifluoro-butyl)-piperazine

[1106] 1-[3-(4-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4,4,4-trifluoro-butyl)-piperazine was prepared in 10% yield according to general procedure B by reacting piperazine intermediate XII-9 and 4-bromo-1,1,1-trifluorobutane. ES-MS m/e: 389.2 (M+H.sup.+).

Example 69; 3-(4-Chlorobenzyl)-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole

[1107] 3-(4-Chlorobenzyl)-5-(4-((tetrahydro-2H-pyran-4-yl)methyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 25% yield according to general procedure B by reacting piperazine intermediate XII-9 and 4-(bromomethyl)tetrahydro-2H-pyran.

Example 70; 4-(2-(4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine

[1108] 4-(2-(4-(3-(4-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine was prepared according to general procedure B by reacting piperazine intermediate XII-9 and 4-(2-chloroethyl)morpholine hydrochloride.

Example 71; 3-(4-Chlorobenzyl)-5-(4-isopropylpiperazin-1-yl)-1,2,4-oxadiazole

[1109] 3-(4-Chlorobenzyl)-5-(4-isopropylpiperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting overnight at 80 C. piperazine intermediate XII-9 and 2-bromopropane. ES-MS m/e: 321.2 (M+H.sup.+).

Example 72; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine

[1110] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-10 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 449.2 (M+H.sup.+).

Example 73; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1111] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-10 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 463.2 (M+H.sup.+).

Example 74; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1112] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-10 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 485.3 (M+H.sup.+).

Example 75; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine

[1113] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-10 and 2-methylbenzyl chloride. ES-MS m/e: 383.2 (M+H.sup.+).

Example 76; 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine

[1114] 1-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-10 and 1-(2-bromo-ethyl)-3-methoxy-benzene. ES-MS m/c: 413.4 (M+H.sup.+).

Example 77; 5-{4-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-3H-benzooxazol-2-one

[1115] 5-{4-[3-(3-Chloro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-3H-benzo oxazol-2-one was prepared according to general procedure A by reacting piperazine intermediate XII-10 and 2-oxo-2,3-dihydro-1,3-benzoxazole-5-sulfonyl chloride. ES-MS m/e: 476.3 (M+H.sup.+).

Example 78; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-dimethylpiperazine-1-sulfonamide

[1116] 4-(3-(3-chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-dimethylpiperazine-1-sulfonamide was prepared in 40% yield according to general procedure A by reacting piperazine intermediate XII-10 and dimethylsulfamoyl chloride.

Example 79; 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-diethylpiperazine-1-sulfon amide

[1117] 4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)-N,N-di ethylpiperazine-1-sulfonamide was prepared in 17% yield according to general procedure A by reacting piperazine intermediate XII-10 and diethylsulfamoyl chloride.

Example 80; 4-((4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)morpholine

[1118] 4-((4-(3-(3-Chlorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl) sulfonyl)morpholine was prepared in 30% yield according to general procedure A by reacting piperazine intermediate XII-10 and morpholine-4-sulfonyl chloride.

Example 81; 3-(3-Chlorobenzyl)-5-(4-(pyrrolidin-1-ylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1119] 3-(3-Chlorobenzyl)-5-(4-(pyrrolidin-1-ylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 27% yield according to general procedure A by reacting piperazine intermediate XII-10 and pyrrolidine-1-sulfonyl chloride.

Example 82; 5-(4-(Azepan-1-ylsulfonyl)piperazin-1-yl)-3-(3-chlorobenzyl)-1,2,4-oxadiazole

[1120] 5-(4-(Azepan-1-ylsulfonyl)piperazin-1-yl)-3-(3-chlorobenzyl)-1,2,4-oxadiazole was prepared in 9% yield according to general procedure A by reacting piperazine intermediate XII-10 and azepane-1-sulfonyl chloride.

Example 83; 3-(3-Chlorobenzyl)-5-(4-((4-methoxypiperidin-1-yl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1121] 3-(3-Chlorobenzyl)-5-(4-((4-methoxypiperidin-1-yl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting piperazine intermediate XII-10 and 4-methoxypiperidine-1-sulfonyl chloride.

Example 84; [3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine

[1122] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 433.1 (M+H.sup.+).

Example 85; 1-(4-Fluoro-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1123] 1-(4-Fluoro-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-fluoro-benzenesulfonyl chloride. ES-MS m/e: 421.2 (M+H.sup.+).

Example 86; N-(4-{4-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-phenyl)-acetamide

[1124] N-(4-{4-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine-1-sulfonyl}-phenyl)-acetamide was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-acetylamino-benzenesulfonyl chloride. ES-MS m/e: 460.2 (M+H.sup.+).

Example 87; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine

[1125] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-trifluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 487.1 (M+H.sup.+).

Example 88; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine

[1126] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-trifluoromethyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 3-trifluoromethyl-benzenesulfonyl. ES-MS m/e: 471.1 (M+H.sup.+).

Example 89; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(3-methyl-benzyl)-piperazine

[1127] To a solution of 1-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine XII-12 (20 mg, 76.3 mol) in DMF (1 mL) was added sodium hydride (4.03 mg, 83.9 mol). The reaction mixture was stirred at room temperature for 5 minutes, then 1-(bromomethyl)-3-methylbenzene (21.1 mg, 114 mmol) was added. The reaction mixture was stirred at 50 C. overnight. After cooling down, the reaction mixture was quenched with 200 l water. The reaction mixture was filtrated over Decalite. The crude material was purified by preparative HPLC to give 5.8 mg (20.7%) of the title product. ES-MS m/e: 367.2 (M+H.sup.+).

Example 90; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine

[1128] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-12 and 1-(2-bromoethyl)-3-methoxybenzene. ES-MS m/e: 397.3 (M+H.sup.+).

Example 91; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1129] 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 447.3 (M+H.sup.+).

Example 92; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1130] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 469.2 (M+H.sup.+).

Example 93; 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-isopropoxy-benzenesulfonyl)-piperazine

[1131] 1-[3-(3-Fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-isopropoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 4-isopropoxy-benzenesulfonyl chloride. ES-MS m/e: 461.2 (M+H.sup.+).

Example 94; 3-(4-((4-(3-(3-Fluoro benzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenoxy)propanenitrile

[1132] 3-(4-((4-(3-(3-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)sulfonyl)phenoxy)propanenitrile was prepared in 28% yield according to general procedure A by reacting piperazine intermediate XII-12 and 4-(2-cyanoethoxy)benzene-1-sulfonyl chloride.

Example 95; 1-(2,3-Dihydro-benzofuran-5-sulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1133] 1-(2,3-Dihydro-benzo furan-5-sulfonyl)-4-[3-(3-fluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-12 and 2,3-dihydro-benzofuran-5-sulfonyl chloride. ES-MS m/e: 445.2 (M+H.sup.+).

