SUBSTITUTED PYRIDAZINES AS SKELETAL MUSCLE MODULATORS

Abstract

Provided are compounds of Formula I:

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, X and m are as defined herein.

Also provided is a pharmaceutically acceptable composition comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof.

Also provided are methods of using a compound of Formula I, or a pharmaceutically acceptable salt thereof.

Claims

1: A compound of Formula I: ##STR01135## or a pharmaceutically acceptable salt thereof, wherein: R.sup.1 is selected from the group consisting of hydrogen, halogen, CN, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, OR.sup.a, NR.sup.bR.sup.c, C.sub.6-10 aryl, and 5-10 membered heteroaryl; R.sup.2 is selected from the group consisting of C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, 5-10 membered heteroaryl and NR.sup.bR.sup.c, wherein each of the C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, and (CH.sub.2).sub.nC.sub.6-10 aryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, and (CH.sub.2).sub.nC.sub.6-10 aryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents; or R.sup.2 is C.sub.6-10 aryl substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, and (CH.sub.2).sub.nC.sub.6-10 aryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, and (CH.sub.2).sub.nC.sub.6-10 aryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents; R.sup.3 is selected from the group consisting of hydrogen, halogen, CN, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, OR.sup.a, NR.sup.bR.sup.c, C.sub.6-10 aryl, and 5-10 membered heteroaryl; R.sup.4 is selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, and SO.sub.2R.sup.a; R.sup.5 is selected from the group consisting of hydrogen, halogen, and C.sub.1-6 haloalkyl; R.sup.6 is selected from the group consisting of halogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl; R.sup.7 is selected from the group consisting of C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, and 5-10 membered heteroaryl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, OR.sup.a, OC(O)R.sup.a, OC(O)OR.sup.a, OC(O)NR.sup.bR.sup.c, NR.sup.bR.sup.c, NR.sup.dC(O)R.sup.a, NR.sup.dC(O)OR.sup.a, NR.sup.dC(O)NR.sup.bR.sup.c, NR.sup.dC(O)C(O)NR.sup.bR.sup.c, NR.sup.dC(S)R.sup.a, NR.sup.dC(S)OR.sup.a, NR.sup.dC(S)NR.sup.bR.sup.c, NR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, NR.sup.dS(O)R.sup.a, NR.sup.dSO.sub.2R.sup.a, NR.sup.dSO.sub.2NR.sup.bR.sup.c, C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, C(S)R.sup.a, C(S)OR.sup.a, C(S)NR.sup.bR.sup.c, C(NR.sup.e)NR.sup.bR.sup.c, SR.sup.a, S(O)R.sup.a, SO.sub.2R.sup.a, SO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents; R.sup.8 and R.sup.9, at each occurrence, are each independently selected from the group consisting of hydrogen, halogen, and C.sub.1-6 alkyl; X is selected from the group consisting of a bond, (CH.sub.2).sub.p, (CH.sub.2).sub.pC(O)(CH.sub.2).sub.q, (CH.sub.2).sub.pO(CH.sub.2).sub.q, (CH.sub.2).sub.pS(CH.sub.2).sub.q, (CH.sub.2).sub.pNR.sup.d(CH.sub.2).sub.q, (CH.sub.2).sub.pC(O)O(CH.sub.2).sub.q, (CH.sub.2).sub.pOC(O)(CH.sub.2).sub.q, (CH.sub.2).sub.pNR.sup.dC(O)(CH.sub.2).sub.q, (CH.sub.2).sub.pC(O)NR.sup.d(CH.sub.2).sub.q, (CH.sub.2).sub.pNR.sup.dC(O)NR.sup.d(CH.sub.2).sub.q, (CH.sub.2).sub.pNR.sup.dSO.sub.2(CH.sub.2).sub.q, and (CH.sub.2).sub.pSO.sub.2NR.sup.d(CH.sub.2).sub.q; or alternatively, X, R.sup.2 and R.sup.3, together with the carbon atoms to which they are bound, form a 5-6 membered ring optionally containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, and optionally containing one or more double bonds, and optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents; R.sup.a, at each occurrence, is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents; R.sup.b and R.sup.c, at each occurrence, are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, 5-10 membered heteroaryl, C(O)R.sup.g, C(O)OR.sup.g, C(O)NR.sup.iR.sup.j, and SO.sub.2R.sup.g, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents; R.sup.d, at each occurrence, is independently selected from the group consisting of hydrogen and C.sub.1-6 alkyl; R.sup.e, at each occurrence, is independently selected from the group consisting of hydrogen, CN, OH, C.sub.1-6 alkoxy, C.sub.1-6 alkyl and C.sub.1-6 haloalkyl; R.sup.f, at each occurrence, is independently selected from the group consisting of halogen, CN, OR.sup.h, OC(O)R.sup.h, OC(O)OR.sup.h, OC(O)NR.sup.iR.sup.j, NR.sup.iR.sup.j, NR.sup.dC(O)R.sup.h, NR.sup.dC(O)OR.sup.h, NR.sup.dC(O)NR.sup.iR.sup.j, NR.sup.dC(O)C(O)NR.sup.iR.sup.j, NR.sup.dC(S)R.sup.h, NR.sup.dC(S)OR.sup.h, NR.sup.dC(S)NR.sup.iR.sup.j, NR.sup.dC(NR.sup.e)NR.sup.iR.sup.j, NR.sup.dS(O)R.sup.h, NR.sup.dSO.sub.2R.sup.h, NR.sup.dSO.sub.2NR.sup.iR.sup.j, C(O)R.sup.h, C(O)OR.sup.h, C(O)NR.sup.iR.sup.j, C(S)R.sup.h, C(S)OR.sup.h, C(S)NR.sup.iR.sup.j, C(NR.sup.e)NR.sup.iR.sup.j, SR.sup.h, S(O)R.sup.h, SO.sub.2R.sup.h, SO.sub.2NR.sup.iR.sup.j, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.k substituents; or two R.sup.f substituents bound to a single carbon atom, together with the carbon atom to which they are both bound, form a group selected from the group consisting of carbonyl, C.sub.3-8 cycloalkyl and 3-8 membered heterocycloalkyl; R.sup.g, at each occurrence, is independently selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, phenyl, naphthyl, and C.sub.7-11 aralkyl, each optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, OH, C.sub.1-6 alkoxy, C.sub.1-6 alkyl and C.sub.1-6 haloalkyl; R.sup.h, at each occurrence, is independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.k substituents; R.sup.i and R.sup.j, at each occurrence, are each independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, 5-10 membered heteroaryl, C(O)R.sup.g, and C(O)OR.sup.g, wherein each of the C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, OH, C.sub.1-6 alkoxy, C.sub.1-6 alkyl and C.sub.1-6 haloalkyl; R.sup.k, at each occurrence, is independently selected from the group consisting of halogen, CN, OH, C.sub.1-6 alkoxy, NH.sub.2, NH(C.sub.1-6 alkyl), N(C.sub.1-6 alkyl).sub.2, NHC(O)C.sub.1-6 alkyl, NHC(O)C.sub.7-11 aralkyl, NHC(O)OC.sub.1-6 alkyl, NHC(O)OC.sub.7-11 aralkyl, OC(O)C.sub.1-6 alkyl, OC(O)C.sub.7-11 aralkyl, OC(O)OC.sub.1-6 alkyl, OC(O)OC.sub.7-11 aralkyl, C(O)C.sub.1-6 alkyl, C(O)C.sub.7-11 aralkyl, C(O)OC.sub.1-6 alkyl, C(O)OC.sub.7-11 aralkyl, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, and C.sub.2-6 alkynyl, wherein each C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, and C.sub.7-11 aralkyl substituent is optionally substituted with 1, 2 or 3 substituents selected from the group consisting of OH, C.sub.1-6 alkoxy, NH.sub.2, NH(C.sub.1-6 alkyl), N(C.sub.1-6 alkyl).sub.2, NHC(O)C.sub.1-6 alkyl, NHC(O)C.sub.7-11 aralkyl, NHC(O)OC.sub.1-6 alkyl, and NHC(O)OC.sub.7-11 aralkyl; or two R.sup.k substituents bound to a single carbon atom, together with the carbon atom to which they are both bound, form a carbonyl group; m is 0, 1 or 2; n, at each occurrence, independently is 0, 1 or 2; p is 0, 1 or 2; and q is 0, 1 or 2; provided the compound is not 6-(4-chlorophenyl)-5-methyl-N-(2-methyl-2-(piperidin-1-yl)propyl)pyridazin-3-amine, N-(2-methyl-2-(piperidin-1-yl)propyl)-6-phenyl-5-propylpyridazin-3-amine or N-(2-methyl-2-morpholinopropyl)-6-phenyl-5-propylpyridazin-3-amine.

2: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 0.

3: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein m is 1.

4: The compound of claim 3, or a pharmaceutically acceptable salt thereof, wherein R.sup.8 and R.sup.9 are each hydrogen.

5-17. (canceled)

18: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.7 is phenyl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, OR.sup.a, OC(O)R.sup.a, OC(O)OR.sup.a, OC(O)NR.sup.bR.sup.c, NR.sup.bR.sup.c, NR.sup.dC(O)R.sup.a, NR.sup.dC(O)OR.sup.a, NR.sup.dC(O)NR.sup.bR.sup.c, NR.sup.dC(O)C(O)NR.sup.bR.sup.c, NR.sup.dC(S)R.sup.a, NR.sup.dC(S)OR.sup.a, NR.sup.dC(S)NR.sup.bR.sup.c, NR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, NR.sup.dS(O)R.sup.a, NR.sup.dSO.sub.2R.sup.a, NR.sup.dSO.sub.2NR.sup.bR.sup.c, C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, C(S)R.sup.a, C(S)OR.sup.a, C(S)NR.sup.bR.sup.c, C(NR.sup.e)NR.sup.bR.sup.c, SR.sup.a, S(O)R.sup.a, SO.sub.2R.sup.a, SO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

19: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.7 is 5-10 membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, OR.sup.a, OC(O)R.sup.a, OC(O)OR.sup.a, OC(O)NR.sup.bR.sup.c, NR.sup.bR.sup.c, NR.sup.dC(O)R.sup.a, NR.sup.dC(O)OR.sup.a, NR.sup.dC(O)NR.sup.bR.sup.c, NR.sup.dC(O)C(O)NR.sup.bR.sup.c, NR.sup.dC(S)R.sup.a, NR.sup.dC(S)OR.sup.a, NR.sup.dC(S)NR.sup.bR.sup.c, NR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, NR.sup.dS(O)R.sup.a, NR.sup.dSO.sub.2R.sup.a, NR.sup.dSO.sub.2NR.sup.bR.sup.c, C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, C(S)R.sup.a, C(S)OR.sup.a, C(S)NR.sup.bR.sup.c, C(NR.sup.e)NR.sup.bR.sup.c, SR.sup.a, S(O)R.sup.a, SO.sub.2R.sup.a, SO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

20: The compound of claim 19, or a pharmaceutically acceptable salt thereof, wherein R.sup.7 is pyridyl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, OR.sup.a, OC(O)R.sup.a, OC(O)OR.sup.a, OC(O)NR.sup.bR.sup.c, NR.sup.bR.sup.c, NR.sup.dC(O)R.sup.a, NR.sup.dC(O)OR.sup.a, NR.sup.dC(O)NR.sup.bR.sup.c, NR.sup.dC(O)C(O)NR.sup.bR.sup.c, NR.sup.dC(S)R.sup.a, NR.sup.dC(S)OR.sup.a, NR.sup.dC(S)NR.sup.bR.sup.c, NR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, NR.sup.dS(O)R.sup.a, NR.sup.dSO.sub.2R.sup.a, NR.sup.dSO.sub.2NR.sup.bR.sup.c, C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, C(S)R.sup.a, C(S)OR.sup.a, C(S)NR.sup.bR.sup.c, C(NR.sup.e)NR.sup.bR.sup.c, SR.sup.a, S(O)R.sup.a, SO.sub.2R.sup.a, SO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, 3-6 membered heterocycloalkyl, 3-6 membered heterocycloalkenyl, phenyl, naphthyl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

21: The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein R.sup.7 is 2-pyridyl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, OR.sup.a, OC(O)R.sup.a, OC(O)OR.sup.a, OC(O)NR.sup.bR.sup.c, NR.sup.bR.sup.c, NR.sup.dC(O)R.sup.a, NR.sup.dC(O)OR.sup.a, NR.sup.dC(O)NR.sup.bR.sup.c, NR.sup.dC(O)C(O)NR.sup.bR.sup.c, NR.sup.dC(S)R.sup.a, NR.sup.dC(S)OR.sup.a, NR.sup.dC(S)NR.sup.bR.sup.c, NR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, NR.sup.dS(O)R.sup.a, NR.sup.dSO.sub.2R.sup.a, NR.sup.dSO.sub.2NR.sup.bR.sup.c, C(O)R.sup.a, C(O)OR.sup.a, C(O)NR.sup.bR.sup.c, C(S)R.sup.a, C(S)OR.sup.a, C(S)NR.sup.bR.sup.c, C(NR.sup.e)NR.sup.bR.sup.c, SR.sup.a, S(O)R.sup.a, SO.sub.2R.sup.a, SO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, 3-6 membered heterocycloalkyl, 3-6 membered heterocycloalkenyl, phenyl, naphthyl, C.sub.7-11 aralkyl, and 5-10 membered heteroaryl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloalkenyl, 3-8 membered heterocycloalkyl, 3-8 membered heterocycloalkenyl, C.sub.6-10 aryl, C.sub.7-11 aralkyl and 5-10 membered heteroaryl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

22: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein X is a bond.

23. (canceled)

24: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is phenyl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, or (CH.sub.2).sub.nnaphthyl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

25: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is 5-10 membered heteroaryl optionally substituted with 1, 2, 3, 4 or 5 substituents selected from the group consisting of halogen, CN, oxo, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, or (CH.sub.2).sub.nnaphthyl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

26: The compound of claim 25, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is selected from the group consisting of pyridyl, pyrimidyl, pyrazyl, pyridazyl, triazyl, furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl and tetrazolyl, each optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of halogen, CN, oxo, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, or (CH.sub.2).sub.nnaphthyl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

27: The compound of claim 26, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is selected from the group consisting of pyridyl, pyrimidyl, pyrazyl, pyridazyl, triazyl, furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl and tetrazolyl, wherein each of the pyridyl, pyrimidyl, pyrazyl, pyridazyl, triazyl, furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl or tetrazolyl is substituted with a substituent selected from the group consisting of (CH.sub.2).sub.nC(O)OR.sup.a and (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c; and optionally substituted with 1, 2 or 3 additional substituents selected from the group consisting of halogen, CN, oxo, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, or (CH.sub.2).sub.nnaphthyl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

28: The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is selected from the group consisting of furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl and tetrazolyl, each substituted with (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c.

29: The compound of claim 26, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is selected from the group consisting of pyridyl, pyrimidyl, pyrazyl, pyridazyl, triazyl, furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl and tetrazolyl, wherein each of the pyridyl, pyrimidyl, pyrazyl, pyridazyl, triazyl, furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl or tetrazolyl is substituted with (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, wherein R.sup.a is C.sub.1-6 alkyl or 3-8 membered heterocycloalkyl, each optionally substituted with 1, 2 or 3 additional substituents selected from the group consisting of halogen, CN, oxo, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, or (CH.sub.2).sub.nnaphthyl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

30: The compound of claim 29, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is selected from the group consisting of furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl and tetrazolyl, wherein each of the furanyl, pyrrolyl, thiophenyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, imidazolyl, triazolyl or tetrazolyl is substituted with (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, wherein R.sup.a is selected from the group consisting of C.sub.1-6 alkyl, C.sub.1-6 alkyl-OH and C.sub.1-6 alkyl-NH.sub.2, each optionally substituted with 1, 2 or 3 additional substituents selected from the group consisting of halogen, CN, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl.

31: The compound of claim 25, or a pharmaceutically acceptable salt thereof, wherein R.sup.2 is selected from the group consisting of indolyl, indazolyl, benzimidazolyl, benzoxazolyl and benzoisoxazolyl, each optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of halogen, CN, oxo, (CH.sub.2).sub.nOR.sup.a, (CH.sub.2).sub.nOC(O)R.sup.a, (CH.sub.2).sub.nOC(O)OR.sup.a, (CH.sub.2).sub.nOC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(O)C(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(S)R.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)OR.sup.a, (CH.sub.2).sub.nNR.sup.dC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nNR.sup.dS(O)R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2R.sup.a, (CH.sub.2).sub.nNR.sup.dSO.sub.2NR.sup.bR.sup.c, (CH.sub.2).sub.nC(O)R.sup.a, (CH.sub.2).sub.nC(O)OR.sup.a, (CH.sub.2).sub.nC(O)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(S)R.sup.a, (CH.sub.2).sub.nC(S)OR.sup.a, (CH.sub.2).sub.nC(S)NR.sup.bR.sup.c, (CH.sub.2).sub.nC(NR.sup.e)NR.sup.bR.sup.c, (CH.sub.2).sub.nSR.sup.a, (CH.sub.2).sub.nS(O)R.sup.a, (CH.sub.2).sub.nSO.sub.2R.sup.a, (CH.sub.2).sub.nSO.sub.2NR.sup.bR.sup.c, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, and (CH.sub.2).sub.nnaphthyl, wherein each of the C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, (CH.sub.2).sub.nC.sub.3-8 cycloalkyl, (CH.sub.2).sub.n3-8 membered heterocycloalkyl, (CH.sub.2).sub.nphenyl, or (CH.sub.2).sub.nnaphthyl groups is optionally substituted with 1, 2, 3, 4 or 5 R.sup.f substituents.