Example 96; 3-(3-Fluorobenzyl)-5-(4-((4-isopropoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1134] 3-(3-Fluorobenzyl)-5-(4-((4-isopropoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 29% yield according to general procedure A by reacting piperazine intermediate XII-12 and 4-isopropoxybenzene-1-sulfonyl chloride.

Example 97; 1-(4-Chloro-benzyl)-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

a) 3-(3,4-Difluoro-benzyl)-4H-[1,2,4]oxadiazol-5-one

[1135] To a solution of 2-(3,4-difluorophenyl)-N-(hydroxy)acetamidine V-13 (1.1 g, 5.49 mmol) in dichloromethane (5 mL), was added dropwise a solution of ethyl chloroformate (538 l, 5.6 mmol) and triethylamine (1.15 mL, 8.24 mmol). The reaction mixture was stirred at room temperature for 30 minutes. Then, it was extracted with water and dichloromethane. The organic phase was dried over Na.sub.2SO.sub.4 and concentrated under vacuo. The obtained white solid was then dissolved in toluene (10 mL). The reaction mixture was heated to reflux for 20 hours. The volatiles were removed under vacuo and a column chromatography (EtOAc/Heptane 1/1) gave the title product. ES-MS m/e: 211.1 (MH.sup.+).

b) 1-(4-Chloro-benzyl)-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1136] To a solution of 3-(3,4-difluoro-benzyl)-4H-[1,2,4]oxadiazol-5-one (50 mg, 236 mol) in DMF (1 mL) was added iPr.sub.2NEt (60.9 mg, 82.3 l, 471 mol), (1H-benzo[d][1,2,3]triazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate(V) (115 mg, 259 mol) and 1-(4-chlorobenzyl)piperazine (99.2 mg, 471 mol. The reaction mixture was stirred at 70 C. for 2 days. The volatiles were removed under vacuo, and the residue taken up in EtOAC and washed with a saturated aqueous solution of NaHCO.sub.3, followed by a HCl 0.1N solution. The organic phase was dried over Na.sub.2SO.sub.4, concentrated under vacuo, and a column chromatography (EtOAc/Heptane 1/2) gave the title product. ES-MS m/e: 405.3 (M+H.sup.+).

Example 98; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine

[1137] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(3-methoxy-phenyl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-13 and 1-(2-bromoethyl)-3-methoxybenzene. ES-MS m/e: 415.4 (M+H.sup.+).

Example 99; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine

[1138] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-13 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 451.1 (M+H.sup.+).

Example 100; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1139] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-ethoxy-benzene sulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-13 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 465.3 (M+H.sup.+).

Example 101; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1140] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-13 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 487.2 (M+H.sup.+).

Example 102; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1141] 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(3,4-difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-13 and 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 419.2 (M+H.sup.+).

Example 103; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine

[1142] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-[2-(6-methoxy-pyridin-3-yl)-ethyl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-13 and 4-(2-bromoethyl)-2-methoxypyridine. ES-MS m/e: 416.3 (M+H.sup.+).

Example 104; 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine

[1143] 1-[3-(3,4-Difluoro-benzyl)-[1,2,4]oxadiazol-5-yl]-4-(2-methyl-benzyl)-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-13 and 2-methylbenzyl chloride. ES-MS m/c: 385.2 (M+H).

Example 105; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1144] 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-15 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 459.2 (M+H.sup.+).

Example 106; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-piperazine

[1145] 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-15 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 473.2 (M+H.sup.+).

Example 107; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-((4-(trifluoromethoxy)phenyl)sulfonyl) piperazin-1-yl)-1,2,4-oxadiazole

[1146] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-((4-(trifluoromethoxy)phenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting piperazine intermediate XII-15 and 4-(trifluoromethoxy)benzene-1-sulfonyl chloride.

Example 108; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1147] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-15 and 1-(chloromethyl)-2-methylbenzene.

Example 109; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1148] 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-15 and 1-(2-bromoethyl)-3-methoxybenzene.

Example 110; 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1149] 1-{3-[1-(4-Fluoro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-15 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 475.3 (M+H.sup.+).

Example 111; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole

[1150] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole was prepared according general to procedure B by reacting piperazine intermediate XII-15 and 1-(2-bromoethyl)-4-chlorobenzene.

Example 112; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole

[1151] 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-(4-fluorophenyl)cyclopropyl)-1,2,4-oxadiazole 1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-15 and 5-(bromomethyl)-2,2-difluorobenzo[d][1,3]dioxole.

Example 113; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1152] 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-16 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 461.3 (M+H.sup.+).

Example 114; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine

[1153] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-16 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 497.2 (M+H.sup.+).

Example 115; 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl][1,2,4]oxadiazol-5-yl}-piperazine

[1154] 1-(4-Ethoxy-benzenesulfonyl)-4-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-16 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 475.2 (M+H.sup.+).

Example 116; 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1155] 1-{3-[1-(4-Fluoro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-16 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 477.1 (M+H.sup.+).

Example 117; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1156] 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(2-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-16 and 2-methylbenzyl chloride.

Example 118; 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1157] 3-(2-(4-Fluorophenyl)propan-2-yl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-16 and 1-(2-bromoethyl)-3-methoxybenzene.

Example 119; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-(4-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole

[1158] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(2-(4-fluorophenyl)propan-2-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-16 and 5-(bromomethyl)benzo[d][1,3]dioxole.

Example 120; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1159] 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-17 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 441.3 (M+H.sup.+).

Example 121; 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1160] 1-(4-Ethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-17 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 455.4 (M+H.sup.+).

Example 122; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1161] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-17 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 477.3 (M+H.sup.+).

Example 123; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1162] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 2-methylbenzyl chloride.

Example 124; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1163] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 5-(bromomethyl)benzo[d][1,3]dioxole.

Example 125; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1164] 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 1-(2-bromoethyl)-3-methoxybenzene.

Example 126; 1-(4-Methylsulfanyl-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1165] 1-(4-Methylsulfanyl-benzenesulfonyl)-4-[3-(1-phenyl-cyclopropyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-17 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 457.3 (M+H.sup.+).

Example 127; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1166] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 1-(2-bromoethyl)-4-chlorobenzene.

Example 128; 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1167] 5-(4-((2,2-Difluorobenzo[d][1,3]dioxol-5-yl)methyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 5-(bromomethyl)-2,2-difluorobenzo[d][1,3]dioxole.

Example 129; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1168] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 1-(bromomethyl)-2-chlorobenzene.

Example 130; 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1169] 5-(4-(4-Methylbenzyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 1-(bromomethyl)-4-methylbenzene.

Example 131; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(1-phenyl cyclopropyl)-1,2,4-oxadiazole

[1170] 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 4-(2-bromoethyl)-2-methoxypyridine.

Example 132; 4-(2-(4-(3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine

[1171] 4-(2-(4-(3-(1-Phenylcyclopropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 4-(2-chloroethyl)morpholine hydrochloride.

Example 133; 5-(4-Isopentylpiperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole

[1172] 5-(4-Isopentylpiperazin-1-yl)-3-(1-phenylcyclopropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-17 and 1-bromo-3-methylbutane.

Example 134; 1-[3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine

[1173] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-18 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 475.3 (M+H.sup.+).

Example 135; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1174] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-18 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 489.3 (M+H.sup.+).

Example 136; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1175] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-18 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 511.2 (M+H.sup.+).

Example 137; 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1176] 1-{3-[1-(3-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-18 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 491.2 (M+H.sup.+).

Example 138; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1177] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-19 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 475.3 (M+H.sup.+).

Example 139; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1178] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-19 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 489.3 (M+H.sup.+).

Example 140; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1179] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-19 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 511.3 (M+H.sup.+).

Example 141; 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1180] 1-{3-[1-(4-Chloro-phenyl)-cyclopropyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-19 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 491.2 (M+H.sup.+).

Example 142; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1181] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-20 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 485.2 (M+H.sup.+).

Example 143; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1182] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-20 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 499.2 (M+H.sup.+).

Example 144; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1183] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-20 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 521.2 (M+H.sup.+).

Example 145; 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1184] 1-{3-[(4-Chloro-phenyl)-difluoro-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-20 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 501.2 (M+H.sup.+).

Example 146; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1185] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-21 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 469.3 (M+H.sup.+).

Example 147; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1186] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-21 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 483.3 (M+H.sup.+).

Example 148; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1187] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-21 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 505.3 (M+H.sup.+).

Example 149; 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(difluoro(4-fluorophenyl)methyl)-1,2,4-oxadiazole

[1188] 5-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-3-(difluoro (4-fluorophenyl)methyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-21 and 5-(bromomethyl)benzo[d][1,3]dioxole.

Example 150; 3-(Difluoro(4-fluorophenyl)methyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1189] 3-(difluoro (4-fluorophenyl)methyl)-5-(4-(3-methoxyphenethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-21 and 1-(2-bromo-ethyl)-3-methoxy-benzene.

Example 151; 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1190] 1-{3-[Difluoro-(4-fluoro-phenyl)-methyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-21 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 485.3 (M+H.sup.+).

Example 152; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1191] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzene sulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-22 and 4-methoxy-benzenesulfonyl-chloride. ES-MS m/e: 477.0 (M+H.sup.+).

Example 153; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine

[1192] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-ethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-22 and 4-ethoxy-benzenesulfonyl chloride. ES-MS m/e: 491.3 (M+H.sup.+).

Example 154; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine

[1193] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-difluoromethoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-22 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 513.0 (M+H.sup.+).

Example 155; 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1194] 1-{3-[1-(3-Chloro-phenyl)-1-methyl-ethyl]-[1,2,4]oxadiazol-5-yl}-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-22 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 493.2 (M+H.sup.+).

Example 156; 1-{3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl}-4-(4-methoxy-benzenesulfonyl)-piperazine

[1195] 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methoxy-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-23 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 450.9 (M+H.sup.+).

Example 157; 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine

[1196] 1-[3-(Difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-4-(4-methylsulfanyl-benzenesulfonyl)-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-23 and 4-methylsulfanyl-benzenesulfonyl chloride. ES-MS m/e: 467.5 (M+H.sup.+).

Example 158; 1-(4-Difluoro methoxy-benzenesulfonyl)-4-[3-(difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1197] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(difluoro-phenyl-methyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-23 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/e: 487.2 (M+H.sup.+).

Example 159; 3-(Cyclopropylmethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1198] 3-(Cyclopropylmethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 21% yield according to general procedure A by reacting piperazine intermediate XII-24 and 4-methoxy-benzenesulfonyl chloride.

Example 160; 3-(Cyclopropylmethyl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1199] 3-(Cyclopropylmethyl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 38% yield according to general procedure A by reacting piperazine intermediate XII-24 and 4-difluoromethoxy-benzenesulfonyl chloride.

Example 161; 3-(Cyclopropylmethyl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1200] 3-(Cyclopropylmethyl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 48% yield according to general procedure A by reacting piperazine intermediate XII-24 and 4-methylsulfanyl-benzenesulfonyl chloride.

Example 162; 3-(Cyclopropylmethyl)-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1201] 3-(Cyclopropylmethyl)-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 12% yield according to general procedure A by reacting piperazine intermediate XII-24 and 4-ethoxy-benzenesulfonyl chloride.

Example 163; 5-(4-(3-Methoxyphenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1202] 5-(4-(3-Methoxyphen ethyl)piperazin-1-yl)-3 fluoroethyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-25 and 1-(2-bromo-ethyl)-3-methoxy-benzene.

Example 164; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1203] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-25 and 1-(2-bromoethyl)-4-chlorobenzene.

Example 165; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1204] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared in 27% yield according to general procedure A by reacting piperazine intermediate XII-25 and 4-methoxy-benzenesulfonyl chloride.

Example 166; 5-(4-((4-Ethoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1205] 5-(4-((4-Ethoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared in 16% yield according to general procedure A by reacting piperazine intermediate XII-25 and 4-ethoxy-benzenesulfonyl chloride.

Example 167; 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1206] 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared in 12% yield according to general procedure A by reacting piperazine intermediate XII-25 and 4-difluoromethoxy-benzenesulfonyl chloride.

Example 168; 5-(4-((4-(4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1207] 5-(4-((4-(Methylthio)phenyl) sulfonyl)piperazin-1-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared in 30% yield according to general procedure A by reacting piperazine intermediate XII-25 and 4-methylsulfanyl-benzenesulfonyl chloride.

Example 169; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(2-methyl-pyridin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1208] 1-(4-Methoxy-benzenesulfonyl)-4-[3-(2-methyl-pyridin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-26 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 430.3 (M+H.sup.+).

Example 170; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-((2-methylpyridin-4-yl)methyl)-1,2,4-oxadiazole

[1209] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(2-methylpyridin-4-yl)methyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-26 and 1-(2-bromoethyl)-4-chlorobenzene.

Example 171; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1210] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting piperazine intermediate XII-27 and 4-methoxy-benzenesulfonyl chloride.

Example 172; 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1211] 5-(4-((4-(Methylthio)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting piperazine intermediate XII-27 and 4-methylsulfanyl-benzenesulfonyl chloride.

Example 173; 5-(4-((4-(Difluoro methoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1212] 5-(4-((4-(Difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-3-(3,3,3-tri fluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting piperazine intermediate XIIa-27 and 4-difluoromethoxy-benzenesulfonyl chloride.

Example 174; 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1213] 5-(4-(4-Chlorophenethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 1-(2-bromoethyl)-4-chlorobenzene.