32: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is selected from the group consisting of hydrogen, halogen, CN, CF.sub.3 and methyl.

33: The compound of claim 32, or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is hydrogen.

34: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.3 is selected from the group consisting of hydrogen, halogen, CN, CF.sub.3 and methyl.

35: The compound of claim 34, or a pharmaceutically acceptable salt thereof, wherein R.sup.3 is hydrogen.

36: The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R.sup.4 is hydrogen.

37: A compound selected from the group consisting of ##STR01136## ##STR01137## ##STR01138## or a pharmaceutically acceptable salt thereof.

38: A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof.

39: The pharmaceutical composition of claim 38, wherein the pharmaceutical composition is formulated for oral, sublingual, subcutaneous, parenteral, intravenous, intranasal, topical, transdermal, intraperitoneal, intramuscular, intrapulmonary, vaginal, rectal, or intraocular administration.

40: The pharmaceutical composition of claim 39, wherein the pharmaceutical composition is formulated for oral administration.

41: A method for the treatment of a disease or condition selected from the group consisting of neuromuscular disorders, conditions of muscle wasting, muscular myopathies, rehabilitation-related deficits, peripheral vascular disease, peripheral arterial disease, frailty, muscle atrophy and fatigue, metabolic syndrome, chronic fatigue syndrome, heart failure, chronic obstructive pulmonary disease (COPD), and obesity; the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

42: A method for the treatment of a disease selected from the group consisting of Amyotrophic Lateral Sclerosis (ALS), Spinal Muscular Atrophy (SMA) and myasthenia gravis; the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

43: A method for the treatment of a disease selected from the group consisting of peripheral vascular disease and peripheral arterial disease; the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

Description

EXAMPLE 1: PREPARATION OF N-(5-(6-(2-(4-FLUOROPHENYL)-2-METHYLPROPYLAMINO)PYRIDAZIN-3-YL)-1H-INDAZOL-3-YL)ACETAMIDE

[0239] ##STR00021##

6-Chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine

[0240] A solution of (2-(4-fluorophenyl)-2-methylpropan-1-amine (27 g, 160 mmol, 1.6 equiv), 3,6-dichloropyridazine (15 g, 100 mmol, 1.0 equiv) and K.sub.2CO.sub.3 (42 g, 302 mmol, 3.0 equiv) in isopropanol (15 mL) was stirred at 100 C. for 36 hours. The cooled mixture was partitioned between water and EtOAc and the organic fraction was dried over Na.sub.2SO.sub.4 and concentrated in vacuo. Partial purification over silica gel using a 30-75% gradient of EtOAc/hexanes gave the desired product (29.6 g, 103%) which was used without further purification.

##STR00022##

2-Fluoro-5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)benzonitrile

[0241] To a solution of 6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine (5.0 g, 23 mmol, 1.0 equiv) and K.sub.2CO.sub.3 (9.4 g, 68 mmol, 3.0 equiv) in dioxane (35 mL) was added Pd(dppf)Cl.sub.2 (1.7 g, 2.3 mmol, 0.1 equiv) and 3-cyano-4-fluorophenylboronic acid (5.0 g, 30 mmol, 1.3 equiv). The mixture was stirred at 80 C. for 3 hours after which it was allowed to cool to room temperature and concentrated in vacuo. The residue was diluted with EtOAc, washed with saturated NaHCO.sub.3, dried over Na.sub.2SO.sub.4 and evaporated to dryness. The residue was purified by reverse phase HPLC using a CH.sub.3CN/water gradient to give the desired product (5.3 g, 63%).

##STR00023##

5-(6-(2-(4-Fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1H-indazol-3-amine

[0242] To a solution of 2-fluoro-5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)benzonitrile (0.53 g, 1.5 mmol, 1.0 equiv) in n-butanol (10 mL) was added hydrazine monohydrate (1.0 mL, 32 mmol, 20 equiv). The mixture was stirred at 110 C. for two hours followed by evaporation of the solvents in vacuo. Purification on a preparatory TLC plate using 5% MeOH/DCM as eluent gave the desired product (195 mg, 36%), m/z=377.1 [M+H].

##STR00024##

N-(5-(6-(2-(4-Fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1H-indazol-3-yl)acetamide

[0243] To a solution of 5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1H-indazol-3-amine (50 mg, 133 mol) in pyridine (1 mL) was added acetyl chloride (9.5 L, 133 mol). The mixture was stirred for 15 min, concentrated, purified by reverse phase chromatography using a CH.sub.3CN/water gradient to afford 25 mg of white solid, m/z=419.9 [M+H].

EXAMPLE 2: PREPARATION OF N-(2-(4-FLUOROPHENYL)-2-METHYLPROPYL)-6-(1H-PYRAZOL-1-YL)PYRIDAZIN-3-AMINE

[0244] ##STR00025##

[0245] Step 1:

[0246] To a solution of pyrazole (3.69 g, 25 mmol, 1.0 equiv) in NMP (25 mL) was added sodium hydride (60% dispersion in mineral oil, 1.5 g, 38 mmol, 1.5 equiv). The mixture was stirred for 15 min, followed by the addition of 3,6-dichloropyridazine (3.02 g, 25 mmol, 1.0 equiv). The reaction mixture was stirred for 1.5 h and then diluted with water (50 mL) and ethyl acetate (100 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (350 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give 3.89 g of 3-chloro-6-(1H-pyrazol-1-yl)pyridazine as a crude tan solid that was used directly in the next step.

[0247] Step 2:

[0248] To a 5 mL microwave vial was added 3-chloro-6-(1H-pyrazol-1-yl)pyridazine (320 mg, 1.8 mmol, 1.0 equiv), 2-(4-fluorophenyl)-2-methylpropan-1-amine (386 mg, 2.3 mmol, 1.3 equiv), diisopropylethylamine (620 L, 3.6 mmol, 2.0 equiv), and NMP (4 mL). The reaction was heated in a microwave reactor to 250 C. and stirred for 15 min. A portion (roughly a third) of the reaction was purified by reverse phase chromatography and then silica gel chromatography (10% MeOH/DCM) to give 61 mg of N-(2-(4-fluorophenyl)-2-methylpropyl)-6-(1H-pyrazol-1-yl)pyridazin-3-amine, m/z=312.1 [M+H].

EXAMPLE 3: PREPARATION OF 5-(6-(2-(4-FLUOROPHENYL)-2-METHYLPROPYLAMINO) PYRIDAZIN-3-YL)-1,3,4-OXADIAZOL-2(3H)-ONE

[0249] ##STR00026##

Methyl 6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-3-carboxylate

[0250] To a 25 mL round bottom flask was added methyl 6-chloropyridazine-3-carboxylate (0.50 g, 2.90 mmol, 1.0 equiv), 2-(4-fluorophenyl)-2-methylpropan-1-amine (0.60 g, 3.6 mmol, 1.2 equiv), potassium carbonate (300 mg, 2.2 mmol, 0.75 equiv), and isopropanol (3 mL). The reaction mixture was stirred and heated at 120 C. for 12 h. The reaction was then filtered through celite, concentrated, and purified by silica gel chromatography (0-40% EtOAC/hexanes) to afford 360 mg (43%) of methyl 6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-3-carboxylate as an off-white foam.

##STR00027##

5-(6-(2-(4-Fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1,3,4-oxadiazol-2(3H)-one

[0251] To a 25 mL round bottom flask was added methyl 6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-3-carboxylate (100 mg, 0.3 mmol, 1.0 equiv), hydrazine hydrate (1 mL), and ethanol (5 mL)). The reaction was refluxed for 2 h and concentrated. N,N-Carbonyldiimidazole (100 mg, 0.6 mmol, 2.0 equiv) and DMF (1 mL) were then added to the crude product and the reaction was heated to 90 C. for 1.5 h. The reaction mixture was directly purified by reverse phase column chromatography to afford 72 mg (67%) of 5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1,3,4-oxadiazol-2(3H)-one as a white solid, m/z=330.0 [M+H].

EXAMPLE 4: PREPARATION OF 6-(2-AMINO-1H-IMIDAZOL-4-YL)-N-(2-(4-FLUOROPHENYL)-2-METHYLPROPYL)PYRIDAZIN-3-AMINE

[0252] ##STR00028##

2-Bromo-1-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)ethanone

[0253] 6-chloro-N-(2-(4-fluorophenyl)-2-methyl propyl)pyridazin-3-amine (300 mg, 1.1 mmol, 1.0 equiv) and dioxane (5 mL) were added to a microwave vial and sonication was applied until the mixture was homogeneous. Tributyl(1-ethoxyvinyl)stannane (475 L, 1.4 mmol, 1.3 equiv) and trans-dichlorobis(triphenylphosphine)palladium (30 mg, 0.04 mmol, 0.03 equiv) were then added, and the reaction was heated in a microwave reactor at 150 C. for 20 min. The reaction was concentrated, dissolved in EtOAc (25 mL), and mixed with 2.0M potassium fluoride (5 mL). The mixture was filtered through celite, and then washed with water, dried over Na.sub.2SO.sub.4, filtered, and concentrated. The crude solid was redissolved in 50% THF/water (4 mL), followed by the addition of NBS (300 mg, 1.7 mmol, 1.5 equiv). The reaction mixture was stirred for 1 h and then diluted with brine (20 mL) and ethyl acetate (20 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer. The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a brown oil that was purified by silica gel chromatography (0-100% EtOAC/hexanes) to afford 270 mg of 2-bromo-1-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)ethanone as an orange oil.

##STR00029##

N-(4-(6-(2-(4-Fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1H-imidazol-2-yl)acetamide

[0254] To a 3 mL microwave reaction vial was added 2-bromo-1-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)ethanone (125 mg, 0.3 mmol, 1.0 equiv), acetyl guanidine (90 mg, 0.6 mmol, 2.0 equiv) and acetonitrile (2 mL). The reaction was heated in a microwave reactor at 100 C. for 13 min. The reaction was filtered and directly purified by reverse phase column chromatography to afford N-(4-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1H-imidazol-2-yl)acetamide (70 mg) as an white solid. m/z=369.2 [M+H]+.

##STR00030##

6-(2-Amino-1H-imidazol-4-yl)-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine

[0255] To a 10 mL round bottom flask was added N-(4-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)-1H-imidazol-2-yl)acetamide (22 mg, 59 mol), concentrated HCl (100 L) and methanol (1 mL). The reaction was refluxed for 12 h and then concentrated, redissolved in EtOAc (10 mL), washed with saturated sodium carbonate (210 mL) and brine (110 mL), dried (Na.sub.2SO.sub.4) and concentrated to yield 8 mg (42%) of 6-(2-amino-1H-imidazol-4-yl)-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine as a pale yellow solid, m/z=327.2 [M+H].

EXAMPLE 5: PREPARATION OF 6-(5-AMINO-1H-PYRAZOL-3-YL)-N-(2-(4-FLUOROPHENYL)-2-METHYLPROPYL)PYRIDAZIN-3-AMINE

[0256] ##STR00031##

[0257] To a 20 dram vial was added 2-bromo-1-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)ethanone (13 mg, 35 mol, 1.0 equiv), sodium cyanide (25 mg, 500 mol, 15.0 equiv) and ethanol (1 mL). The reaction mixture was heated to 60 C. for 30 min. After cooling to room temperature, the reaction was filtered. Hydrazine hydrate (250 L) was then added, and the reaction mixture was heated to 100 C. for 2 h. The reaction was filtered and directly purified by reverse phase column chromatography to afford 6-(5-amino-1H-pyrazol-3-yl)-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine (2 mg) as an white solid, m/z=327.2 [M+H].

EXAMPLE 6: PREPARATION OF 6-ETHYL-N-(2-(4-FLUOROPHENYL)-2-METHYLPROPYL) PYRIDAZIN-3-AMINE

[0258] ##STR00032##

[0259] Step 1:

[0260] To a 5 mL microwave reaction vial was added 6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine (123 mg, 441 mol, 1.0 equiv), 2,4,6-trivinyl-1,3,5,2,4,6-trioxatriborinane (159 mg, 661 mol, 1.5 equiv), Cl.sub.2Pd(dppf) (54 mg, 66 mol, 0.15 equiv), potassium carbonate (182 mg, 1.32 mmol, 3 equiv), and dioxane (21 mL). The reaction was heated in a microwave reactor at 140 C. for 12 min and then diluted with water (20 mL) and ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (120 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (20-50% EtOAc/hexanes) to give 50 mg (46%) of N-(2-(4-fluorophenyl)-2-methylpropyl)-6-vinylpyridazin-3-amine as a white solid.

[0261] Step 2:

[0262] The isolated product from Step 1 was dissolved in ethanol (10 mL) and transferred to a 20 dram vial. Palladium (10% on carbon, 10 mg) was then added, and the reaction was stirred under 60 psi of hydrogen for 3 days. The reaction was then filtered, concentrated, and purified by reverse phase column chromatography to afford 3 mg (10%) of 6-ethyl-N-(2-(4-fluorophenyl)-2-methylpropyl) pyridazin-3-amine as a clear oil, m/z=274 [M+H].

EXAMPLE 7: PREPARATION OF 2-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)PROPAN-2-OL

[0263] ##STR00033##

Methyl 6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carboxylate

[0264] To a 20 dram vial was added methyl 6-chloropyridazine-3-carboxylate (510 mg, 2.7 mmol, 1.0 equiv), (1-(3-fluoropyridin-2-yl)cyclobutyl)methanamine (738 mg, 4 mmol, 1.5 equiv), DIPEA (0.7 mL, 4 mmol, 1.5 equiv), and NMP (2 mL). The reaction was heated at 120 C. for 40 min and then diluted with water (20 mL) and ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (120 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (20-100% EtOAc/hexanes) to give 440 mg (48%) of methyl 6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carboxylate as a white solid. m/z=331.1 [M+H]+.

##STR00034##

2-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)propan-2-ol

[0265] A portion of the isolated methyl 6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carboxylate (99 mg, 0.3 mmol, 1.0 equiv) was dissolved in THF (10 mL) and transferred to a 20 dram vial. The mixture was cooled to 0 C. and MeMgBr (3M in Et.sub.2O, 0.5 mL, 1.5 mmol, 5 equiv) was added. The reaction was allowed to warm to rt and then stirred for 15 min. The reaction mixture was poured into a mixture of EtOAc (30 mL) and saturated ammonium chloride (15 mL). The organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (0-20% MeOH/CH.sub.2Cl.sub.2) to give 42 mg (43%) of 2-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)propan-2-ol as a white powder. m/z=317 [M+H]+.

EXAMPLE 8: PREPARATION OF 1-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)ETHANONE

[0266] ##STR00035##

6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carbonitrile

[0267] To a 20 dram vial was added 6-chloropyridazine-3-carbonitrile (1.0 g, 7.2 mmol, 1.0 equiv), (1-(3-fluoropyridin-2-yl)cyclobutyl)methanamine (1.36 g, 7.6 mmol, 1.05 equiv), triethylamine (2.1 mL, 14.4 mmol, 2.0 equiv), and NMP (2 mL). The reaction was heated at 130 C. for 12 h and then diluted with water (20 mL) and ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (120 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (20-30% EtOAc/hexanes) to give 507 mg (25%) of 6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carbonitrile. m/z=284 [M+H]+.

##STR00036##

1-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)ethanone

[0268] 6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carbonitrile (500 mg, 1.8 mmol, 1.0 equiv) was dissolved in THF (4.5 mL) and transferred to a 20 dram vial. The mixture was cooled to 0 C. and MeMgBr (1.8 mL, 5.3 mmol of a 3M solution in Et.sub.2O, 2.9 equiv) was added. The reaction was stirred at this temperature for 15 min. The reaction mixture was poured into ice water, acidified to pH of 2 with 2N aqueous hydrochloric acid, and then extracted EtOAc (30 mL). The organic layer was then separated, dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (50% EtOAc/hexanes) to give 104 mg (18%) of 1-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)ethanone as a white powder. m/z=301.1 [M+H]+.

EXAMPLE 9: PREPARATION OF N-(2-(4-FLUOROPHENYL)-2-METHYLPROPYL)-6-(PYRIDIN-2-YL)PYRIDAZIN-3-AMINE

[0269] ##STR00037##

[0270] To a 25 mL round bottom flask was added 2-bromopyridine (500 mg, 3.2 mmol, 1.0 equiv), triisopropylborate (654 mg, 3.5 mmol, 1.1 equiv), and an 80% toluene/THF mixture (16 mL). The mixture was cooled to 78 C. After stirring for 10 min, n-BuLi (1.7 mL, 3.48 mmol, 1.1 equiv of a 2.0M/hexanes solution) was slowly added over an hour. After the addition was complete, the reaction mixture was stirred for 30 min and allowed to warm to rt and stirred overnight. The reaction was then concentrated at 100 C. and dried in vacuo for 2 h. To 100 mg of this crude solid in a microwave vial was added 6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine (70 mg, 0.25 mmol), Pd.sub.2dba.sub.3 (10 mg, 0.011 mmol), PO(tBu).sub.3 (5 mg, 0.030 mmol), potassium fluoride (43 mg, 0.75 mmol), and dioxane (0.75 mL). The reaction was degassed with nitrogen for 5 minutes and then heated in a microwave reactor at 160 C. for 15 min. The reaction was then concentrated, dissolved in EtOAc (25 mL), washed with water, dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by reverse phase column chromatography to give 5 mg of N-(2-(4-fluorophenyl)-2-methylpropyl)-6-(pyridin-2-yl)pyridazin-3-amine as a white solid. m/z=323.1 [M+H]+.