Example 175; 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1214] 5-(4-(2-(2-Methoxypyridin-4-yl)ethyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 4-(2-bromoethyl)-2-methoxypyridine.

Example 176; 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1215] 5-(4-(2-Methylbenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 2-methylbenzyl chloride.

Example 177; 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1216] 5-(4-(2-Chlorobenzyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 1-(bromomethyl)-2-chlorobenzene.

Example 178; 2-((4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile

[1217] 2-((4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)methyl)benzonitrile was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 2-(bromomethyl)benzonitrile.

Example 179; 5-(4-Isopentylpiperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1218] 5-(4-Isopentylpiperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 1-bromo-3-methylbutane.

Example 180; 4-(2-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine

[1219] 4-(2-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 4-(2-chloroethyl)morpholine hydrochloride.

Example 181; 4-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)butanenitrile

[1220] 4-(4-(3-(3,3,3-Trifluoropropyl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)butanenitrile was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 4-bromobutanenitrile.

Example 182; 5-(4-((6-Methylpyridin-2-yl)methyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole

[1221] 5-(4-((6-Methylpyridin-2-yl)methyl)piperazin-1-yl)-3-(3,3,3-trifluoropropyl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-27 and 2-(chloromethyl)-6-methylpyridine.

Example 183; 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1222] 1-[2-(4-Chloro-phenyl)-ethyl]-4-[3-(4-trifluoromethyl-phenyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure B by reacting piperazine intermediate XII-28 and 1-(2-bromoethyl)-4-chlorobenzene. ES-MS m/e: 437.1 (M+H.sup.+).

Example 184; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5 chlorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1223] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-chlorobenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-29 and 1-(bromomethyl)-2-chlorobenzene.

Example 185; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole

[1224] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5 methylbenzyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-29 and 1-(bromomethyl)-4-methylbenzene.

Example 186; 3-41S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-chlorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1225] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(4-chlorophenethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-29 and 1-(2-bromoethyl)-4-chlorobenzene.

Example 187; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole

[1226] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-(2-(2-methoxypyridin-4-yl)ethyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XIIa-29 and 4-(2-bromoethyl)-2-methoxypyridine.

Example 188; 4-(2-(4-(3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine

[1227] 4-(2-(4-(3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-1,2,4-oxadiazol-5-yl)piperazin-1-yl)ethyl)morpholine was prepared according to general procedure B by reacting piperazine intermediate XII-29 and 4-(2-chloroethyl)morpholine hydrochloride.

Example 189; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole

[1228] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-isopentylpiperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure B by reacting piperazine intermediate XII-29 and 1-bromo-3-methylbutane.

Example 190; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1229] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure C by reacting piperazine intermediate XII-29 and 4-methoxybenzene-1-sulfonyl chloride.

Example 191; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(methylthio)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1230] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(methylthio)phenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure C by reacting piperazine intermediate XII-29 and 4-(methylthio)benzene-1-sulfonyl chloride.

Example 192; 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl) piperazin-1-yl)-1,2,4-oxadiazole

[1231] 3-((1S,4R)-bicyclo[2.2.1]heptan-2-yl)-5-(4-((4-(difluoromethoxy)phenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared according to general procedure C by reacting piperazine intermediate XII-29 and 4-(difluoromethoxy)benzene-1-sulfonyl chloride.

Example 193; 3-Cyclopropyl-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1232] 3-Cyclopropyl-5-(4-((4-ethoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 49% yield according to general procedure A by reacting piperazine intermediate XII-30 and 4-ethoxybenzene-1-sulfonyl chloride. ES-MS m/e: 379 (M+H.sup.+).

Example 194; 3-Cyclopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1233] 3-Cyclopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 51% yield according to general procedure A by reacting piperazine intermediate XII-30 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 365 (M+H.sup.+).

Example 195; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2-(2-methylpyridin-4-yl)propan-2-yl)-1,2,4-oxadiazole

[1234] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(2-(2-methylpyridin-4-yl)propan-2-yl)-1,2,4-oxadiazole was prepared in 5% yield according to general procedure A by reacting piperazine intermediate XII-31 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 458 (M+H.sup.+).

Example 196; 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1235] 1-(4-Difluoromethoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-32 and 4-difluoromethoxy-benzenesulfonyl chloride. ES-MS m/c: 479.4 (M+H.sup.1).

Example 197; 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine

[1236] 1-(4-Methoxy-benzenesulfonyl)-4-[3-(1-methyl-1-phenyl-ethyl)-[1,2,4]oxadiazol-5-yl]-piperazine was prepared according to general procedure A by reacting piperazine intermediate XII-32 and 4-methoxy-benzenesulfonyl chloride. ES-MS m/e: 443.3 (M+H.sup.+).

Example 198; (5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl) methanol

[1237] In a 50 mL pear-shaped flask, ethyl 5-(piperazin-1-yl)-1,2,4-oxadiazole-3-carboxylate IIa-33 (200 mg, 884 mol), iPr.sub.2NEt (137 mg, 185 l, 1.06 mmol) and 4-methoxybenzene-1-sulfonyl chloride (192 mg, 928 mol) were combined with CH.sub.2Cl.sub.2 (10 ml) to give a colorless solution. The reaction mixture was stirred for 2 h at RT. The reaction mixture was poured into 50 mL CH.sub.2Cl.sub.2 and extracted with water (125 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude material was purified by chromatography (silica gel, factor 50, EtOAc/Heptane=1/1 (rf=0.2)) to give 78 mg of ethyl 5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole-3-carboxylate. ES-MS m/e: 397.2 (M+H+).

[1238] This carboxylate was combined with THF (4 ml) to give a colorless solution. The solution was cooled down to 0 C. under inert conditions. Lithium aluminum hydride (7.18 mg, 189 mol) was added portion-wise over 30 min. Reaction was quenched with water and the reaction mixture was poured into 25 mL EtOAc and extracted with water (115 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude was triturated in diethyl ether (2) and the mother liquors were removed to give 40 mg (60%) of title compounds as a white powder. ES-MS m/e: 355.2 (M+H+).

Example 199; 3-(Methoxymethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1239] In a 5 mL round-bottomed flask, (5-(4-(4-methoxyphenylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol (Example 198, 35 mg, 98.8 mol) was combined with DMF (2 ml) to give a colorless solution. It was cooled down to 0 C. under inert conditions. Sodium hydride (4.98 mg, 104 mol) was added. The reaction mixture was stirred for 3 min; then, iodomethane (15.4 mg, 6.79 l, 109 mol) was added. After 30 min, the reaction mixture was poured into 20 mL CH.sub.2Cl.sub.2 and extracted with water (115 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude was taken in diethyl ether/heptane (5/1) and sonicated. The mother liquors were removed and the remaining white solid was dried under high vacuum to give 28 mg (77%) of title compound as a white powder. ES-MS m/e: 369.2 (M+H+).