EXAMPLE 10: PREPARATION OF 6-(6-(2-(4-FLUOROPHENYL)-2-METHYLPROPYLAMINO)PYRIDAZIN-3-YL)NICOTINAMIDE

[0271] ##STR00038##

[0272] To a 20 dram vial was added 2-bromo-5-cyanopyridine (182 mg, 1.0 mmol, 1.0 equiv), hexamethylditin (639 mg, 1.1 mmol, 1.1 equiv), Cl.sub.2Pd(Ph.sub.3P).sub.2 (91 mg, 0.13 mmol, 0.13 equiv), triphenylarsine (34 mg, 0.11 mmol, 0.11 equiv), and dioxane (7 mL). The reaction mixture was stirred and heated to 80 C. for 12 h. The reaction was then concentrated, followed by the addition of tert-butyl 6-bromopyridazin-3-yl(2-(4-fluorophenyl)-2-methylpropyl)carbamate (423 mg, 1.0 mmol, 1.0 equiv), Pd(Ph.sub.3P).sub.4 (172 mg, 0.15 mmol, 0.15 equiv), and DMF (3.3 mL). The reaction was stirred and heated to 100 C. for 3 h. After cooling to room temperature, the reaction was diluted with aqueous potassium fluoride (5 mL), extracted with ethyl acetate (20 mL) and washed with brine (20 mL). The organic layer was then dried (Na.sub.2SO.sub.4), filtered, and concentrated to give crude tert-butyl 6-(5-cyanopyridin-2-yl)pyridazin-3-yl(2-(4-fluorophenyl)-2-methylpropyl)carbamate.

[0273] To a 20 dram vial was added crude tert-butyl 6-(5-cyanopyridin-2-yl)pyridazin-3-yl(2-(4-fluorophenyl)-2-methylpropyl)carbamate, hydrogen peroxide (2 mL), and potassium carbonate (150 mg). The reaction was stirred for 30 min and then diluted with water (20 mL) and ethyl acetate (50 mL).

[0274] After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (20 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was subsequently treated with 4N HCl/dioxane (1 mL). The reaction was stirred for 1 h at room temperature, concentrated, quenched with aqueous sodium bicarbonate, and extracted with ethyl acetate (20 mL). The organic layer was then dried (Na.sub.2SO.sub.4), filtered, and concentrated to give a crude solid that was purified by reverse phase column chromatography to afford 10 mg of 6-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)nicotinamide, m/z=366.1 [M+H].

EXAMPLE 11: PREPARATION OF 6-(2-AMINOPYRIDIN-3-YL)-N-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYL)PYRIDAZIN-3-AMINE

[0275] ##STR00039##

N-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methyl)-6-(2-methoxypyridin-3-yl)pyridazin-3-amine

[0276] To a 20 dram vial was added 6-chloro-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine (1.8 g, 6.23 mmol, 1.0 equiv), 2-methoxypyridin-3-ylboronic acid (1.0 g, 6.54 mmol, 1.1 equiv), Cl.sub.2Pd(dppf) (350 mg, 0.43 mmol, 0.07 equiv), 2M potassium carbonate (8 mL, 15.5 mmol, 2.5 equiv), and dioxane (21 mL). The reaction was stirred and heated to 90 C. for 2 h and then diluted with water (20 mL) and ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with lithium chloride (120 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography to give N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)-6-(2-methoxypyridin-3-yl)pyridazin-3-amine (1.7 g, 77%) as an off-white solid.

##STR00040##

6-(2-Chloropyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine

[0277] To a 50 mL round bottom flask was added N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)-6-(2-methoxypyridin-3-yl)pyridazin-3-amine (1.7 g, 4.7 mmol), concentrated hydrochloric acid (15 mL), and methanol (15 mL). The reaction was heated to 90 C. and stirred for 12 h. The reaction was concentrated, brought to pH of 11 through the addition of saturated potassium carbonate (20 mL), and then diluted with ethyl acetate (50 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and washed with lithium chloride (120 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give 3-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)pyridin-2-ol (1.6 g, 95%) as a tan powder. The isolated product (1.3 g, 3.7 mmol, 1.0 equiv) was transferred to a 100 mL round bottom flask, followed by the addition of a mixture of phosphorous oxytrichloride (24 mL) and DMF (8 mL). The reaction was heated to 90 C. and stirred for 6 h. The reaction was concentrated and carefully quenched with a 50% mixture of saturated sodium bicarbonate and lithium chloride until gas evolution ceased. The mixture was extracted with ethyl acetate (100 mL). The combined organic layers were then dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel column chromatography to give 1.2 g (88%) of 6-(2-chloropyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine as an off-white solid.

##STR00041##

6-(2-Aminopyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine

[0278] To a 5 mL microwave reaction vessel was added 6-(2-chloropyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine (750 mg, 2.0 mmol), hydrazine hydrate (1 mL), and dioxane (4 mL). The reaction was heated in a microwave reactor to 160 C. for 15 min, then diluted with ethyl acetate (50 mL), and washed with brine (20 mL). The organic layer was dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by reverse phase column chromatography to give 150 mg of N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)-6-(2-hydrazinylpyridin-3-yl)pyridazin-3-amine as an off-white solid. The isolated product was then dissolved in methanol and added to a vial containing 1 mL of Raney Nickel suspension in water. The mixture was then stirred under 50 psi of hydrogen for 2 h. The reaction was then filtered, concentrated, and purified by reverse phase column chromatography to give 10 mg (88%) of 6-(2-aminopyridin-3-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine as an off-white solid, m/z=351.1 [M+H].

EXAMPLE 12: PREPARATION OF N1-(5-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO) PYRIDAZIN-3-YL)-1H-INDAZOL-3-YL)ETHANE-1,2-DIAMINE

[0279] ##STR00042##

Benzyl 2-(2-Fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzamido)ethylcarbamate

[0280] To a 20 dram vial was added 2-fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzoic acid (320 mg, 0.8 mmol, 1.0 equiv), benzyl 2-aminoethylcarbamate (242 mg, 1.0 mmol, 1.3 equiv), HOBt (141 mg, 1.0 mmol, 1.3 equiv), EDC HCl (200 mg, 1.0 mmol, 1.3 equiv), DIPEA (550 L, 3.8 equiv) and CH.sub.2Cl.sub.2 (5 mL). The reaction was stirred for 4 h and then concentrated and then purified using a silica gel column (50%-100% EtOAc/hexanes) to afford 230 mg (50%) of benzyl 2-(2-fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzamido)ethylcarbamate as a white foam.

##STR00043##

Benzyl 2-(2-fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)phenylthioamido)ethylcarbamate

[0281] In a 20 dram vial containing benzyl 2-(2-fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzamido)ethylcarbamate (230 mg, 0.5 mmol, 1 equiv) was added Lawesson's reagent (162 mg, 0.4 mmol, 0.8 equiv) and dioxane (10 mL). The reaction was heated to 100 C. and stirred for 1 h, concentrated, and then purified using a silica gel column (35%-100% EtOAc/hexanes) to give 203 mg (86%) of benzyl 2-(2-fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)phenylthioamido)ethylcarbamate as a pale yellow oil.

##STR00044##

Benzyl 2-(5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-indazol-3-ylamino)ethylcarbamate

[0282] The isolated benzyl 2-(2-fluoro-5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)phenylthioamido)ethyl-carbamate was transferred to a 20 dram vial, followed by the addition of hydrazine hydrate (0.1 mL) and dioxane (2 mL). The reaction was heated to 100 C. and stirred for 12 h, concentrated, and then purified using a silica gel column (5%-10% MeOH/EtOAc) to yield 48 mg (25%) of benzyl 2-(5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-indazol-3-ylamino)ethylcarbamate as a pale yellow oil.

##STR00045##

N1-(5-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-indazol-3-yl)ethane-1,2-diamine

[0283] Benzyl 2-(5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-indazol-3-ylamino)ethylcarbamate (48 mg, 84 mol) was dissolved in acetonitrile (5 mL), and TMSI (0.5 mL) was added. The reaction was stirred for 15 min, diluted with methanol (15 mL), concentrated, and was directly purified by reverse phase column chromatography to yield 20 mg (88%) of N1-(5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-indazol-3-yl)ethane-1,2-diamine as a yellow solid, m/z=433 [M+H].

EXAMPLE 13: PREPARATION OF 6-(5-AMINOPYRIDIN-2-YL)-N-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYL)PYRIDAZIN-3-AMINE

[0284] ##STR00046##

2-Bromo-5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine

[0285] To a 25 mL round bottom flask was added 5-amino-2-bromopyridine (600 mg, 3.5 mmol, 1.0 equiv), hexane-2,5-dione (420 mg, 4.2 mmol, 1.2 equiv), p-toluenesulfonic acid (5 mg), and toluene (3.5 mL). A Dean-Stark trap was fitted on top of the round bottom flask and the reaction mixture was heated to reflux for 2 h. The reaction was then concentrated and purified by silica gel column chromatography (5% ethyl acetate/hexanes) to give 660 mg (76%) of 2-bromo-5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine.

##STR00047##

tert-Butyl-6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0286] THF (8.5 mL) was cooled to 78 C. under a nitrogen atmosphere. tBuLi (1.7 mL, 2.9 mmol, 2.0 equiv) was added, followed by the addition of 2-bromo-5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridine (370 mg, 1.47 mmol, 1.0 equiv dissolved in 2 mL THF) over 2 min. The reaction as stirred for 45 min at 78 C. Zinc chloride (510 mg, 3.75 mmol, 2.5 equiv dissolved in 5 mL of THF) was added and the reaction was allowed to warm to rt and stirred for 3 h. (t-Bu.sub.3P).sub.2Pd (41 mg, 0.015 mmol, 0.10 equiv dissolved in 5 mL of THF) and t-butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (393 mg, 0.1 mmol, 0.07 equiv dissolved in 5 mL of THF) were added and the reaction was refluxed for 4 h followed by dilution with sodium bicarbonate (20 mL), and extraction with ethyl acetate (40 mL). The organic layer was dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (35% EtOAc/hexanes) to give 245 mg (46%) of tert-butyl 6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate.

##STR00048##

6-(5-Aminopyridin-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine

[0287] To a 20 dram vial was added tert-butyl 6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (245 mg, 0.5 mmol) and a 5 mL of a 50% mixture of TFA and CH.sub.2Cl.sub.2. The reaction was stirred for 15 min, concentrated, and then diluted with sodium bicarbonate (20 mL) and extracted with ethyl acetate (40 mL). The organic layer was dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (60% EtOAc/hexanes) to give 91 mg (46%) of 6-(5-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine. This product was transferred to a 100 mL round bottom flask to which was added hydroxylamine hydrochloride (270 mg), triethylamine (5 mL), and ethanol (20 mL). The reaction mixture was heated to reflux overnight and then concentrated, diluted with sodium bicarbonate (20 mL) and extracted with ethyl acetate (40 mL). The organic layer was dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by reverse phase column chromatography to afford 28 mg of 6-(5-aminopyridin-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine, m/z=351.2 [M+H].

EXAMPLE 14: PREPARATION OF 3-(6-(2-(4-FLUOROPHENYL)-2-METHYLPROPYLAMINO)-4-METHYLPYRIDAZIN-3-YL)BENZAMIDE

[0288] ##STR00049##

6-Chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)-5-methylpyridazin-3-amine

[0289] A solution of (2-(4-fluorophenyl)-2-methylpropan-1-amine (5.5 g, 33 mmol, 1.8 equiv), 3,6-dichloro-4-methylpyridazine (3.0 g, 18 mmol, 1.0 equiv) and K.sub.2CO.sub.3 (5.1 g, 37 mmol, 2.0 equiv) in isopropanol (7.5 mL) was stirred at 100 C. under a blanket of nitrogen for 18 hours. The cooled mixture was partitioned between water and EtOAc and the organic fraction was concentrated in vacuo. Purification over silica gel using a 20-35% gradient of EtOAc/hexanes gave the desired product (0.80 g, 15%) of a yellow oil which was determined by HPLC to be a 5:1 mixture of regioisomers by HPLC.

##STR00050##

2-Fluoro-5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)-4-methylpyridazin-3-yl)benzonitrile

[0290] To a solution of 6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)-5-methylpyridazin-3-amine (0.8 g, 2.7 mmol, 1.0 equiv) and 2M aqueous K.sub.2CO.sub.3 (2.0 mL, 8.2 mmol, 3.0 equiv) in dioxane (14 mL) was added Pd(dppf)Cl.sub.2 (0.11 g, 0.14 mmol, 0.05 equiv) and 3-cyanophenylboronic acid (0.48 g, 3.3 mmol, 1.2 equiv). The mixture was stirred at 80 C. for 2 hours under a blanket of nitrogen. This was followed by addition of another 100 mg (0.68 mmol, 0.25 equiv) of the boronic acid and 30 mg (0.037 mmol, 0.013 equiv) of Pd(dppf)Cl.sub.2 and another 1 h of heating at 100 C. The mixture was allowed to cool to room temperature. and then was diluted with EtOAc. The solution was washed with 50% NaCl solution, dried over Na.sub.2SO.sub.4 and evaporated to dryness. The residue was purified by over silica gel using a 20-50% EtOAc/hexanes stepwise gradient to give the desired product (850 mg, 86%) as a single regioisomer.

##STR00051##

3-(6-(2-(4-Fluorophenyl)-2-methylpropylamino)-4-methylpyridazin-3-yl)benzamide

[0291] A 0 C. solution of 2-fluoro-5-(6-(2-(4-fluorophenyl)-2-methylpropylamino)-4-methylpyridazin-3-yl)benzonitrile (0.80 g, 2.2 mmol, 1.0 equiv), 30% hydrogen peroxide (0.45 mL, 4.4 mmol, 2.0 equiv), and K.sub.2CO.sub.3 (600 mg, 4.4 mmol, 2.0 equiv) in DMSO (9.0 mL) was stirred for 1 hour. The mixture was diluted with EtOAc, washed with saturated NaCl, water and saturated NaCl again, and then dried over Na.sub.2SO.sub.4. Purification by reverse phase HPLC using a gradient of 20-70% CH.sub.3CN/water gave the desired product (420 mg, 51%) as a yellow solid. m/z=379.1 [M+H]+.

EXAMPLE 15: PREPARATION OF 3-(5-CYANO-6-(2-(4-FLUOROPHENYL)-2-METHYLPROPYLAMINO)PYRIDAZIN-3-YL)BENZAMIDE

[0292] ##STR00052##

3,6-Dichloropyridazine-4-carboxamide

[0293] A solution of NH.sub.4OH (1.1 mL, 17 mmol, 1.2 equiv) and diisopropylethylamine (6.2 mL, 36 mmol, 2.1 equiv) in THF (57 mL) was sonicated until homogeneous after which was added DMAP (1.0 g, 14 mmol, 1.0 equiv). 3,6-dichloropyridazine-4-carbonyl chloride (3.0 g, 14 mmol, 1.0 equiv) was then added and the solution was stirred at room temperature for 20 minutes. The solution was filtered and partitioned between EtOAc and 1M KHSO.sub.4 solution. The organic layer was washed once more with 1M KHSO.sub.4 and saturated NaCl, dried over Na.sub.2SO.sub.4, and evaporated to dryness to give the desired product (2.6 g, 96%).

##STR00053##

6-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carboxamide

[0294] Using a similar procedure as was used for 6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)-5-methylpyridazin-3-amine in example 14, 3,6-dichloropyridazine-4-carboxamide (2.6 g, 13 mmol, 1.0 equiv), (2-(4-fluorophenyl)-2-methylpropan-1-amine (2.5 g, 15 mmol, 1.1 equiv), and diisopropylethylamine (2.8 mL, 16 mmol, 1.2 equiv) in CH.sub.3CN (54 mL) was heated at 60-90 C. for 48 hours. The product was purified over silica gel with 100% EtOAc to give the desired product (3.4 g, 78%) as a yellow foamy solid.

##STR00054##

6-Chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carbonitrile

[0295] To a portion of 6-chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carboxamide (3.4 g, 11 mmol, 1.0 equiv) was added POCl.sub.3 (10 mL) at room temperature. The mixture was stirred at reflux for 3 hours and then quenched by pouring it into ice water containing NaHCO.sub.3. Dioxane and EtOAc were added to facilitate mixing of the layers. The layers were allowed to separate and the aqueous layer was extracted with EtOAc and the combined organic phases were washed with saturated NaCl. The organics were dried over Na.sub.2SO.sub.4 and evaporated to dryness in vacuo. Purification over silica gel using a gradient of 10-20% EtOAc/hexanes yielded the desired product (0.60 g, 19%) as a yellow oil.

##STR00055##

3-(5-Cyano-6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)benzamide

[0296] To a solution of 6-chloro-3-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazine-4-carbonitrile (550 mg, 1.8 mmol, 1.0 equiv), 3-aminocarbonylphenylboronic acid, pinacol ester (330 mg, 2.0 mmol, 1.1 equiv) and aqueous K.sub.2CO.sub.3 (2.0M, 5.0 mL, 5.4 mmol, 3.0 equiv) in dioxane (18 mL) was added Pd(dppf)Cl.sub.2 (150 mg, 0.18 mmol, 0.1 equiv). The mixture was stirred at 120 C. for 10 minutes in a microwave and allowed to cool to room temperature. The solvents were evaporated in vacuo, and the residue was dissolved in dichloromethane. The solution was filtered and the solvent dried over Na.sub.2SO.sub.4. Purification over silica gel using a gradient of 40-80% EtOAc/hexanes gave a yellow solid that was slurried with CH.sub.3CN to give the desired product (30 mg, 4.3%) as a yellow solid. m/z=390.2 [M+H]+.

EXAMPLE 16: PREPARATION OF (S)-2-(4-FLUOROPHENYL)PROPAN-1-AMINE

[0297] ##STR00056##

(S)-4-Benzyl-3-(2-(4-fluorophenyl)acetyl)oxazolidin-2-one

[0298] To a cooled (78 C.) solution of (S)-4-benzyloxazolidin-2-one (10 g, 58 mmol, 1.0 equiv) in 100 mL THE was added dropwise n-BuLi (40 mL, 1.6M in hexanes, 64 mmol, 1.1 equiv). After stirring for 30 minutes, 4-fluorophenylacetyl chloride (10 g, 0.58 mmol, 1.0 equiv) was added dropwise. After stirring for an additional 30 minutes, the reaction mixture was allowed to warm to room temperature. The reaction was quenched with saturated aq. NH.sub.4Cl, extracted with dichloromethane, and washed with brine. The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel (10-20% EtOAc/hexanes) provided the title compound as a thick oil (14.7 g, 81%).

##STR00057##

(S)-4-Benzyl-3-((S)-2-(4-fluorophenyl)propanoyl)oxazolidin-2-one

[0299] To a room-temperature solution of (S)-4-benzyl-3-(2-(4-fluorophenyl)acetyl)oxazolidin-2-one (5.1 g, 16.3 mmol, 1.0 equiv) in dry THF (100 mL) was added iodomethane (1.0 mL, 16.2 mmol, 1.0 equiv) by syringe. The resulting mixture was cooled to 78 C., and NaHMDS (8.15 mL, 2M in THF, 16.3 mmol, 1.0 equiv) was added dropwise by syringe. After stirring for 15 minutes at 78 C., the reaction mixture was allowed to warm to room temperature. The reaction was quenched with saturated aq. NH.sub.4Cl, and diluted with EtOAc. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. Purification by silica gel chromatography (7-20% EtOAc/hexanes) provided the title compound (2.6 g, 49%).

##STR00058##

(S)-2-(4-Fluorophenyl)propan-1-ol

[0300] To a room-temperature solution of (S)-4-benzyl-3-((S)-2-(4-fluorophenyl) propanoyl)oxazolidin-2-one (1.8 g, 5.5 mmol, 1.0 equiv) in THF (18 mL) was added a solution of NaBH.sub.4 (1.0 g, 26.4 mmol, 4.8 equiv) in water (6.0 mL). The reaction mixture was stirred for 3 h at room temperature and then quenched by the careful addition of aq. 1M HCl. The reaction mixture was diluted with water and ethyl acetate. The layers were separated and the organic layer was subsequently washed with brine, dried over Na.sub.2SO.sub.4, filtered and concentrated in vacuo. Purification by silica gel chromatography (10-75% EtOAc/Hexanes) provided the title compound (0.824 g, 97%).

##STR00059##

(S)-2-(2-(4-Fluorophenyl)propyl)isoindoline-1,3-dione

[0301] To a solution of (S)-2-(4-fluorophenyl)propan-1-ol (0.82 g, 5.35 mmol, 1.0 equiv), phthalimide (0.82 g, 5.6 mmol, 1.05 equiv), and triphenyl phosphine (2.1 g, 8.03 mmol, 1.5 equiv) in dry THF (18 mL) was added dropwise diethylazodicarboxylate (3.6 mL, 15% in toluene, 8.0 mmol, 1.5 equiv). The reaction mixture was stirred over 72 h and then concentrated in vacuo. Purification by silica gel chromatography (15-25% EtOAc/Hexanes) provided the title compound (0.9 g, 59%).

##STR00060##

(S)-2-(4-Fluorophenyl)propan-1-amine

[0302] To a room-temperature solution of (S)-2-(2-(4-fluorophenyl)propyl)isoindoline-1,3-dione (900 mg, 3.2 mmol, 1.0 equiv) in toluene (14 mL) was added hydrazine hydrate (1.4 mL, 45 mmol, 14 equiv) by syringe. The resulting mixture was heated to 80 C. for 30 minutes and then cooled to room temperature. The resulting solution was decanted from the solid in the reaction mixture, and the solid was washed with additional toluene. The combined organic layers were combined and concentrated in vacuo to provide the title compound (491 mg, 99%), which was used without further purification.

EXAMPLE 17: PREPARATION OF 2-(4-FLUOROPHENYL)-2-METHYLPROPAN-1-AMINE

[0303] ##STR00061##

[0304] To a solution of 4-fluorophenylacetonitrile (50 g, 370 mmol, 1.0 equiv) and iodomethane (70 mL, 1.1 mol, 3 equiv) in THE (370 mL) was added KOt-Bu (124 g, 1.1 mol, 3 equiv) as a solid in portions such that the reaction mixture did not exceed 50 C. The reaction mixture was stirred overnight and then quenched by the addition of brine. The mixture was diluted with EtOAc and washed twice with brine. The organic layer was dried over Na.sub.2SO.sub.4, filtered, and concentrated in vacuo to provide 2-(4-fluorophenyl)-2-methylpropanenitrile as a yellow oil (57 g, 94%), which was used without further purification in the next step. To a solution of the nitrile in dry THF (800 mL) was added a solution of lithium aluminum hydride (210 mL, 2M in ether, 420 mmol, 1.2 equiv). After the mixture was heated at reflux overnight, the reaction was allowed to cool to room temperature, and a Fieser and Fieser work-up (300 uL water/mmol, 1.0 mL 3N NaOH/mmol, 300 uL water/mmol) was performed. Filtration of the resulting solids provided the title compound as an orange oil (57 g, 92%).

EXAMPLE 18: PREPARATION (1-(4-FLUOROPHENYL)CYCLOBUTYL)METHANAMINE

[0305] ##STR00062##

[0306] A solution of 4-fluorophenylacetonitrile (6.7 g, 75 mmol, 1.5 equiv), 1,3-dibromopropane (10 mL, 50 mmol, 1 equiv), KOH (27 g, 150 mmol, 3.0 equiv), and tetrabutylammonium bromide (100 mg) in toluene (135 mL) was heated to 100 C. for 3 hours. The organic layer was separated and concentrated to dryness. Silica gel chromatography using a gradient of 0-30% EtOAc/hexanes resulted in partially purified product which was further purified by Kugelrohr distillation at 200 C. to provide 3.76 g (22 mmol) of the intermediate nitrile product as an oil. The residue was dissolved in dry THF (22 mL) and treated with a solution of LAH (27 mL, 2M in ether, 55 mmol, 2.5 equiv). The mixture was stirred at 0 C. for 2 hours followed by a Fieser and Fieser work-up (38 uL water/mmol, 118 uL 3N NaOH/mmol, 38 uL water/mmol). The organic layer was concentrated to dryness to provide the desired product (3.6 g, 40% overall) as a yellow oil.

EXAMPLE 19: PREPARATION OF (1-(6-METHOXYPYRIDIN-2-YL)CYCLOBUTYL)METHANAMINE

[0307] ##STR00063##

1-(6-Fluoropyridin-2-yl)cyclobutanecarbonitrile

[0308] Following the same procedure as described for 2-(3-fluoropyridin-2-yl)acetonitrile (Example 18), 2,6-difluoropyridine (5.0 g, 43 mmol, 1.0 equiv), cyclobutylcarbonitrile (3.5 g, 43 mmol, 1.0 equiv) and NaHMDS (2.0M in THF, 24 mL, 47 mmol, 1.1 equiv) in toluene (100 mL) gave the desired product (4.9 g, 64%) as a colorless oil following purification over silica gel using 25% EtOAc/hexanes as eluent.

##STR00064##

1-(6-Methoxypyridin-2-yl)cyclobutanecarbonitrile

[0309] To stirred 6.0 mL of anhydrous methanol at 0 C. under nitrogen was added sodium metal (1 g) and the mixture stirred for 30 minutes. To this was added 1-(6-fluoropyridin-2-yl)cyclobutanecarbonitrile (1.6 g, 9.1 mmol) and the resulting mixture heated to 75 C. for 45 minutes. The solution was cooled to room temperature and partitioned between water and EtOAc. The layers were separated, the aqueous phase was extracted with EtOAc, and the combined organic phases were washed with saturated NaCl, dried over Na.sub.2SO.sub.4 and concentrated in vacuo to give the desired product (1.7 g, 97%) as a colorless oil.

##STR00065##

(1-(6-Methoxypyridin-2-yl)cyclobutyl)methanamine

[0310] To a stirred solution of 1-(6-methoxypyridin-2-yl)cyclobutanecarbonitrile (1.7 g, 8.8 mmol, 1.0 equiv) in THF (20 mL) was added lithium aluminum hydride solution (1.0M in THF, 11 mL, 11 mmol, 1.1 equiv). The mixture was refluxed for 1.5 hours and allowed to cool to room temperature. Water (0.43 mL) was added slowly followed by 0.43 mL of 3M NaOH and then three additions of 0.43 mL of water (Fieser and Fieser workup). The resulting mixture was filtered through diatomaceous earth and rinsed with THF. The combined organics were dried over Na.sub.2SO.sub.4 and concentrated to dryness to give the desired product (1.6 g, 97%) as a viscous oil.

EXAMPLE 20: PREPARATION OF 1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTANAMINE

[0311] ##STR00066##

1-(3-Fluoropyridin-2-yl)cyclobutanecarboxamide

[0312] To a 250 mL round bottom flask containing DMSO (60 mL), 1-(3-fluoropyridin-2-yl)cyclobutanecarbonitrile (2.96 g, 16.8 mmol, 1.0 equiv) was added and the mixture was stirred until homogenous. Potassium carbonate (7.0 g, 50.4 mmol, 3.0 equiv) was then added and the reaction mixture was cooled to 0 C., followed by the addition of 35% hydrogen peroxide (6.5 mL). The reaction was stirred at 0 C. for 30 min and then warmed to room temperature. At this time, the reaction was diluted with water (50 mL) and ethyl acetate (100 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer and then washed with brine (350 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel chromatography (10% EtOAC/hexanes) to afford 1.92 g (59%) of 1-(3-fluoropyridin-2-yl)cyclobutanecarboxamide as a white solid.

##STR00067##

Methyl 1-(3-fluoropyridin-2-yl)cyclobutylcarbamate

[0313] 1-(3-fluoropyridin-2-yl)cyclobutanecarboxamide (1.92 g, 9.88 mmol, 1.0 equiv) was dissolved in methanol (20 mL) and potassium hydroxide (1.11 g, 19.8 mmol, 2.0 equiv) was added. The mixture was sonicated until homogeneous, followed by the addition of iodosobenzene diacetate (4.77 g, 14.8 mmol, 1.5 equiv). The reaction was stirred for 20 min and then diluted with water (100 mL) and ethyl acetate (125 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer, and the aqueous layer was extracted with EtOAc (50 mL). The combined organic layers were then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude oil that was purified by silica gel chromatography (40% EtOAC/hexanes) to afford 1.47 g (67%) of methyl 1-(3-fluoropyridin-2-yl)cyclobutylcarbamate as a white solid.

##STR00068##

1-(3-Fluoropyridin-2-yl)cyclobutanamine

[0314] To a 20 mL microwave reaction vial was added methyl 1-(3-fluoropyridin-2-yl)cyclobutylcarbamate (1.47 g, 6.56 mmol), ethanol (12 mL) and 3N aqueous sodium hydroxide (7 mL). The reaction mixture was heated in the microwave reactor at 150 C. for 30 min. The ethanol was evaporated under reduced pressure and the mixture was extracted with ethyl acetate (30 mL). The aqueous layer was then extracted with ethyl acetate (230 mL). The organic layers were combined, dried over Na.sub.2SO.sub.4, filtered, and concentrated to give 1-(3-fluoropyridin-2-yl)cyclobutanamine (1.01 g, 93%) as a crude yellow oil that was used in the next reaction step without further purification.

EXAMPLE 21: PREPARATION OF 2-(3-FLUOROPYRIDIN-2YL)ACETONITRILE

[0315] ##STR00069##

[0316] To a 0 C. solution of 2-chloro-3-fluoropyridine (3.0 g, 23 mmol, 1.0 equiv) and acetonitrile (1.3 mL, 25 mmol, 1.1 equiv) in toluene (50 mL) was added sodium hexamethyldisilazide (NaHMDS) (2.0M in THF, 13 mL, 25 mmol, 1.1 equiv). The resulting mixture was stirred for 2 hours at 0 C. and then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic phases were washed with saturated NaCl, dried over Na.sub.2SO.sub.4 and concentrated in vacuo to provide the crude desired product as an oil which was used without further purification.

EXAMPLE 22: PREPARATION OF 6-CHLORO-N-(2-PHENYLPROPAN-2-YL)PYRIDAZIN-3-AMINE

[0317] ##STR00070##

[0318] To a 5 mL microwave reaction vial was added 3,6-dichloropyridazine (544 mg, 3.7 mmol, 1.0 equiv), cumylamine (500 mg, 3.7 mmol, 1.0 equiv), and DIPEA (640 L, 3.7 mmol, 1.0 equiv). The reaction was heated in a microwave reactor to 225 C. for 15 min and then diluted with brine (20 mL) and extracted with ethyl acetate (40 mL). The organic layer was dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel column chromatography (20% EtOAc/hexanes) to yield 48 mg (5%) of 6-chloro-N-(2-phenylpropan-2-yl)pyridazin-3-amine as a white solid.

EXAMPLE 23: PREPARATION OF 2-(2-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)THIAZOL-5-YL)ACETAMIDE

[0319] ##STR00071##

5-((t-Butyldimethylsilyloxy)methyl)thiazole

[0320] Thiazole-5-methanol (65 g, 0.56 mol), imidazole (58 g, 0.85 mol), and CH.sub.2Cl.sub.2 (700 mL) were added to a round bottom flask, followed by TBSCl (93 g, 0.62 mol). The reaction was stirred for 20 min and the resultant white solid was filtered off. The filtrate was washed with saturated sodium bicarbonate, dried over sodium sulfate, concentrated, and purified by silica gel chromatography (10% EtOAC/hexanes) to afford 140 g of 5-((t-butyldimethylsilyloxy)methyl)thiazole as a clear oil.

##STR00072##

t-butyl 6-(5-((t-butyldimethylsilyloxy)methyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0321] To a stirring mixture of THF (2000 mL) and diisopropylamine (79.3 mL, 0.56 mol) at 78 C. was added n-BuLi (244 mL, 0.56 mol) dropwise. After stirring for 20 min at 78 C., a solution of 5-((t-butyldimethylsilyloxy)methyl)thiazole (110.9 g, 0.49 mol in 300 mL of THF) was added dropwise to the reaction mixture while maintaining a temperature less than 70 C. After the addition was complete, the reaction was stirred for an additional 30 min and a solution of zinc bromide (126.6 g, 0.56 mol in 300 mL of THF) was added dropwise to the reaction mixture while maintaining a temperature less than 65 C. The reaction was warmed to 0 C., stirred for 30 min, and added to a stirring mixture of t-butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (100 g, 0.26 mol), tetrakis(triphenylphosphine)palladium(0) (56 g, 0.05 mol), and THF (2000 mL) heated to 80 C. The reaction mixture was stirred overnight at 80 C. The reaction was concentrated and then slurried in ethyl acetate and brine. The resultant solid was filtered off, and the filtrate was dried over sodium sulfate, concentrated, and purified twice by silica gel chromatography (EtOAc/hexanes) to afford 112.5 g of t-butyl 6-(5-((tert-butyldimethylsilyloxy)methyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a dark oil.

##STR00073##

t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-(hydroxymethyl)thiazol-2-yl)pyridazin-3-yl)carbamate

[0322] To a solution of t-butyl 6-(5-((tert-butyldimethylsilyloxy)methyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (112.5 g, 0.19 mol) in THF (1000 mL) was added TBAF (105 mL, 0.29 mol, 75% w/w). The reaction was stirred for 30 min followed by the addition of ammonium chloride (200 mL). The organic layer was separated, washed with brine (300 mL3), and concentrated (this wash was repeated once). Ethyl acetate was added to the oil, resulting in a white solid. Filtration of the solid afforded 44 g of t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-(hydroxymethyl)thiazol-2-yl)pyridazin-3-yl)carbamate.

##STR00074##

t-butyl 6-(5-(chloromethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0323] To a solution of t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-(hydroxymethyl)thiazol-2-yl)pyridazin-3-yl)carbamate (44.1 g, 93.8 mmol) in dioxane (235 mL) was added thionyl chloride (27.3 mL, 375.3 mmol). The reaction was stirred until it was homogeneous. The reaction was then slowly quenched by pouring into a mixture of saturated potassium carbonate solution and ethyl acetate. The organic layer was then separated, dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography (EtOAC/hexanes) to afford 33.1 g of t-butyl 6-(5-(chloromethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a white solid.