Example 200; 3-((4-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1240] In a 5 mL screw cap reactor, triphenylphosphine on resin (57.0 mg, 217 mol) was combined with THF (0.5 mL) to give a yellow suspension. A solution of 4-chlorophenol (19 mg, 148 mol) and di-tert-butyl azodicarboxylate (36.4 mg, 158 mol, Eq: 1.6) in THF (0.5 mL) was added. After 3 min, a clear solution of (5-(4-(4-methoxyphenylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol (Example 198, 35 mg, 98.8 mol) in THF (2 mL) was added. The reaction mixture was stirred at room temperature over the night. The reaction mixture was filtered and the filtrate was concentrated under vacuum. The crude material was then taken in DMF and purified by Prep. HPLC to give title compound.

Example 201; 3-((3-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1241] 3-((3-Chlorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared as described for example 200 replacing 4-chlorophenol by 3-chlorophenol.

Example 202; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(phenoxymethyl)-1,2,4-oxadiazole

[1242] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-(phenoxymethyl)-1,2,4-oxadiazole was prepared as described for example 200 replacing 4-chlorophenol by phenol.

Example 203; 3-((Cyclopropylmethoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1243] (5-(4-(4-Methoxyphenylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methanol (Example 198, 20 mg, 56 mol) was dissolved in acetone (1.5 mL) and lithium chloride was added (9.5 mg, 226 mol). The mixture was stirred at room temperature overnight to give 3-(chloromethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole.

[1244] In a 5 mL round-bottomed flask, cyclopropylmethanol (4.04 mg, 56.1 pump and sodium hydride (2.94 mg, 61.2 mot) were combined with DMF (1 ml) to give a suspension. After 2 min, a solution of 3-(chloromethyl)-5-(4-(4-methoxyphenylsulfonyl)piperazin-1-yl)-1,2,4-oxadiazole (19 mg, 51.0 mol) in 0.5 mL DMF was added. The reaction mixture was stirred at RT for 60 min. The reaction was quenched with water. The reaction mixture was poured into 15 mL EtOAc and extracted with sat NH.sub.4Cl (115 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude material was purified by chromatography (silica gel, factor 70, EtOAc/Heptane=1/2) to give (8 mg, 36%) of title compound as a white solid. ES-MS m/c: 409.3 (M+H+).

Example 204; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-((pyridin-3-yloxy)methyl)-1,2,4-oxadiazole

[1245] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-((pyridin-3-yloxy)methyl)-1,2,4-oxadiazole was prepared as described for example 200 replacing 4-chlorophenol by pyridin-3-ol.

Example 205; 4-((5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methoxy)benzonitrile

[1246] 4-((5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazol-3-yl)methoxy)benzonitrile was prepared as described for example 200 replacing 4-chlorophenol by 4-hydroxybenzonitrile.

Example 206; 3-((4-Fluorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1247] 3-((4-Fluorophenoxy)methyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared as described for example 200 replacing 4-chlorophenol by 4-fluorophenol.

Example 207; 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-propyl-1,2,4-oxadiazole

[1248] 5-(4-((4-Methoxyphenyl)sulfonyl)piperazin-1-yl)-3-propyl-1,2,4-oxadiazole was prepared in 68% yield according to general procedure A by reacting piperazine intermediate XII-34 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 367.2 (M+H+).

Example 208; 3-Butyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1249] 3-Butyl-5-(4-((4-methoxyphenyl) sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 77% yield according to general procedure A by reacting piperazine intermediate XII-35 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 381.3 (M+H+).

Example 209; 3-(Tert-butyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1250] 3-(Tert-butyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 74% yield according to general procedure A by reacting piperazine intermediate XII-36 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 381.3 (M+H+).

Example 210; 3-Cyclohexyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1251] 3-Cyclohexyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 52% yield according to general procedure A by reacting piperazine intermediate XII-37 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 407.3 (M+H+).

Example 211; 3-Isopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1252] 3-Isopropyl-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 43% yield according to general procedure A by reacting piperazine intermediate XII-38 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 367.2 (M+H+).

Example 212; 3-(2-Methoxyethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole

[1253] 3-(2-Methoxyethyl)-5-(4-((4-methoxyphenyl)sulfonyl)piperazin-1-yl)-1,2,4-oxadiazole was prepared in 27% yield according to general procedure A by reacting piperazine intermediate XII-39 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 383.2 (M+H+).

Example 213; 3-(1-(4-Fluorophenyl)cyclopropyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole

[1254] In a 50 mL, pear-shaped flask, tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate (2.5 g, 11.0 mmol), 4-methoxybenzene-1-sulfonyl chloride (2.28 g, 11.0 mmol) and iPr.sub.2NEt (2.14 g, 2.84 ml, 16.6 mmol) were combined with CH.sub.2Cl.sub.2 (73.6 ml). The reaction mixture was stirred for 1 h. The reaction mixture was then poured into CH.sub.2Cl.sub.2 and extracted with water. The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 120 g, 10% to 50% EtOAc in heptane) to give 2.965 g (68%) of tert-butyl 7-(4-methoxyphenylsulfonyl)-2,7-diazaspiro[3.5]nonane-2-carboxylate. ES-MS m/e: 397.3 (M+H+).

[1255] In a 250 mL pear-shaped flask, tert-butyl 7-(4-methoxyphenylsulfonyl)-2,7-diazaspiro[3.5]nonane-2-carboxylate (2.965 g, 7.48 mmol) was combined with CH.sub.2Cl.sub.2 (18 ml). TFA (8.53 g, 5.73 ml, 74.8 mmol) was added and the reaction mixture was stirred for 90 min. The crude reaction mixture was concentrated in vacuo.

[1256] Diethyl ether was added and evaporated to give 7-(4-methoxyphenylsulfonyl)-2,7-diazaspiro[3.5]nonane 2,2,2-trifluoroacetate as a white solid. ES-MS m/e: 297.4 (M+H+).

[1257] In a 5 mL round-bottomed flask, intermediate VIII-15 (40 mg, 182 mol), 7-(4-methoxyphenylsulfonyl)-2,7-diazaspiro[3.5]nonane 2,2,2-trifluoroacetate (149 mg, 363 mol) and iPr.sub.2NEt (168 mg, 228 l, 1.3 mmol) were combined with DMF (1.38 ml) to give a colorless solution. After 5 min stirring at RT, BOP (159 mg, 358 mol) was added. The reaction mixture was heated to 50 C. and stirred for 2 h. The reaction mixture was poured into 50 mL, EtOAc and extracted with sat NaHCO.sub.3 (115 mL). The organic layers were washed with sat NH.sub.4Cl (110 mL). The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The crude material was purified by prep. HPLC to give 9.4 mg (10%) of title compound as a white powder. ES-MS m/e: 499.1 (M+H+).

Example 214; 5-(7-((4-Methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1258] 5-(7-((4-Methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting intermediate XIII-25 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 447.2 (M+H+).