##STR00075##

t-butyl 6-(5-(cyanomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0324] To a solution of t-butyl 6-(5-(chloromethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (33.1 g, 68 mmol) in CH.sub.2Cl.sub.2 (450 mL) was added tetrabutylammonium cyanide (36 g, 135 mmol). The reaction was heated to 45 C. and stirred for 1 h, followed by concentration and purification by silica gel chromatography (EtOAc/hexanes) to afford 13.4 g of t-butyl 6-(5-(cyanomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as an off-white solid.

##STR00076##

2-(2-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiazol-5-yl)acetamide

[0325] To a solution of t-butyl 6-(5-(cyanomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (12.5 g, 26.0 mmol) in DMSO (260 mL) was added potassium carbonate (14.4 g, 104.1 mmol). The mixture was cooled to 0 C. and hydrogen peroxide (86 mL) was slowly added. The reaction was warmed to rt and stirred for 90 min. The reaction was diluted with EtOAc (200 mL) and water (500 mL), and the organic layer was washed three times with brine (150 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was purified by silica gel chromatography (CH.sub.3CN/CH.sub.2Cl.sub.2) to afford 6.2 g of t-butyl 6-(5-(2-amino-2-oxoethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a reddish solid. This compound was combined with other batches (15.5 g overall), dissolved in 25% TFA/CH.sub.2Cl.sub.2, and stirred for 1 h. The reaction was then concentrated, dissolved in ethyl acetate (75 mL), and washed three times with potassium carbonate. The organic layer was then dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude solid that was recrystallized with THF to give 10.8 g of 1-(2-((-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyrimidin-5-yl)-1H-pyrrole-3-carboxamide as an off-white solid (M+H=399.1).

EXAMPLE 24: PREPARATION OF 2-(2-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)THIAZOL-5-YL)-N-METHYLACETAMIDE

[0326] ##STR00077##

[0327] A solution of t-butyl 6-(5-(cyanomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (1 g, 2 mmol) in HCl (30 mL, conc) was heated to 105 C. in a microwave reactor and stirred for 15 min. The reaction was concentrated to give 900 mg (2.3 mmol) of a crude reddish solid. To this solid was added methylamine hydrochloride (183 mg, 2.7 mmol), HOBt (365 mg, 2.7 mmol), EDC (516 mg, 2.7 mmol), DMF (30 mL), and TEA (1.3 mL, 9 mmol). The reaction was stirred at rt overnight. The reaction was then poured into ethyl acetate (200 mL), washed with water (3100 mL), and the organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, concentrated, and recrystallized from EtOAc to give 408 mg of 2-(2-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiazol-5-yl)-N-methylacetamide as a white solid (M+H=413.3).

EXAMPLE 25: PREPARATION OF N-((2-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)THIAZOL-5-YL)METHYL)-2-HYDROXYACETAMIDE

[0328] ##STR00078##

t-butyl 6-(5-(Azidomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0329] To a stirring solution of t-butyl 6-(5-(chloromethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (60.7 g, 124 mmol) in DMF (800 mL) was added sodium azide (22.2 g, 341 mmol) and DIPEA (31.1 mL, 171 mmol). The reaction was heated to 60 C. and stirred for 1 h. The reaction was poured into ethyl acetate (2000 mL), washed with water (3400 mL), and the combined organic layers were separated, dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography (EtOAC/hexanes) to afford 20.0 g of t-butyl 6-(5-(azidomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a yellow oil.

##STR00079##

t-butyl 6-(5-(Aminomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0330] Tin(II) chloride dihydrate (15.5 g, 80 mmol) was added to a solution of t-butyl 6-(5-(azidomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (20 g, 40 mmol) in methanol (400 mL) and the reaction was stirred at rt for 30 min. The reaction was poured into ethyl acetate (1000 mL), washed with water (3200 mL), and the combined organic layers were separated, dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified using silica gel column chromatography (9% MeOH/90% EtOAc/1% TEA) to give 35 g of t-butyl 6-(5-(aminomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a yellow oil.

##STR00080##

N-((2-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiazol-5-yl)methyl)-2-hydroxyacetamide

[0331] t-butyl 6-(5-(aminomethyl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (4.8 g, 10 mmol), glycolic acid (0.9 g, 12 mmol), HOBt (1.6 g, 12 mmol), EDC (2.3 g, 12 mmol), DMF (50 mL), and TEA (5.9 mL) were added to a 250 mL round bottom flask and the reaction was heated to 60 C. and stirred for 1 h. The reaction was poured into ethyl acetate (400 mL), washed with water (3100 mL), and the combined organic layers were separated, dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography (EtOAC/hexanes) to afford 3.9 g of t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-((2-hydroxyacetamido)methyl)thiazol-2-yl)pyridazin-3-yl)carbamate as a white solid. This compound was dissolved in 30% TFA/CH.sub.2Cl.sub.2 (30 mL) and stirred for 1 h. The reaction was concentrated, dissolved in EtOAc (200 mL), washed with potassium carbonate (330 mL), concentrated, and then recrystallized with ethanol to give a white solid that was further purified with reverse phase chromatography to give 305 mg of N-((2-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiazol-5-yl)methyl)-2-hydroxyacetamide as a white solid (M+H=429.1).

EXAMPLE 26: PREPARATION OF 1-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)-1H-PYRROLE-3-CARBOXAMIDE

[0332] ##STR00081##

t-butyl 6-(3-Cyano-1H-pyrrol-1-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0333] To a stirring solution of t-butyl 6-fluoropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (200 mg, 551 mol) in DMF (2 mL) was added 3-cyanopyrrole (61 mg, 661 mol) and potassium carbonate (152 mg, 1.1 mmol). The reaction was heated to 110 C. and stirred for 30 min. The reaction was then poured into ethyl acetate (100 mL), washed with water (325 mL), and the organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography (EtOAC/hexanes) to afford 130 mg of t-butyl 6-(3-cyano-1H-pyrrol-1-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a pale yellow solid.

##STR00082##

1-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-pyrrole-3-carboxamide

[0334] t-butyl 6-(3-cyano-1H-pyrrol-1-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (120 mg, 267 mol), potassium carbonate (147 mg, 1.1 mmol), and DMSO (3 mL) were combined in a vial and cooled to 0 C. Hydrogen peroxide (700 uL) was added dropwise, and the reaction was warmed to rt and stirred for 1 h. The reaction was then poured into ethyl acetate (50 mL), washed with water (320 mL), and the organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, and concentrated. The crude solid was dissolved in 50% TFA/CH.sub.2Cl.sub.2 (2 mL) and stirred for 30 min. The reaction was then concentrated and purified using reverse phase chromatography to give 29 mg of 1-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-pyrrole-3-carboxamide as a tan solid (M+H=367.1).

EXAMPLE 27: PREPARATION OF 2-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)-4-HYDROXY-2,5-DIHYDROTHIAZOLE-5-CARBOXAMIDE

[0335] ##STR00083##

t-butyl 6-Cyanopyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0336] To a solution of 6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazine-3-carbonitrile (3.3 g, 4.7 mmol) in THF (30 mL) was added di-t-butyl dicarbonate (2.8 g, 13 mmol), and DMAP (0.5 g, 4.3 mmol). The reaction mixture was refluxed for 2 h. The reaction was concentrated and then poured into ethyl acetate (150 mL) and washed with 0.1M HCl (50 mL, aq) and brine (50 mL). The organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude oil that was purified by silica gel column chromatography (EtOAC/hexanes) to afford 3.9 g of t-butyl 6-cyanopyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a white solid.

##STR00084##

t-butyl 6-Carbamothioylpyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0337] NMP (40 mL) and DIPEA (10 mL) were added to t-butyl 6-cyanopyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (3.9 g, 10 mmol), and hydrogen sulfide was bubbled through the reaction mixture for 2 h. The reaction was diluted with water, and the resultant yellow solid was filtered and dried under vacuum to give 2.1 g of t-butyl 6-carbamothioylpyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate as a yellow solid.

##STR00085##

Ethyl 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxylate

[0338] t-Butyl 6-carbamothioylpyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (1.0 g, 2.4 mmol), diethylbromomalonate (2 mL, 12 mmol), and toluene were added to a round bottom flask, heated to 90 C., and stirred for 40 min. The reaction was concentrated and purified using reverse phase chromatography to yield 219 mg of ethyl 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxylate as an off-white solid.

##STR00086##

2-(6-(t-Butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylic acid

[0339] To a stirring solution of ethyl 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxylate (350 mg, 0.7 mmol) in DMF (4 mL) was added methyl iodide (200 L, 3.3 mmol) and sodium hydride (60% dispersion in mineral oil, 40 mg, 1 mmol). The reaction was stirred at rt for 1 h and at 40 C. for 45 min. The reaction was then concentrated and quenched with water (5 mL), poured into ethyl acetate (150 mL), and washed with 0.1M HCl (50 mL, aq) and brine (50 mL). The organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, concentrated and purified by silica gel column chromatography (EtOAC/hexanes) to afford 205 mg of ethyl 2-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylate. This compound was dissolved in methanol (4 mL) and 1M KOH (aq, 2 mL). The reaction mixture was heated to 75 C. and stirred for 45 min. The reaction was cooled and the pH was adjusted to 4 using 1M HCl. The reaction was then poured into ethyl acetate (50 mL), washed with brine (15 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated to give 175 mg of 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylic acid as a white foam.

##STR00087##

t-butyl 6-(5-Carbamoyl-4-methoxy-2,5-dihydrothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0340] To a 50 dram vial was added 2-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-methoxy-2,5-dihydrothiazole-5-carboxylic acid (175 mg, 0.34 mmol), HATU (194 mg, 0.51 mmol), HOAt (70 mg, 0.51 mmol), DIPEA (296 L, 1.7 mmol), NMP (2 mL), and ammonium chloride (180 mg, 3.4 mmol). The reaction was stirred overnight at rt. The reaction was then poured into ethyl acetate (50 mL), washed with aqueous sodium bicarbonate, and brine (50 mL). The organic layer was separated, dried over Na.sub.2SO.sub.4, filtered, concentrated and purified by silica gel column chromatography (EtOAC/hexanes) to afford 120 mg of t-butyl 6-(5-carbamoyl-4-methoxy-2,5-dihydrothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate.

##STR00088##

2-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxamide

[0341] To a stirring mixture of t-butyl 6-(5-carbamoyl-4-methoxy-2,5-dihydrothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (60 mg, 0.12 mol) in CH.sub.2Cl.sub.2 (2 mL) was added BBr.sub.3 (140 L, 1.2 mmol). The reaction was stirred at rt for 2 h and then at 60 C. for 15 min. The reaction was cooled to rt and carefully diluted with methanol (2 mL). The reaction was concentrated, diluted with ethyl acetate (20 mL), and saturated sodium bicarbonate (10 mL) was added. The mixture was agitated and then filtered. The subsequent crude solid was then purified using reverse phase chromatography to give 15 mg of 2-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-4-hydroxy-2,5-dihydrothiazole-5-carboxamide as a yellow solid (M+H=401.3)

EXAMPLE 28: PREPARATION OF 4-FLUORO-3-(6-(((TRANS)-3-FLUORO-1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)-2-HYDROXYBENZAMIDE

[0342] ##STR00089##

t-butyl 6-(3-Bromo-6-fluoro-2-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0343] t-Butyl 6-Bromopyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (3.0 g, 6.61 mmol), 3-bromo-6-fluoro-2-methoxyphenylboronic acid (1.64 g, 6.61 mmol), (dppf)PdCl.sub.2 (0.48 g, 0.66 mmol), nitrogen-sparged dioxane (13.2 mL) and aq. 2N K.sub.2CO.sub.3 (0.6 mL) were combined and heated in a microwave reactor at 125 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography afforded the title compound as a yellow solid (1.4 g, 37%), (m/z [M+H]=579.1).

##STR00090##

t-butyl 6-(3-cyano-6-fluoro-2-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0344] t-Butyl 6-(3-Bromo-6-fluoro-2-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (1.4 g, 3.0 mmol), zinc cyanide (0.42 g, 3.6 mmol), Pd(PPh.sub.3).sub.4(1.0 g, 0.9 mmol), DMF (3 mL) were combined and heated to 100 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography afforded the title compound as a yellow solid (1.0 g, 63%), (m/z [M+H]=526.2).

##STR00091##

t-butyl 6-(3-carbamoyl-6-fluoro-2-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0345] t-Butyl 6-(3-cyano-6-fluoro-2-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (1.0 g, 1.9 mmol), K.sub.2CO.sub.3 (0.8 g, 5.8 mmol), and DMSO (10 mL) were combined in a round bottom flask, cooled to 0 C., and H.sub.2O.sub.2 (2 mL of 35% solution) was added dropwise. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography afforded the title compound as a white solid (0.32 g, 33%), (m/z [M+H]=545.1).

##STR00092##

4-Fluoro-3-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-2-hydroxybenzamide

[0346] t-Butyl 6-(3-carbamoyl-6-fluoro-2-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (0.32 g, 0.59 mmol), lithium iodide (0.71 g, 5.34 mmol), and pyridine (5 mL) were combined in a microwave reactor and heated to 125 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Reverse phase chromatography provided 4-fluoro-3-(6-(((E)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-2-hydroxybenzamide as a white solid (0.024 g, 10%), (m/z [M+H]=430.1).

EXAMPLE 29: PREPARATION OF 4-FLUORO-5-(6-(((TRANS)-3-FLUORO-1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)-2-HYDROXYBENZAMIDE

[0347] ##STR00093##

t-Butyl 6-(5-bromo-2-fluoro-4-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0348] t-Butyl 6-bromopyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (3.0 g, 6.61 mmol), 2-(5-bromo-2-fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.2 g, 6.61 mmol), (dppf)PdCl.sub.2 (0.48 g, 0.66 mmol), nitrogen-sparged dioxane (13.2 mL) and aq. 2N K.sub.2CO.sub.3 (0.6 mL) were combined and heated to 90 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography provided a light yellow solid (1.7 g, 44%), (m/z [M+H]=579.1).

##STR00094##

t-Butyl 6-(5-cyano-2-fluoro-4-meth oxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0349] t-Butyl 6-(5-bromo-2-fluoro-4-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (1.7 g, 3.6 mmol), zinc cyanide (0.51 g, 4.3 mmol), Pd(PPh.sub.3).sub.4(1.26 g, 1.0 mmol), DMF (5 mL) were combined and heated to 100 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography provided a yellow solid (1.1 g, 66%), (m/z [M+H]=526.2).

##STR00095##

t-Butyl 6-(5-carbamoyl-2-fluoro-4-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0350] t-Butyl 6-(5-cyano-2-fluoro-4-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (0.21 g, 0.4 mmol), K.sub.2CO.sub.3 (0.22 g, 1.6 mmol), and DMSO (4 mL) were combined in a round bottom flask, cooled to 0 C., and H.sub.2O.sub.2(1.3 mL of 35%) was added dropwise. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography provided a white solid (0.10 g, 46%), (m/z [M+H]=545.1).

##STR00096##

4-Fluoro-5-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-2-hydroxybenzamide

[0351] t-Butyl 6-(5-carbamoyl-2-fluoro-4-methoxyphenyl)pyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (0.10 g, 0.18 mmol), lithium iodide (0.22 g, 1.65 mmol) and pyridine (3 mL) were combined in a microwave reactor and heated to 125 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Reverse phase chromatography provided the title compound as a white solid (0.023 g, 30%), (m/z [M+H]=430.1).

EXAMPLE 30: PREPARATION OF 5-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)-1H-PYRAZOLE-3-CARBOXAMIDE

[0352] ##STR00097##

t-Butyl 6-(1-ethoxyvinyl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0353] t-Butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (5.1 g, 13.0 mmol), tributyl(1-ethoxyvinyl)stannane (6.1 g, 16.9 mmol), (PPh.sub.3).sub.2PdCl.sub.2 (2.3 g, 3.2 mmol), and nitrogen-sparged dioxane (18 mL) were combined and heated in a microwave reactor at 150 C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography provided a light yellow solid (3.9 g, 71%), (m/z [M+H]=429.2).

##STR00098##

t-Butyl 6-acetylpyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0354] t-Butyl 6-(1-ethoxyvinyl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (1.0 g, 2.3 mmol), EtOH (75 mL), and 1N HCl (15 mL) were combined at 0 C., warmed to 25 C., and stirred for 1 h. The reaction mixture was concentrated and silica gel chromatography provided a colorless oil (0.6 g, 64%), (m/z [M+H]=401.1).

##STR00099##

Ethyl 5-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-1H-pyrazole-3-carboxylate

[0355] t-Butyl 6-acetylpyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (2.5 g, 6.2 mmol) in THF (150 mL) was treated with NaOEt (3.44 g, 10.6 mmol, 21% in EtOH). The resulting mixture was then treated with diethyl oxalate (1.7 mL, 12.5 mmol), heated to 45 C., and stirred for 4 h. The reaction mixture was added to 1N HCl, extracted with EtOAc, and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. A portion of the resultant oil was dissolved in AcOH and hydrazine (0.41 g, 13.2 mmol) was added and stirred at 80 C. Concentration afforded a yellow oil which was purified by reverse-phase chromatography to give solid (0.285 g, 62%), (m/z [M+H]=497.2).

##STR00100##

5-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-1H-pyrazole-3-carboxamide

[0356] Ethyl 5-(6-(t-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-1H-pyrazole-3-carboxylate (0.28 g, 0.56 mmol) and 7N ammonia in MeOH were combined in a microwave reactor and heated to 110 C. for 1 h. The reaction mixture was then concentrated, diluted with EtOAc, and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The resultant oil was diluted in 10 mL of DCM and TFA (15 mL) was added. The reaction mixture was then concentrated and purified by reverse phase chromatography to give the title compound as a white solid (18 mg, 12%), (m/z [M+H]=368.1).

EXAMPLE 31: PREPARATION OF 3-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)ISOXAZOLE-5-CARBOXAMIDE

[0357] ##STR00101##

t-Butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-vinylpyridazin-3-yl)carbamate

[0358] t-Butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (2.5 g, 6.36 mmol), triethenylboroxin pyridine complex (1.0 g, 4.13 mmol), Pd(PPh.sub.3).sub.4(0.3 g, 0.25 mmol), nitrogen-sparged dioxane (13.2 mL) and aq. 2N K.sub.2CO.sub.3 (0.9 mL) were combined and heated to 110 C. for 25 min. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography provided a light yellow oil (2.1 g, 86%), (m/z [M+H]=385.2).

##STR00102##

t-Butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-formylpyridazin-3-yl)carbamate

[0359] t-Butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-vinylpyridazin-3-yl)carbamate (3.4 g, 8.84 mmol) was added as a dioxane (100 mL) solution to a mixture of sodium periodate (10.8 g, 50.5 mmol) and 4% osmium tetraoxide solution (6.5 mL) in H.sub.2O (30 mL) at 0 C. The reaction was stirred for 2 h. The reaction mixture was filtered through a pad of celite and washed with EtOAc. The organic layer was washed with satd. aq. NaHCO.sub.3, brine and dried over sodium sulfate, filtered, and concentrated. Silica gel chromatography provided a colorless oil (1.4 g, 41%), (m/z [M+H]=387.2).

##STR00103##

Methyl-3-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)isoxazole-5-carboxylate

[0360] To t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-formylpyridazin-3-yl)carbamate (1.4 g, 3.6 mmol) in ethanol (10 mL) and water (2 mL) was added hydroxylamine hydrochloride (0.27 g, 3.8 mmol) followed by sodium acetate (0.32 g, 3.8 mmol) and stirred at 24 C. for 30 min. The crude reaction mixture was concentrated and diluted with EtOAc. The organic layer was washed with satd. aq. NaHCO.sub.3 and brine, then dried over sodium sulfate, filtered, and concentrated. The crude mixture was then diluted in THF (2 mL) and pyridine (57 mg, 0.72 mmol) then treated with NCS (0.58 g, 4.35 mmol) and heated to 40 C. for 1.5 h. The crude mixture was then treated with methyl propiolate (0.30 g, 3.56 mmol) and TEA (0.36, 3.56 mmol), and the reaction was stirred for 45 min. The reaction mixture was concentrated and diluted with EtOAc, and then washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified by reverse phase chromatography to give a white solid (0.53 g, 31%).

##STR00104##

3-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)isoxazole-5-carboxamide

[0361] Methyl 3-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)isoxazole-5-carboxylate (0.53 g, 1.1 mmol), methanol (5 mL) and concentrated ammonium hydroxide (8 mL) were combined in a microwave reactor and heated to 100 C. for 60 min. The reaction mixture was then concentrated and diluted with EtOAc and washed with satd. aq. NaHCO.sub.3 and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. Resultant oil was diluted in 10 mL of DCM and TFA (6 mL) was added and the reaction was stirred for 35 min. The reaction mixture was then concentrated and purified by reverse phase chromatography to give the title compound as a white solid (144 mg, 36%), (m/z [M+H]=369.1).

EXAMPLE 32: PREPARATION OF 2-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)THIAZOLE-5-CARBOXAMIDE

[0362] ##STR00105##

Ethyl 2-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)thiazole-5-carboxylate

[0363] tert-butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (500 mg, 1.27 mmol), ethyl thiazole-5-carboxylate (300 mg, 1.91 mmol), Pd(OAc).sub.2 (86 mg, 0.13 mmol), JohnPhos (92 mg, 0.26 mmol) and Cs.sub.2CO.sub.3 (827 mg, 2.54 mmol) in toluene (10 mL) were combined and heated in a microwave reactor for 30 min at 145 C. The reaction mixture was filtered through a celite plug and the filtrate was concentrated. The resulting residue was purified on silica gel using a mixture of ethyl acetate and hexanes to provide the title compound as yellow oil (162 mg, 82% pure, 21%), LRMS (M+H.sup.+) m/z 514.3.

##STR00106##

t-Butyl 6-(5-carbamoylthiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0364] To a solution of ethyl 2-(6-(tert-butoxycarbonyl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)thiazole-5-carboxylate (162 mg, 0.32 mmol) in MeOH (8 mL) was purged with NH.sub.3 gas for 5 min. The reaction mixture was sealed and heated in a microwave reactor for 30 min at 120 C. The reaction mixture was concentrated and used in next step without purification, LRMS (M+H.sup.+) m/z 484.2.

##STR00107##

2-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiazole-5-carboxamide

[0365] To a crude mixture of t-butyl 6-(5-carbamoylthiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (141 mg, crude) in DCM (6 mL) was added TFA (2 mL) at rt. The reaction mixture was further stirred at rt for 2 hr followed by concentration to dryness. The crude mixture was purified on RP-HPLC using a mixture of acetonitrile and H.sub.2O to provide the title compound as a pale yellow solid (98.5 mg, 99% for 2 steps), LRMS (M+H.sup.+) m/z 385.2.

EXAMPLE 33: PREPARATION OF 5-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)ISOXAZOLE-3-CARBOXAMIDE

[0366] ##STR00108##

Ethyl 5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)isoxazole-3-carboxylate

[0367] To t-butyl 6-(1-ethoxyvinyl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (439 mg, 1.02 mmol) in THF (5.0 mL) was added (E)-ethyl 2-chloro-2-(hydroxyimino)acetate (465 mg, 3.06 mmol) and TEA (1.4 mL, 10.2 mmol). The reaction mixture was stirred at rt for 30 min followed by addition of TFA (5 mL) and then heated to reflux overnight. The mixture was then concentrated and purified by reverse phase chromatography to give 415 mg of the title compound as a colorless oil, LRMS (M+H.sup.+) m/z 398.3.

##STR00109##

5-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)isoxazole-3-carboxamide

[0368] To a solution of ethyl 5-(6-((1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)isoxazole-3-carboxylate (200 mg, 0.40 mmol) in THF/MeOH mixture (12 mL, 5:1) was added LiOH (1M, 1.2 mL) at rt. The reaction mixture was stirred overnight and concentrated. To this crude mixture was added NH.sub.4Cl (60 mg, 1.2 mmol), HBTU (246 mg, 0.65 mmol), DIEA (132 uL, 0.8 mmol), and DMF (5.0 mL). The mixture was stirred at rt overnight, filtered, and purified by reverse phase chromatography to provide the title compound as a white solid (23.2 mg, 16%), LRMS (M+H.sup.+) m/z 369.2.

EXAMPLE 34: PREPARATION OF 5-(5-(6-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)THIOPHEN-2-YL)-2H-1,2,4-TRIAZOL-3(4H)-ONE

[0369] ##STR00110##

t-Butyl 6-(5-cyanothiophen-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0370] t-Butyl 6-chloropyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (900 mg, 2.29 mmol, 1 equiv), 5-cyanothiophen-2-ylboronic acid (390 mg, 2.52 mmol, 1.1 equiv), (dppf)PdCl.sub.2 (164 mg, 0.23 mmol, 0.1 equiv), nitrogen-sparged dioxane (6.0 mL) and aq. 2N K.sub.2CO.sub.3 (2.3 mL) were combined and heated in a microwave reactor for 30 min at 140 C. The reaction mixture was filtered through a Celite plug and the filtrate was concentrated. The resulting residue was purified on silica gel using a mixture of ethyl acetate and hexanes to provide the title compound as a yellow oil (340 mg, 32%), LRMS (M+H.sup.+) m/z 466.3.

##STR00111##

tert-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)thiophen-2-yl)pyridazin-3-yl)carbamate

[0371] To a solution of tert-butyl 6-(5-cyanothiophen-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (340 mg, 0.73 mmol, 1 equiv) in MeOH (10 mL) was added sodium methoxide (0.59 g, 1.1 mmol, 1.5 equiv). The reaction mixture was stirred at rt overnight followed by addition of hydrazine (0.5 mL). The mixture was then heated to reflux for 2 h and concentrated to dryness. The crude mixture was partitioned between EtOAc and water. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered, and concentrated. The crude product was dissolved in dioxane (3 mL), combined with CDI (137 mg, 1.46 mmol, 2 equiv), and heated for 4 h at 100 C. The mixture was cooled, filtered, and purified by reverse phase chromatography to give the title compound as a yellow solid (86 mg, 23% over 3 steps), LRMS (M+H.sup.+) m/z 524.3.

##STR00112##

5-(5-(6-((1-(3-Fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)thiophen-2-yl)-2H-1,2,4-triazol-3(4H)-one

[0372] To tert-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(5-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)thiophen-2-yl)pyridazin-3-yl)carbamate (86 mg, 0.16 mmol) in DCM (6 mL) was added TFA (2 mL) at rt. The reaction mixture was stirred at rt for 2 hr followed by concentration to dryness. The crude mixture was purified by reverse phase chromatography to provide the title compound as a pale yellow solid (73.6 mg, quantitative). LRMS (M+H.sup.+) m/z 424.2.

EXAMPLE 35: PREPARATION OF 4-FLUORO-3-(6-(((TRANS)-3-FLUORO-1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)-N-METHYLBENZAMIDE

[0373] ##STR00113##

1-(3-Fluoropyridin-2-yl)-3-methylenecyclobutanecarbonitrile

[0374] To a solution of 3-methylenecyclobutanecarbonitrile (150 g, 1.61 mol, 1 equiv) and 2-chloro-3-fluoropyridine (212 g, 1.61 mmol, 1 equiv) in toluene (1 L) was added NaHMDS (2M in THF, 885 mL, 1.1 equiv) dropwise at 0-10 C. Upon completion of addition, the reaction mixture was warmed to rt, stirred overnight, and quenched with NH.sub.4Cl.sub.(sat.) solution. The organic layer was washed with water (500 mL2) and brine (500 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated to give a crude title compound (272 g, 90%), which was used in the next step without further purification, LRMS (M+H.sup.+) m/z 189.1.

##STR00114##

1-(3-Fluoropyridin-2-yl)-3-oxocyclobutanecarbonitrile

[0375] To a mixture of 1-(3-fluoropyridin-2-yl)-3-methylenecyclobutanecarbonitrile (272 g, 1.45 mol) and RuCl.sub.3.H.sub.2O (9.0 g, 0.044 mol) in DCM (1 L), acetonitrile (1 L), and water (1.5 L) was added solid NaIO.sub.4 (1235 g, 5.8 mol) portionwise at 10-30 C. Upon completion of the addition, the reaction was stirred 1 h at 15 C. and overnight at rt. The solid precipitate was filtered off and washed with DCM (1 L2). The organic layer was washed with water (500 mL2) and brine (500 mL), dried over Na.sub.2SO.sub.4, and concentrated to provide the title compound as a crude dark solid (238 g, 86.3%), LRMS (M+H.sup.+) m/z 191.1.

##STR00115##

1-(3-Fluoropyridin-2-yl)-3-hydroxycyclobutanecarbonitrile

[0376] To a solution of 1-(3-fluoropyridin-2-yl)-3-oxocyclobutanecarbonitrile (231 g, 1.22 mol) in a mixture of DCM (2 L) and MeOH (200 mL) was added NaBH.sub.4 portion-wise at 78 C. The reaction mixture was stirred 1 h at 78 C. and then quenched with a mixture of methanol and water (1/1). The organic layer was washed with water (500 mL3), dried over Na.sub.2SO.sub.4, and concentrated. The residue was purified on silica gel (50% EtOAc in Hexanes) to provide the title compound as an amber oil (185.8 g, 77.5%), LRMS (M+H.sup.+) m/z 193.2.

##STR00116##

trans-3-Fluoro-1-(3-fluoropyridin-2-yl)cyclobutanecarbonitrile

[0377] To a solution of 1-(3-fluoropyridin-2-yl)-3-hydroxycyclobutanecarbonitrile (185 g, 0.96 mol) in DCM (1 L) was added DAST portion-wise at 0-10 C. Upon the completion of addition, the reaction was refluxed for 6 h. The reaction was cooled to rt and poured onto sat. NaHCO.sub.3 solution. The mixture was separated and the organic layer was washed with water, dried over Na.sub.2SO.sub.4, and concentrated. The residue was purified on silica gel (100% DCM) to provide the title compound as a brown oil (116 g, 62%) with a trans/cis ratio of 8:1 as determined by .sup.1H NMR. The above brown oil (107 g) was dissolved in a mixture of toluene (110 mL) and hexanes (330 mL) at 70 C. The solution was cooled to 0 C. and stirred at 0 C. overnight. The precipitate was filtered and washed with hexanes to provide a single trans-isomer white solid (87.3 g, 81.6%), LRMS (M+H.sup.+) m/z 195.1.

##STR00117##

trans-3-Fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methanamine

[0378] A mixture of trans-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutanecarbonitrile (71 g, 0.37 mol) and Raney nickel (7 g) in 7N ammonia in methanol (700 mL) was charged with hydrogen (60 psi) for 2 days. The reaction was filtered through a celite pad and washed with methanol. The filtrate was concentrated under high vacuum to provide the title compound as a light green oil (70 g, 98%), LRMS (M+H.sup.+) m/z 199.2.

##STR00118##

t-Butyl 6-chloropyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0379] 3-Chloro-6-fluoropyridazine (10.11 g, 76.30 mmol, 1 equiv), trans-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methanamine (15.10 g, 76.30 mmol, 4:1 trans/cis ratio), and K.sub.2CO.sub.3 (29.27 g, 304.9 mmol) in CH.sub.3CN (20 mL) were refluxed overnight. Upon cooling, water was added into the mixture. The precipitate was collected and dried to give 9.2 g (39%) of desired product with ratio of trans:cis greater than 20:1. To this solid (9.2 g) and DMAP (353 mg, 2.9 mmol) in THF (100 mL) was added (Boc).sub.2O (12.8 g, 58.7 mmol). The mixture was then refluxed for 2 h, cooled, and concentrated. The residue was purified on silica gel to provide the title compound as a white solid (9 g, 75%), LRMS (M+H.sup.+) m/z 411.2.

##STR00119##

Methyl 3-(6-(t-butoxycarbonyl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-fluorobenzoate

[0380] To t-butyl 6-chloropyridazin-3-yl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (30.3 g, 73.9 mmol, 1 equiv), 2-fluoro-5-(methoxycarbonyl)phenylboronic acid (16.1 g, 81.3 mmol, 1.1 equiv), (dppf)PdCl.sub.2 (6.0 g, 7.39 mmol, 0.1 equiv), K.sub.2CO.sub.3 (40.8 g, 296 mmol, 4 equiv) were added dioxane (160 mL) and water (40 mL). The mixture was heated 2 h at 80 C., cooled and diluted with EtOAc. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered, and concentrated. The residue was purified on silica gel to provide the title compound as pale orange solid (29.4 g, 75%), LRMS (M+H.sup.+) m/z 529.2.

##STR00120##

3-(6-(t-butoxycarbonyl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-fluorobenzoic acid

[0381] To a 500 mL round bottom flask was added methyl 3-(6-(t-butoxycarbonyl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-fluorobenzoate (29.4 g, 55.7 mmol, 1 equiv), THF (200 mL), MeOH (100 mL), and NaOH (74.2 mL of a 3N aqueous solution, 222 mmol). The mixture was heated 30 min at 60 C., cooled, acidified to pH 3 with NaHSO.sub.4 (1N), and concentrated. The residue was partitioned between EtOAc and water. The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered, and concentrated to provide the title compound as a pale orange solid (29 g, crude), LRMS (M+H.sup.+) m/z 515.2.

##STR00121##

t-Butyl ((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(2-fluoro-5-(methylcarbamoyl)phenyl)pyridazin-3-yl)carbamate

[0382] To 3-(6-(t-butoxycarbonyl(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)amino)pyridazin-3-yl)-4-fluorobenzoic acid (29 g, 55.7 mmol, 1 equiv) in DCM (200 mL) was added oxalyl chloride (19.4 mL, 222 mmol, 4 equiv). The reaction was stirred for 1 h, concentrated, and azeotroped twice with toluene. The crude product was then dissolved in DCM and cooled to 0 C. To this mixture was added NH.sub.2Me (2M/THF, 278 mL, 556.8 mmol). The mixture was warmed to rt and stirred at rt for 30 min. The solid was filtered off and the filtrate was concentrated. The crude product was purified on silica gel to provide the title compound as pale yellow solid (28.1 g, 96%), LRMS (M+H.sup.+) m/z 528.2.