Example 215; 5-(7-((4-(Methylthio)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1259] 5-(7-((4-(Methylthio)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting intermediate XIII-25 and 4-(methylthio)benzene-1-sulfonyl chloride. ES-MS m/e: 463.2 (M+H+).

Example 216; 5-(7-((4-Ethoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1260] 5-(7-((4-Ethoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting intermediate XIII-25 and 4-ethoxybenzene-1-sulfonyl chloride. ES-MS m/e: 461.3 (M+H+).

Example 217; 5-(7-((4-(Difluoromethoxy)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole

[1261] 5-(7-((4-(Difluoromethoxy)phenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-3-(2,2,2-trifluoroethyl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting intermediate XIII-25 and 4-(difluoromethoxy)benzene-1-sulfonyl chloride. ES-MS m/e: 483.2 (M+H+).

Example 218; (3-(4-Fluorobenzyl)-1,2,4-oxadiazol-5-yl)(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methanone

[1262] In a 25 mL pear-shaped flask, 7-(4-methoxyphenylsulfonyl)-2,7-diazaspiro[3.5]nonane TFA (as prepared in example 213, 300 mg, 731 mol) and iPr.sub.2NEt (283 mg, 383 l, 2.19 mmol) were combined with EtOH (4 ml) to give a white suspension. 3-(4-fluorobenzyl)-5-(trichloromethyl)-1,2,4-oxadiazole (VI-11, 216 mg, 731 mol) was added. The reaction mixture was heated to 70 C. and stirred for 6 h.

[1263] On heating the cloudy suspension changed to a clear solution and then to an orange solution. A further 0.5 eq (80 mg) oxadiazole was added and the reaction was stirred at RT overnight. A further 0.5 eq (80 mg) oxadiazole was added and the reaction was stirred at RT for 3 h and then at 70 for 1.5 h. The reaction mixture was poured into EtOAc and extracted with water. The organic layers were dried over Na.sub.2SO.sub.4 and concentrated in vacuo to give 710 mg of dark brown semisolid. The crude material was purified by flash chromatography (silica gel, 20 g, 15% to 70% EtOAc in heptane to give 81 mg (22%) of (3-(4-fluorobenzyl)-1,2,4-oxadiazol-5-yl) (7-(4-methoxyphenylsulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)methanone. ES-MS m/e: 501.2 (M+H+).

Example 219; 3-(4-Fluorobenzyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole

[1264] 3-(4-Fluorobenzyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole was prepared in 21% yield according to general procedure A by reacting intermediate XIII-11 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 473.2 (M+H+).

Example 220; 3-(2-Methoxyethyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole

[1265] 3-(2-Methoxyethyl)-5-(7-((4-methoxyphenyl)sulfonyl)-2,7-diazaspiro[3.5]nonan-2-yl)-1,2,4-oxadiazole was prepared according to general procedure A by reacting intermediate XIII-39 and 4-methoxybenzene-1-sulfonyl chloride. ES-MS m/e: 383.0 (M+H+).

Example 221; Use of a Rat Insulinoma Cell Line Exposed to Extracellular Stressors as a Model for Beta Cell Stress/Apoptosis

[1266] The INS-1E cell line, a rat insulinoma cell line, has been characterized extensively. INS-1E cells respond to glucose by secreting insulin and, unlike most other immortalized -cell lines, they do this in a consistent manner over time. The cells are sensitive to hyperglycemia-, free fatty acid (FFA)-, and cytokine-induced stress. Prolonged stress ultimately leads to induction of apoptotic pathways and, if stress is not counter-acted, to apoptosis. Caspase-3 and -7 play a central role downstream where various apoptotic pathways merge. As such, activation (i.e. cleavage) of these caspases forms a relevant primary read-out to evaluate protective activity of compounds against stress-induced apoptosis.

[1267] To evaluate the efficacy of different compounds to prevent induction of apoptosis, an in vitro screen was developed in which INS-1E cells were exposed to a cytokine mix (IFN-, 5 ng/ml; IL-113, 20 pg/ml; TNF-, 0.25 ng/ml). The degree of induction of apoptosis was evaluated using a substrate for cleaved caspase-3 and -7, i.e. a proluminescent caspase-3/7 DEVD aminoluciferin substrate with a thermostable luciferase (Caspase-Glo 3/7 assay; Promega, cat. G8092).

Experimental Procedure:

[1268] On day 0, INS-1E cells were plated in a white-walled 96-well microplate (Greiner, cat. 655098) at 20,000 cells per well in 100 l complete medium (RPMI containing 11 mM glucose supplemented with 5% FCS, 100 IU/ml penicillin, 100 g/ml streptomycin, 10 mM HEPES, 1 mM Sodium Pyruvate and 50 M 2-Mercapto-ethanol). On day 2, 100 l medium containing cytokines and compound dissolved in DMSO was added to the cells. Wells without cytokines containing DMSO and wells with cytokines and DMSO were included to evaluate the degree of caspase 3/7 activation by the cytokinc mix. After 24 hours exposure to cytokines and/or compound, Caspase-Glo 3/7 reagent was added to the cells and caspase activity was determined by measuring luminescence.

[1269] To evaluate compound efficacy, the toxicity window was calculated by subtracting caspase activity of wells without stressor from activity of wells with stressor but without compound. The amount of caspase activity in the latter wells was normalized to 1 and used as reference. Subsequently, caspase activity in the wells with stressor and varying concentrations of compound was calculated relative to the wells without compound. Plotting caspase activity vs the log 10 of the concentration of compound permitted calculation of the EC.sub.50 values for the compounds which typically lied between 0,0001 and 10 M. Compounds with an EC.sub.50<10 M were considered active.

[1270] The EC.sub.50 values of compounds of the invention on the stress induced beta cells apoptosis model are shown in Table11 as CYT EC.sub.50 Table 11:

TABLE-US-00011 TABLE 11 Compound CYT EC.sub.50 (M) Cmpd105 0.027 Cmpd106 0.099 Cmpd110 0.010 Cmpd113 0.001 Cmpd116 0.026 Cmpd120 0.040 Cmpd121 0.186 Cmpd122 0.043 Cmpd126 0.028 Cmpd134 0.016 Cmpd135 0.129 Cmpd136 0.024 Cmpd137 0.009 Cmpd141 0.019 Cmpd145 0.082 Cmpd146 0.075 Cmpd151 0.041 Cmpd157 0.498 Cmpd191 0.554 Cmpd195 0.052 Cmpd203 0.153 Cmpd206 0.189 Cmpd213 0.010 Cmpd214 0.055 Cmpd215 0.145

Example 222; Use of -Synuclein Expressing Cells as a Model for Neuronal Degeneration Construction of an -Synuclein Over-Expressing Cell Line

[1271] A -synuclein expression plasmid was constructed by subcloning the NcoI/XhoI fragment from 212T-SYN(WT) (Griffioen et al., Biochem Biophys Acta (2006) 1762(3):312-318) containing the cDNA of human wild type -synuclein correspondingly into a standard mammalian expression vector pcDNA3.1 resulting in plasmid pcDNA3.1-SYNwt. Plasmids pcDNA3.1 and pcDNA3.1-SYNwt were transfected into human neuroblastoma cells (BE-M17; ATCC No. CRL2267) using lipofectamine reagent and subsequently, independent clonal cell lines with the plasmids stably integrated into the genome were selected by antibiotic resistance selection (Geneticin (G418)), resulting in cell lines M17.pcDNA3 and M17_3 SYN. Overexpression of -synuclein in the M17_3 SYN cell line was confirmed by Western blot analysis.