##STR00122##

4-fluoro-3-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)-N-methylbenzamide

[0383] To tert-butyl ((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(2-fluoro-5-(methylcarbamoyl)phenyl)pyridazin-3-yl)carbamate (28.1 g, 53.3 mmol) in DCM (100 mL) was added TFA (40 mL, 533 mmol, 10 equiv) at rt. The reaction mixture was further stirred at rt for 2 h followed by concentration to dryness. The residue was partitioned between EtOAc and NaHCO.sub.3. The pH was further adjusted to pH 9 with NaOH (1N). The organic layer was washed with brine, dried over Na.sub.2SO.sub.4, filtered, and concentrated to give 25.2 g of a pale yellow solid. The solid was dissolved in EtOH (80 mL), warmed to 66 C. and diluted with water (80 mL) at 66 C. The mixture was slowly cooled to rt with stirring. The precipitate was filtered, washed with water, and dried to provide the title compound as a white solid (21.2 g, 93%), LRMS (M+H.sup.+) m/z 428.2.

EXAMPLE 36: PREPARATION OF 6-(5-(1H-PYRAZOL-3-YL)THIAZOL-2-YL)-N-((1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYL)PYRIDAZIN-3-AMINE

[0384] ##STR00123##

t-Butyl 6-(5-bromothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate

[0385] To a 100 mL round bottom flask was added t-butyl (1-(3-fluoropyridin-2-yl)cyclobutyl)methyl(6-(thiazol-2-yl)pyridazin-3-yl)carbamate (2.0 g, 4.6 mmol), NBS (1.6 g, 9.1 mmol), and DMF (20 mL). The reaction was heated to 100 C. and stirred overnight. The reaction mixture was then was poured into ethyl acetate (200 mL), washed with water (100 mL), dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography (EtOAc/hex) to afford 1.8 g of t-butyl 6-(5-bromothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate.

##STR00124##

6-(5-(1H-pyrazol-3-yl)thiazol-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine

[0386] To a microwave vial was added t-butyl 6-(5-bromothiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate (100 mg, 0.19 mmol), 1H-pyrazol-5-ylboronic acid (32 mg, 0.29 mmol), (dppf)PdCl.sub.2 (16 mg, 0.02 mmol), dioxane (2 mL), and K.sub.2CO.sub.3 (0.2 mL of a 2M aqueous solution, 38 mmol). The mixture was heated to 140 C. in a microwave reactor and stirred for 20 min. The reaction mixture was then poured into ethyl acetate (50 mL), washed with water (20 mL), dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography (EtOAc/hex) to afford 38 mg of t-butyl 6-(5-(1H-pyrazol-3-yl)thiazol-2-yl)pyridazin-3-yl((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)carbamate. This compound was dissolved in CH.sub.2Cl.sub.2 (5 mL) and TFA (1 mL). The reaction was stirred for 30 min at rt, concentrated, and then purified using reverse phase chromatography to give 15 mg of 6-(5-(1H-pyrazol-3-yl)thiazol-2-yl)-N-((1-(3-fluoropyridin-2-yl)cyclobutyl)methyl)pyridazin-3-amine, (M+H=408.3).

EXAMPLE 37: PREPARATION OF 6-(6-((TRANS-3-FLUORO-1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)IMIDAZO[2,1-B]THIAZOLE-3-CARBOXAMIDE

[0387] ##STR00125##

2-Bromo-1-(6-chloropyridazin-3-yl)ethanone

[0388] To a stirring solution of dioxane (100 mL, degassed) was added 3,6-dichloropyridazine (5.0 g, 34 mmol), Cl.sub.2Pd(PPh.sub.3).sub.2(2.4 g, 3.4 mmol), and tributyl(l ethoxyvinyl)tin (18.2 g, 50 mmol). The reaction was heated to 100 C. and stirred for 1 h. The reaction was then concentrated, followed by the addition of EtOAc (100 mL) and potassium fluoride (50 mL of a saturated aqueous solution). The mixture was stirred for 30 min and then filtered through a pad of Celite. The filtrate was concentrated and then dissolved in THF (80 mL) and water (80 mL). NBS (18.1 g, 102 mmol) was then added, and the reaction was stirred for 20 min at rt. The reaction mixture was poured into ethyl acetate (200 mL), washed twice with brine (50 mL), dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography to afford 4.2 g of 2-bromo-1-(6-chloropyridazin-3-yl)ethanone.

##STR00126##

Ethyl 6-(6-chloropyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate

[0389] To a 20 dram vial was added 2-bromo-1-(6-chloropyridazin-3-yl)ethanone (4.2 g, 18 mmol), ethyl-2-aminothiazole-4-carboxylate (3.1 g, 18 mmol), and methylethylketone (40 mL). The mixture was heated to 90 C. and stirred overnight. The reaction was then concentrated and purified by silica gel chromatography (EtOAc/hex) to afford 1.0 g of ethyl 6-(6-chloropyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate as a yellow solid.

##STR00127##

Ethyl 6-(6-fluoropyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate

[0390] To a 20 dram vial was added ethyl 6-(6-chloropyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate (1.0 g, 3.2 mmol), 1,8-bis(dimethylamino)naphthalene (1.4 g, 6.4 mmol), and Et.sub.3N.3HF (30 mL). The reaction was heated in a microwave to 140 C. and stirred for 1.5 h. The reaction mixture was poured into ethyl acetate (100 mL), washed with water (50 mL), dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by silica gel chromatography to afford 760 mg of ethyl 6-(6-fluoropyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate as a yellow solid.

##STR00128##

Ethyl 6-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate

[0391] Ethyl 6-(6-fluoropyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate (65 mg, 0.2 mmol), (trans-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methanamine (56 mg, 0.29 mmol), DIPEA (114 L, 0.66 mmol), and NMP (3 mL). The reaction was heated to 165 C. and stirred for 2 h. The reaction was then purified directly using reverse phase chromatography to give 15 mg of ethyl 6-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate.

##STR00129##

6-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxamide

[0392] To a solution of ethyl 6-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxylate (20 mg, 0.05 mmol) in dioxane (0.5 mL) was added LiOH (1M, 0.15 mL, 0.15 mmol). The reaction mixture was stirred at rt for 1 h and then concentrated. To this crude mixture was added NH.sub.4Cl (28 mg, 0.5 mmol), HATU (28 mg, 0.075 mmol), HOAt (10 mg, 0.075 mmol), DIEA (19 mg, 0.15 mmol), and DMF (1 mL). The mixture was stirred at 50 C. for 30 min and then was purified directly by reverse phase chromatography to provide 2 mg of 6-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)imidazo[2,1-b]thiazole-3-carboxamide as a white solid, (M+H=442.1).

EXAMPLE 38: PREPARATION OF 4-FLUORO-3-(6-(((TRANS)-3-FLUORO-1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)BENZAMIDE AND 4-FLUORO-3-(6-(((CIS)-3-FLUORO-1-(3-FLUOROPYRIDIN-2-YL)CYCLOBUTYL)METHYLAMINO)PYRIDAZIN-3-YL)BENZAMIDE

[0393] ##STR00130##

[0394] To a solution of 4-fluoro-3-(6-((3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzonitrile (482 mg, 1.22 mmol, 95:5 cis/trans ratio) in DMSO (3 mL) was added potassium carbonate (673 mg, 4.88 mmol). The mixture was cooled to 0 C. and hydrogen peroxide (0.6 mL) was slowly added. The reaction was warmed to rt and stirred for 2 h. The reaction was diluted with EtOAc (75 mL) and water (50 mL), and the organic layer was washed three times with brine (50 mL). The organic layer was then dried over Na.sub.2SO.sub.4, filtered, concentrated, and purified by reverse phase chromatography to afford 470 mg of 4-fluoro-3-(6-(((trans)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzamide and 6 mg of 4-fluoro-3-(6-(((cis)-3-fluoro-1-(3-fluoropyridin-2-yl)cyclobutyl)methylamino)pyridazin-3-yl)benzamide as white solids (M+H=414.3).

EXAMPLE 39: PREPARATION AND ASSAY OF FAST SKELETAL MYOFIBRILS

[0395] Preparation of Fast Skeletal Myofibrils.

[0396] Rabbit skeletal myofibrils were prepared based upon the method of Herrmann et al. (Biochem. 32(28):7255-7263(1993). Myofibrils were prepared from rabbit psoas muscle purchased from Pel-Freez Biologicals (Arkansas) within 2 days of ordering, stored on ice. Minced muscle was homogenized in 10 volumes of ice-cold standard buffer (50 mM Tris, pH 7.4, 0.1M potassium acetate, 5 mM KCl, 2 mM DTT, 0.2 mM PMSF, 10 M leupeptin, 5 M pepstatin, and 0.5 mM sodium azide) containing 5 mM EDTA and 0.5% Triton X-100 using an Omni-Macro homogenizer. Myofibrils were recovered by low speed centrifugation (3000 rpm for 10 minutes) and washed 2 times in the Triton X-100 containing buffer to ensure removal of cellular membrane. Following the Triton washes, myofibrils were washed 3 times in standard buffer containing 2 mM magnesium acetate. A final wash in assay buffer (12 mM PIPES, pH 6.8, 60 mM KCl, 1 mM DTT) was performed and brought to 10% sucrose for flash freezing in liquid nitrogen and storage at 80 C.

[0397] Activation of Fast Skeletal Myofibrils.

[0398] Fast fiber activators were identified by measuring the enzymatic activity of muscle myofibril preparations using the proprietary PUMA (see, e.g., U.S. Pat. Nos. 6,410,254, 6,743,599, 7,202,051, and 7,378,254) assay system. Myofibril preparations consisted of rabbit skeletal muscle (approximately 90% fast fibers) that had been mechanically homogenized and washed with a detergent (triton X-100) to remove cellular membranes. This preparation retained all of the sarcomeric components in a native conformation and the enzymatic activity was still regulated by calcium. Compounds were tested using a myofibril suspension and a level of calcium sufficient to increase enzymatic activity of the myofibrils to 25% of their maximal rate (termed pCa25). Enzymatic activity was tracked via a pyruvate kinase and lactate dehydrogenase-coupled enzyme system. This assay regenerates myosin-produced ADP into ATP by oxidizing NADH, producing an absorbance change at 340 nm. The buffering system was 12 mM Pipes, 2 mM MgCl.sub.2, 1 mM DTT at pH 6.8 (PM12 buffer). Data was reported as AC1.4, which is the concentration at which the compound increased the enzymatic activity by 40%. The results are summarized in Table 2 below.

EXAMPLE 40: PREPARATION AND ASSAY OF SARCOMERIC PROTEINS FROM SKELETAL MUSCLE

[0399] Powder Preparation

1. Volumes are given per about 1000 g of the minced muscle.
2. Pre-cut and boil cheesecloth for 10 min in water. Drain and dry.
3. Mince chicken breast in a prechilled meat grinder.
4. Extract with stirring in 2 L of 0.1M KCl, 0.15M K-phosphate, pH 6.5 for 10 min at 4 C. Spin 5000 rpm, 10 min, 4 C. in JLA. Collect the pellet.
5. Extract pellets with stirring with 2 L of 0.05M NaHCO.sub.3 for 5 min. Spin 5000 rpm, 10 min, 4 C. in JLA. Collect the pellet. Repeat the extraction once more.
6. Extract the filtered residue with 2 L of 1 mM EDTA, pH 7.0 for 10 min with stirring.
7. Extract with 2 L of H.sub.2O for 5 min with stirring. Spin 10000 rpm, 15 min, 4 C. in JLA. Carefully collect the pellet, part of which will be loose and gelatinous.
8. Extract 5 times with acetone (2 L of acetone for 10 min each with stirring). Squeeze through cheesecloth gently. All acetone extractions are performed at room temperature. Acetone should be prechilled to 4 C.
9. Drying: Place the filtered residue spread on a cheesecloth in a large glass tray and leave in a hood overnight. When the residue is dry, put in a wide mouth plastic bottle and store at 20 C.

[0400] Alternate Powder Preparation

(See Zot & Potter (1981) Prep. Biochem. 11(4) pp. 381-395)
1. Dissect left ventricles of the cardiac muscle. Remove as much of the pericardial tissue and fat as possible. Grind in a prechilled meat grinder. Weigh.
2. Prepare 5 volumes of Extract buffer (see below). Homogenize the meat in a blender, 4 times 15 sec on blend with 15 secs in between. Do this with 1 volume (weight/volume) of buffer taken from the 5 volumes already prepared. Add the homogenate back to the extract buffer and stir until well mixed (5 minutes).
3. Filter through one layer of cheesecloth in large polypropylene strainer. Resuspend back into 5 volumes of extract buffer as above.
4. Repeat Step 3 four more times. At the end, do not resuspend in extraction buffer but proceed to Step 5. The pellets should be yellow white.
5. Resuspend in 3 volumes (according to original weight) of 95% cold ethanol. Stir for 5 min and squeeze through cheesecloth as above, repeat two more times.
6. Weigh squeezed residue and then resuspend in 3 volumes (new weight/volume) of cold diethyl ether.
7. Repeat Step 6 a total of three times.
8. Leave overnight in a single layer on a cheesecloth in a glass tray.
9. When dry, collect the powder, weigh and store in a wide-mouth jar at 4 C.
EXTRACT BUFFER: 50 mM KCl, 5 mM Tris pH 8.0 Prepare as 50 times concentrate. For 2 L: 250 mM Tris pH 8.0. Tris Base (121.14 g/mol, 60.6 g), pH to 8.0 with conc. HCl, then add 2.5M KCl (74.55 g/mol, 372 g).

[0401] Actin Preparation

1. Extract powder (as described above) with 20 ml buffer A (see below, add BME and ATP just prior to use in each of the following steps) per gram of powder (200 ml per 10 g). Use a large 4 L beaker for 150 g of powder. Mix vigorously to dissolve powder. Stir at 4 C. for 30 min.
2. Separate extract from the hydrated powder by squeezing through several layers of cheesecloth. Cheesecloth should be pre-sterilized by microwaving damp for 1-2 min.
3. Re-extract the residue with the same volume of buffer A and combine extracts.
4. Spin in JLA10 rotor(s) for 1 hr at 10K rpm (4 C.). Collect supernatant through 2 layers of cheesecloth.
5. Add ATP to 0.2 mM and MgCl.sub.2 to 50 mM. Stir on stir plate at 4 C. for 60 minutes to allow actin to polymerize/form para-crystals.
6. Slowly add solid KCl to 0.6M (45 g/l). Stir at 4 C. for 30 min.
7. Spin in JLA10 rotor(s) at 10K rpm for 1 hr.
8. Depolymerization: Quickly rinse surface of pellets with buffer A and dispose of wash. Soften the pellets by pre-incubation on ice with small amount of buffer A in each tube (use less than half of final resuspension volume total in all tubes). Resuspend by hand first with cell scraper and combine pellets. Wash tubes with extra buffer using a 25 ml pipette and motorized pipettor, aggressively removing actin from sides of tubes. Homogenize in large dounce in cold buffer A on ice. Use 3 ml per gram of powder originally extracted.
9. Dialyze against buffer A with 4 changes over 48 hour period.
10. Collect dialyzed actin and spin in the 45Ti rotor at 40K rpm for 1.5 hr (4 C.).
11. Collect supernatant (G-Actin). Save a sample for gel analysis and determination of protein concentration.
12. To polymerize G-actin for storage, add KCl to 50 mM (from 3M stock), MgCl.sub.2 to 1 mM, and NaN.sub.3 to 0.02% (from 10% stock). Store at 4 C. Do not freeze.
Buffer A: 2 mM tris/HCl, 0.2 mM CaCl.sub.2, 0.5 mM (36 l/L) 2-mercaptoethanol, 0.2 mM Na.sub.2 ATP (added fresh), and 0.005% Na-azide; pH 8.0.

[0402] Purification of Skeletal Muscle Myosin

(See Margossian, S. S. and Lowey, S. (1982) Methods Enzymol. 85, 55-123; and Goldmann, W. H. and Geeves, M. A. (1991) Anal. Biochem. 192, 55-58) Solution A: 0.3M KCl, 0.15M potassium phosphate, 0.02M EDTA, 0.005M MgCl.sub.2, 0.001M ATP, pH 6.5.
Solution B: 1M KCl, 0.025M EDTA, 0.06M potassium phosphate, pH 6.5.
Solution C: 0.6M KCl, 0.025M potassium phosphate, pH 6.5.
Solution D: 0.6M KCl, 0.05M potassium phosphate, pH 6.5.
Solution E: 0.15M potassium phosphate, 0.01M EDTA, pH 7.5.
Solution F: 0.04M KCl, 0.01M potassium phosphate, 0.001M DTT, pH 6.5.
Solution G: 3M KCl, 0.01M potassium phosphate, pH 6.5.
All procedures are carried out at 4 C.
1. Obtain approx. 1000 g skeletal muscle, such as rabbit skeletal muscle.
2. Grind twice; extract with 2 L solution A for 15 min while stirring; add 4 L cold H.sub.2O, filter through gauze; dilute with cold H.sub.2O to ionic strength of 0.04, (about 10-fold); let settle for 3 h; collect precipitate at 7,000 rpm in GSA rotor for 15 min.
3. Disperse pellet in 220 ml solution B; dialyze overnight against 6 L solution C; slowly add 400 ml equal volume cold distilled H.sub.2O; stir for 30 min; centrifuge at 10,000 rpm for 10 min in GSA rotor.
4. Centrifuge supernatant at 19,000 rpm for 1 h.
5. Dilute supernatant to ionic strength of 0.04 (8-fold); let myosin settle overnight; collect about 5-6 L fluffy myosin precipitate by centrifuging at 10,000 rpm for 10 min in GSA rotor.
6. Resuspend pellet in minimal volume of solution G; dialyze overnight against 2 L solution D; centrifuge at 19,000 rpm for 2 h, in cellulose nitrate tubes; puncture tubes and separate myosin from fat and insoluble pellet.
7. Dilute supernatant to 5-10 mg/ml and dialyze against solution E extensively, load onto DEAE-sephadex column.
8. Pre-equilibrate with solution E; apply 500-600 g myosin at 30 ml/h; wash with 350 ml solution E; elute with linear gradient of 0-0.5M KCl in solution E (21 liter); collect 10 ml fractions; pool myosin fractions (>0.1M KCl); concentrate by overnight dialysis against solution F; centrifuge at 25,000 rpm for 30 min; store as above.
9. The myosin is then cut with chymotrypsin or papain in the presence of EDTA to generate the S1 fragment which is soluble at the low salt conditions optimal for ATPase activity (Margossian, supra).