Use of -Synuclein Expressing Cells as a Model for Neuronal Degeneration

[1272] Due to the high levels of -synuclein, M17_3 SYN cells were sensitive to paraquat, a well-known risk factor Parkinson's disease and of synuclein-dependent neuronal degeneration. Cytotoxicity of cells was measured by quantification of lactate dehydrogenase (LDH) levels. In dead cells, LDH leaked out of the cells into the medium due to a loss of plasma-membrane integrity.

Experimental Procedure:

[1273] Three days preceding the experiment, primary pre-cultures of M17.pcDNA3 (as possible control) and M17_3 SYN cells were prepared, starting from a stock culture, at a density of 20.000-40.000 cells/cm2 in culture medium (Opti-MEM Reduced Serum Medium with Phenol Red (Invitrogen, Cat. 31985-047) supplemented with 10% FCS, 1 mM sodium pyruvate, 1NEAA, 500 g/ml G418 and 0.5 antibiotic/antimycotic (ABAM)). 3 days later these primary pre-cultures were used as a starting point to make secondary pre-cultures at a density of 50.000-100.000 cells/cm.sup.2. At the day of the experiment these secondary precultures were diluted to 0.5.106 cells/ml in detection medium (Opti-MEM Reduced-Serum Medium without Phenol Red (Invitrogen, Cat. 11085-021) supplemented with 10% FCS, 1 mM sodium pyruvate, 1NEAA, 500 g/ml G418 and 0,5ABAM) and 60 L of this suspension was dispensed per well into a 96-well microtiter plate. After 3 hours of incubation at 37 C./5% CO.sub.2 an equal volume of detection medium containing a final concentration of 6 mM Paraquat was added and subsequently incubated for 2 days at 37 C./5% CO.sub.2. Then LDH activity was determined using the Promega Cytotox 96 Non-Radioactive cytotoxicity assay (Promega, Cat. G1780), according to the manufacturer's instructions. Cytotoxicity was defined as the ratio of LDH relative to the total LDH in the cells and supernatant.

Use of the Neuroblastoma -Synucleinopathy Model to Screen Compounds

[1274] The assay described above using the M17_3 SYN cell line allowed screening compounds for their ability to decrease cytotoxicity in PQ-challenged cells. Compounds of the invention were tested for their ability to decrease toxicity at different concentrations, ranging from low non-effective concentrations to high effective concentrations. Afterwards, a dose-dependent inhibition curve was used to calculate the EC.sub.50. A compound was considered to be active in this test when it inhibited toxicity by more than 20% relative to untreated M17_3 SYN cells at a concentration of 10 M or lower.

[1275] The EC.sub.50 values of toxicity inhibition of the compounds of the invention using the M17_3SYN cells are shown in Table 12 as SYN EC.sub.50

TABLE-US-00012 TABLE 12 Compound SYN EC.sub.50 (M) Cmpd016 0.009 Cmpd037 0.003 Cmpd038 0.013 Cmpd039 0.011 Cmpd044 0.015 Cmpd045 0.018 Cmpd046 0.059 Cmpd050 0.068 Cmpd051 0.046 Cmpd052 0.024 Cmpd053 0.031 Cmpd054 0.019 Cmpd072 0.003 Cmpd073 0.033 Cmpd074 0.010 Cmpd077 0.139 Cmpd084 0.005 Cmpd085 0.250 Cmpd086 0.522 Cmpd087 0.497 Cmpd088 1.838 Cmpd091 0.057 Cmpd092 0.047 Cmpd093 0.326 Cmpd095 0.089 Cmpd096 0.289 Cmpd099 0.016 Cmpd100 0.130 Cmpd101 0.050 Cmpd105 0.009 Cmpd106 0.065 Cmpd110 0.030 Cmpd113 0.008 Cmpd114 0.017 Cmpd115 0.054 Cmpd116 0.007 Cmpd120 0.004 Cmpd121 0.010 Cmpd122 0.009 Cmpd126 0.007 Cmpd134 0.002 Cmpd135 0.028 Cmpd136 0.008 Cmpd137 0.007 Cmpd138 0.039 Cmpd139 0.356 Cmpd140 0.044 Cmpd141 0.012 Cmpd142 0.024 Cmpd143 0.025 Cmpd144 0.145 Cmpd145 0.015 Cmpd146 0.008 Cmpd147 0.022 Cmpd148 0.034 Cmpd151 0.013 Cmpd152 0.001 Cmpd153 0.005 Cmpd154 0.007 Cmpd155 0.002 Cmpd156 0.005 Cmpd157 0.004 Cmpd158 0.031 Cmpd159 0.095 Cmpd160 0.148 Cmpd161 0.023 Cmpd162 0.224 Cmpd165 0.032 Cmpd166 0.368 Cmpd167 10.000 Cmpd168 0.198 Cmpd169 0.034 Cmpd171 0.248 Cmpd172 0.166 Cmpd173 0.438 Cmpd190 0.215 Cmpd191 0.109 Cmp d192 0.164 Cmpd195 0.070 Cmpd196 0.008 Cmpd197 0.002 Cmpd200 0.022 Cmpd201 0.011 Cmpd202 0.011 Cmpd203 0.008 Cmpd204 0.065 Cmpd206 0.022 Cmpd207 0.406 Cmpd208 0.098 Cmpd209 0.296 Cmpd210 0.327 Cmpd213 0.360 Cmpd214 0.164 Cmpd215 0.274

Example 223; Use of TAU Expressing Cells as a Model for Neuronal Degeneration

Construction of a TAU Gene Over-Expressing Cell Line

[1276] A TAU expression plasmid was constructed by sub-cloning the cDNA encoding for human TAU-P301L protein, wherein proline at position 301 was substituted by a leucine residue, into mammalian expression vector pcDNA3.1 resulting in the plasmid pcDNA3.1-TAUP301L. Plasmid pcDNA3.1-TAU P301L was transfected into human neuroblastoma cells (BE-M17; ATCC No. CRL2267) using lipofectamine reagent and subsequently, independent clonal cell lines with the plasmids stably integrated into the genome were selected by antibiotic resistance selection (Geneticin (G418)), resulting in cell line M17_3 TAUP301L. Expression of the TAUP301L gene in the M17_3 TAUP301L cells was confirmed by Western blot analysis.

Use of TAU Expressing Cells as a Model of Neuronal Degeneration

[1277] M17_3TAU(P301L) cells were treated chronically with retinoic acid (RA) in low serum conditions to induce Alzheimer's disease-like intracellular signaling deregulation leading to increased TAU levels and subsequent cell death. Cytotoxicity of cells was measured by quantification of lactate dehydrogenase (LDH) levels. In dead cells LDH leaked out of the cells into the medium due to a loss of plasma-membrane integrity.

Experimental Procedure:

[1278] 3 days preceding the experiment, a pre-culture of M17_3 TAU(P301L) cells was prepared, starting from a stock culture, at a density of 50.000-100.000 cells/cm.sup.2 in culture medium (Optimem Reduced Serum with phenol red (Invitrogen, Cat. 31985-047)) supplemented with 10% fetal calf serum (FCS), 1 mM sodium pyruvate, 1 non-essential amino acids (NEAA), 500 g/ml G418 and 0.5 (ABAM). At the day of the experiment these precultures were diluted to 0, 1.10.sup.6 cells/ml in detection medium (Optimem Reduced Serum without phenol red (Gibco, Cat.11058-021) supplemented with 1% fetal calf serum (FCS), 1 mM sodium pyruvate, 1 non-essential amino acids (NEAA), 500 g/ml G418 and 0,5ABAM) and 60 L of this suspension was dispensed per well into a 96-well microtiter plate. After 3 hours of incubation at 37 C./5% CO.sub.2 an equal volume of detection medium (without FCS) containing 3.75 M RA was added and subsequently incubated for 7 days at 37 C./5% CO.sub.2. Then LDH activity was determined using the Promega Cytotox 96 Non-Radioactive cytotoxicity assay (Cat. G1780), according to the manufacturer's instructions. Cytotoxicity was defined as the ratio of LDH relative the total LDH in the cells and supernatant.

Use of the Neuroblastoma Tauopathy Model to Screen Compounds

[1279] The assay described above using the M17_3TAU(P301L) cell line allowed to screen compounds for their ability to decrease cytotoxicity in RA-challenged cells. Compounds of the invention were tested for their ability to decrease toxicity at different concentrations, ranging from low non-effective concentrations to high potent concentrations. Afterwards, the dose-dependent inhibition curve was used to calculate their EC.sub.50. A compound was considered to be active in this test when it inhibited toxicity by more than 20% relative to untreated M17_3 TAU(P301L) cells at a concentration of 10 M or lower.

[1280] The EC.sub.50 values of toxicity inhibition of the compounds of the invention using the M17_3 TAU(P301L) cells are shown in Table 13 as TAU EC.sub.50

TABLE-US-00013 TABLE 13 Compound TAU EC.sub.50 (M) Cmpd001 0.027 Cmpd002 0.008 Cmpd003 0.012 Cmpd004 0.036 Cmpd005 0.041 Cmpd006 0.008 Cmpd007 0.352 Cmpd008 0.182 Cmpd009 0.039 Cmpd010 0.306 Cmpd019 0.112 Cmpd020 0.010 Cmpd021 0.005 Cmpd022 0.035 Cmpd023 0.018 Cmpd024 0.119 Cmpd025 0.014 Cmpd026 0.088 Cmpd027 0.074 Cmpd028 0.048 Cmpd029 0.097 Cmpd030 0.013 Cmpd031 0.031 Cmpd032 0.008 Cmpd034 0.002 Cmpd035 0.024 Cmpd036 0.022 Cmpd040 0.064 Cmpd041 0.055 Cmpd042 0.003 Cmpd047 0.063 Cmpd049 0.010 Cmpd055 0.452 Cmpd056 0.075 Cmpd058 0.177 Cmpd059 0.220 Cmpd060 0.074 Cmpd061 0.685 Cmpd062 0.002 Cmpd063 0.174 Cmpd064 0.054 Cmpd065 0.763 Cmpd066 0.145 Cmpd067 0.022 Cmpd068 0.151 Cmpd069 0.161 Cmpd071 0.133 Cmpd075 0.238 Cmpd076 0.006 Cmpd089 0.485 Cmpd090 0.037 Cmpd097 0.486 Cmpd098 0.003 Cmpd102 0.017 Cmpd103 0.010 Cmpd104 0.037 Cmpd108 0.758 Cmpd109 0.487 Cmpd111 0.237 Cmpd118 0.105 Cmpd123 0.849 Cmpd125 0.103 Cmpd127 0.059 Cmpd128 0.617 Cmpd130 0.185 Cmpd131 0.135 Cmpd133 0.030 Cmpd149 0.849 Cmpd150 0.199 Cmpd163 0.418 Cmpd164 0.306 Cmpd170 0.640 Cmpd174 0.024 Cmpd175 0.105 Cmpd176 0.169 Cmpd177 0.172 Cmpd179 0.046 Cmpd180 0.222 Cmpd181 0.584 Cmpd182 0.282 Cmpd183 0.057 Cmpd184 0.135 Cmpd185 0.071 Cmpd186 0.017 Cmpd187 0.047 Cmpd188 0.004 Cmpd189 0.003

Example 224In Vivo Evaluation of Compounds

[1281] For in vivo evaluation of compound efficacy, male BKS.Cg-+Leprdb/Leprdb/OlaHsd mice (db/db mice Harlan) were used. The db/db phenotype results from a mutation in the leptin receptor gene, leading to a splice variant (Chen, Charlat et al. 1996; Lee, Proenca et al. 1996). The development of type 2 diabetes in db/db mice is associated with reduced insulin levels due to progressive -cell failure following an initial period of hypersecretion of insulin. Since these mice develop type 2 diabetes in a manner related to pathology development in humans, and the model is accepted as in vivo model for evaluation of novel anti-diabetic treatments by the Food and Drug Administration (FDA, US), it is a highly relevant model for testing candidate drugs for efficacy.

[1282] Compounds were administered intraperitoneal (IP) or oral (PO) at a dose of maximally 50 mg/kg. Mice were subjected to metabolic analysis weekly or bi-weekly. These tests included but were not limited to determination of fasting (5 hrs) and non-fasting blood glucose levels, plasma insulin levels, % glycated hemoglobin (HbA1c) levels, glucose tolerance test and insulin sensitivity test.

[1283] Treatment with cmpd110 at 15 mg/kg IP increased weight gain (FIG. 1A). Fasted blood glucose levels were significantly lower in animals treated with cmpd110 (FIG. 1B). Plasma insulin levels remained significantly higher after 6 weeks of treatment in animals treated with cmpd110 vs vehicle-treated animals (FIG. 1C). Time indications are weeks of treatment. *p<0.05; **p<0.01; n=5-8. p values are compound vs vehicle.