[0403] Preparation and Assay

[0404] Myosin is prepared by precipitation from salt extracts of rabbit psoas muscle, and a soluble S1 fraction is prepared by digestion with chymotrypsin (Margossian and Lowey, 1982).

[0405] Actin is purified by first preparing an ether powder of cardiac muscle (Zot H G and Potter J D. (1981) Preparative Biochemistry 11:381-395) as described above. Subsequently, actin is cycled between the filamentous and soluble state through rounds of centrifugation and dialysis (Spudich J A and Watt S. (1971) J. Biol. Chem. 246:4866-4871).

[0406] Tropomyosin is extracted from the ether powder and separated from the other proteins based on pH dependent precipitations followed by successive ammonium sulfate cuts at 53% and 65% (Smillie L B. (1981) Methods Enzymol 85 Pt B:234-41). The troponins are isolated as an intact complex of TnC, TnT, and TnI. Ether powder is extracted in a high salt buffer. Successive ammonium sulfate cuts of 30% and 45% are done; the precipitate is solubilized by dialysis into a low salt buffer and then further purified on a DEAE Toyopearl column with a 25-350 mM KCl gradient. There is no measurable ATPase in any of the components except for myosin which naturally had a very low basal ATPase in the absence of actin.

[0407] Prior to screening, the actin, tropomyosin, and troponin complex are mixed together in the desired ratio (e.g., 7:1:1) to achieve maximal calcium regulation of the actin filament. The screen is conducted at a concentration that gives 25% activation. This calcium concentration is in the physiological range during muscle contraction.

[0408] To measure the generation of ADP during the reaction, a pyruvate kinase/lactate dehydrogenase/NADH coupled enzyme system (PK/LDH) is added to the actin. The myosin is kept separately, and added to the regulated thin filaments to initiate the reaction. Oxidation of NADH is monitored in real time, so that kinetic curves are obtained. Compounds are dissolved in DMSO and spotted onto the bottoms of 384 well plates at 10 to 40 g/ml final concentration.

[0409] Using procedures similar to those described herein, utilizing reagents and intermediates commercially available (e.g., Sigma-Aldrich, St. Louis, Mo.) or readily synthesized by one of skill in the art, the compounds in Table 2 were synthesized, characterized and tested. AC1.4 values were determined according to the procedure described in Example 39, and the reported median AC1.4 values are as follows: A=<1 uM; B=1-10 uM; C=10-20 uM; D=>20 uM.

TABLE-US-00002 TABLE 2 m/z Mean Compound Structure (M + H) AC1.4 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00131] 365.2 A 4-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00132] 365.1 B 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-3-carbonitrile [00133] 348.1 B methyl 5-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-3-carboxylate [00134] 381.1 B 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-3-carboxamide [00135] 366.1 B [2-(4-fluorophenyl)-2- methylpropyl](6-pyrazol-4- ylpyridazin-3-yl)amine [00136] 312.1 B [2-(4-fluorophenyl)-2- methylpropyl](6-prop-2- enylpyridazin-3-yl)amine [00137] 281.6 B [6-((1E)prop-1-enyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00138] 286.1 B 3-(6-{[(2S)-2-(4- fluorophenyl)propyl]amino}pyr- idazin-3-yl)benzamide [00139] 351.0 B 3-(6-{[(2R)-2-(4- fluorophenyl)propyl]amino}pyr- idazin-3-yl)benzamide [00140] 351.0 B 3-(6-{[2-(4- chlorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00141] 353.1 D 3-(6-{[2-(3- chlorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00142] 353.1 B 3-(6-{[2-(2- chlorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00143] 353.1 B 3-(6-{[2-(4- methylphenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00144] 333.2 C 3-(6-{[2-(4- fluorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00145] 337.1 D 3-(6-{[2-(4- methoxyphenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00146] 349.1 D (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyr- idazin-3-yl)methan-1-ol [00147] 276.1 D methyl 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazine- 3-carboxylate [00148] 304.2 C 3-(6-{[2-(2,4- dichlorophenyl)ethyl]amino}pyr- idazin-3-yl)benzenecarbonitrile [00149] 369.0 D 3-(6-{[2-(2,4- dichlorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00150] 387.0 C 3-(6-{[2-(3,4- dichlorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00151] 387.0 C 3-(6-{[2-(2,4- difluorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00152] 355.1 D 3-(6-{[2-(3,4- difluorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00153] 355.1 C 3-(6-{[2-(3,5- difluorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00154] 355.1 D 3-{6-[(2-(4- pyridyl)ethyl)amino]pyridazin- 3-yl}benzamide [00155] 320.1 D 3-{6-[(2-(3- pyridyl)ethyl)amino]pyridazin- 3-yl}benzamide [00156] 320.1 D 3-{6-[(2-(2- pyridyl)ethyl)amino]pyridazin- 3-yl}benzamide [00157] 320.1 D 3-{6-[(2- phenylethyl)amino]pyridazin- 3-yl}benzamide [00158] 319.1 D 3-{6-[(3- methylbutyl)amino]pyridazin-3- yl}benzamide [00159] 319.1 D 3-{6-[(2- phenylpropyl)amino]pyridazin- 3-yl}benzamide [00160] 333.1 B 3-(6-{[(4- fluorophenyl)ethyl]amino}pyr- idazin-3-yl)benzamide [00161] 337.1 C 3-{6- [(phenylethyl)amino]pyridazin- 3-yl}benzamide [00162] 319.1 D 3-{6-[(3,3- dimethylbutyl)amino]pyridazin- 3-yl}benzamide [00163] 299.2 D 3-{6-[(2-pyrazin-2- ylethyl)amino]pyridazin-3- yl}benzamide [00164] 321.1 D 3-(6-{[2-(2-chlorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00165] 381.1 A 3-(6-{[2-(4-chlorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00166] 381.1 B 3-(6-{[2-(2,4-difluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00167] 383.1 B 3-[6-({[(4- fluorophenyl)cyclopropyl]meth- yl}amino)pyridazin-3- yl]benzamide [00168] 362.2 A (6-(1H-indazol-6-yl)pyridazin- 3-yl)[2-(4-fluorophenyl)-2- methylpropyl]amine [00169] 362.1 A 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzenecarbonitrile [00170] 347.1 B (6-(1H-indazol-5-yl)pyridazin- 3-yl)[2-(4-fluorophenyl)-2- methylpropyl]amine [00171] 362.2 A 3-(6-{[2-(2-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00172] 365.1 A (6-(1H-indazol-4-yl)pyridazin- 3-yl)[2-(4-fluorophenyl)-2- methylpropyl]amine [00173] 362.1 A 5-[6-({[(4- fluorophenyl)cyclopropyl]meth- yl}amino)pyridazin-3- yl]pyridine-3-carboxamide [00174] 364.1 B 5-[6-({[(4- fluorophenyl)cyclopropyl]meth- yl}amino)pyridazin-3- yl]pyridine-3-carbonitrile [00175] 346.1 B 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazine- 3-carbonitrile [00176] 271.1 D 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazine- 3-carboxamide [00177] 289.1 C 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)-3-hydrobenzimidazol-2-one [00178] 378.1 A 3-(6-{[2-(3-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00179] 365.1 A (6-(1H-1,2,3,4-tetraazol-5- yl)pyridazin-3-yl)[2-(4- fluorophenyl)-2- methylpropyl]amine [00180] 314.1 D 5-(6-{[2-(2-chlorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-3-carboxamide [00181] 382.1 B 5-(6-{[2-(2-chlorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-3-carbonitrile [00182] 364.1 B [(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)methyl](methylsulfonyl)amine [00183] 353.1 B N-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)methyl]methoxycarboxamide [00184] 333.2 D [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00185] 377.1 A [6-(3-amino(1H-indazol-7- yl))pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00186] 377.0 B [6-(3-aminobenzo[3,4-d]isoxazol- 5-yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00187] 378.0 B [6-(3-aminobenzo[d]isoxazol-7- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00188] 388.0 B [2-(2-chlorophenyl)-2- methylpropyl](6-(3- pyridyl)pyridazin-3-yl)amine [00189] 339.1 B [2-(2-chlorophenyl)-2- methylpropyl](6-pyrimidin-5- ylpyridazin-3-yl)amine [00190] 340.1 B 3-[6-({[(2- chlorophenyl)cyclopropyl]meth- yl}amino)pyridazin-3- yl]benzamide [00191] 379.1 A 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}-5- methylpyridazin-3- yl)benzenecarbonitrile [00192] 361.1 C 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}-5- methylpyridazin-3-yl)benzamide [00193] 379.1 B 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}-4- methylpyridazin-3- yl)benzenecarbonitrile [00194] 361.1 B 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}-4- methylpyridazin-3-yl)benzamide [00195] 379.1 B [3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl]-N-(2- hydroxyethyl)carboxamide [00196] 409.1 B N-(2,3-dihydroxypropyl)[3-(6- {[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl]carboxamide [00197] 439.1 B 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl piperidyl ketone [00198] 433.2 B 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl morpholin-4-yl ketone [00199] 435.1 B N-(2-aminoethyl)[3-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl]carboxamide [00200] 408.2 A [3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl]-N-(2-{[3-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl]carbonylamino}eth- yl)carboxamide [00201] 755.3 B tert-butyl 4-{[3-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl]carbonyl}piperazine- carboxylate [00202] 534.2 B 2-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00203] 365.0 B 5-[6-({[(4- fluorophenyl)cyclopropyl]meth- yl}amino)pyridazin-3-yl]-3- hydrobenzimidazol-2-one [00204] 376.1 A [2-(4-fluorophenyl)-2- methylpropyl][6-(1-methyl(1H- indazol-6-yl))pyridazin-3- yl]amine [00205] 376.2 B 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)phenyl piperazinyl ketone [00206] 434.2 B 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)carbonyl]pyrrolidine-2- carboxamide [00207] 386.1 D ethyl 1-[(6-{[2-(4-fluorophenyl)- 2-methylpropyl]amino}pyridazin- 3-yl)carbonylamino]cyclopropane- carboxylate [00208] 401.1 D 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazine- 3-carboxylic acid [00209] 290.1 D 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonylamino]cyclopropane- carboxylic acid [00210] 373.1 D 3-(6-{[2-(2- chlorophenyl)pentyl]amino}pyr- idazin-3-yl)benzamide [00211] 395.1 B [6-(3-amino-1-methyl(1H-indazol- 5-yl))pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00212] 391.0 B 3-(6-{[2-(2-fluorophenyl)-4- methoxybutyl]amino}pyridazin- 3-yl)benzamide [00213] 395.1 D 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl morpholin-4-yl ketone [00214] 359.1 D 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl 4-methylpiperazinyl ketone [00215] 372.1 D tert-butyl 4-[(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]piperazinecarboxylate [00216] 458.2 D tert-butyl 4-[(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]-3- (hydroxymethyl)piperazinecar- boxylate [00217] 488.2 D 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]azetidine-2- carboxamide [00218] 372.1 D 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]piperidine-2- carboxamide [00219] 400.1 D 4-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)carbonyl]piperazin-2-one [00220] 372.1 D 5-(6-{[2-(2-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-3-hydrobenzimidazol-2-one [00221] 378.2 A [6-(3-amino(1H-indazol-6- yl))pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00222] 377.0 A [6-(3-aminobenzo[d]isoxazol-6- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00223] 378.0 A 3-fluoro-5-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00224] 383.1 B N-(1-carbamoyl-3- methylbutyl)(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carboxamide [00225] 402.2 C N-((1S)-1-carbamoyl-2- hydroxyethyl)(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carboxamide [00226] 376.1 D (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-N-(pyrazol-3- ylmethyl)carboxamide [00227] 369.1 C 3-(5-cyano-6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00228] 390.2 C 6-(3-carbamoylphenyl)-3-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazine- 4-carboxamide [00229] 408.2 B 5-[6-({2-[2- (hydroxymethyl)phenyl]-2- methylpropyl}amino)pyridazin-3- yl]-3-hydrobenzimidazol-2-one [00230] 390.1 B 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]piperidine-3- carboxamide [00231] 400.1 D (2S,1R)-2-[(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonylamino]cyclopentane- carboxamide [00232] 400.1 D N-(2-carbamoylethyl)(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carboxamide [00233] 360.1 D 4-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]piperazine-2- carboxamide [00234] 401.1 D 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]pyrrolidine-3- carboxamide [00235] 386.1 D 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonylamino]cyclopropane- carboxamide [00236] 372.1 D 5-{6-[(2,2- dimethylpropyl)amino]pyridazin- 3-yl}-3-hydrobenzimidazol-2-one [00237] 298.2 D 3-(6-{[3-(1,3-dioxolan-2-yl)-2-(2- fluorophenyl)propyl]amino}pyr- idazin-3-yl)benzamide [00238] 423.1 D 6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl piperazinyl ketone [00239] 358.0 D 4-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]piperazinecarbox- amide [00240] 401.0 D 5-{6-[(2-methyl-2- phenylpropyl)amino]pyridazin-3- yl}-3-hydrobenzimidazol-2-one [00241] 360.1 A 5-(6-{[2-(4-fluorophenyl)-tert- butyl]amino}pyridazin-3-yl)-3- hydrobenzimidazol-2-one [00242] 378.1 D (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-N-pyrazol-5-ylcarboxamide [00243] 355.1 D (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-N-(2-oxo(3- piperidyl))carboxamide [00244] 386.1 D 4-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonylamino]piperidinecar- boxamide [00245] 401.1 D (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-N-[(5-oxopyrrolidin-2- yl)methyl]carboxamide [00246] 386.2 C 3-(6-{[2-(2-fluoro- phenyl)butyl]amino}pyridazin-3- yl)benzamide [00247] 365.1 B (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-N-(2-oxopyrrolidin-3- yl)carboxamide [00248] 372.1 C N-{3-[(tert- butoxy)carbonylamino]propyl}[3- (6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl]carboxamide [00249] 522.2 B N-(3-aminopropyl)[3-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl]carboxamide [00250] 422.2 B (6-benzimidazol-5-ylpyridazin-3- yl)[2-(4-fluorophenyl)-2- methylpropyl]amine [00251] 362.2 A [2-(4-fluorophenyl)-2- methylpropyl][6-(2- methylbenzimidazol-5- yl)pyridazin-3-yl]amine [00252] 376.2 B [6-(2-aminobenzimidazol-5- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00253] 377.2 A [3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl]-N-methylcarboxamide [00254] 379.1 B 3-(6-{[2-(2- oxopyrrolidinyl)propyl]ami- no}pyridazin-3-yl)benzamide [00255] 340.1 D 3-(6-{[2-(2- oxopiperidyl)propyl]amino}pyr- idazin-3-yl)benzamide [00256] 354.1 D N-[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-2-pyridyl]acetamide [00257] 380.2 B [2-(4-fluorophenyl)-2- methylpropyl][6-(2- methylbenzoxazol-5-yl)pyridazin- 3-yl]amine [00258] 377.2 B [2-(4-fluorophenyl)-2- methylpropyl][6-(2- methylbenzoxazol-6-yl)pyridazin- 3-yl]amine [00259] 377.2 B 1-[(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carbonyl]piperidine-4- carboxamide [00260] 400.2 D N-((1S)-1-carbamoyl-2- phenylethyl)(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carboxamide [00261] 436.1 C N-((1R)-1-carbamoyl-2- phenylethyl)(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carboxamide [00262] 436.1 C N-(carbamoylmethyl)(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)carboxamide [00263] 346.1 D N-(1,3-dicarbamoylpropyl)(6-{[2- (4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)carboxamide [00264] 417.1 D 3-(6-{[2-(2- fluorophenyl)propyl]amino}pyr- idazin-3-yl)benzamide [00265] 351.1 B 3-(6-{[2-(3-fluoro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)benzamide [00266] 366.1 B 3-(6-{[2-(5-fluoro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)benzamide [00267] 366.1 C 3-[6-(3,3- dimethylindolinyl)pyridazin-3- yl]benzamide [00268] 345.2 D 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-3-hydrobenzoxazol-2-one [00269] 379.2 A 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl phenyl ketone [00270] 426.2 D 4-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl phenyl ketone [00271] 426.2 D [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(4- fluorophenyl)cyclopropyl]meth- yl}amine [00272] 375.3 A [2-(4-fluorophenyl)-2- methylpropyl][6-(3-iodo(1H- indazol-5-yl))pyridazin-3- yl]amine [00273] 488.0 B [2-(4-fluorophenyl)-2- methylpropyl](6-(4-1,2,5,6- tetrahydropyridyl)pyridazin-3- yl)amine [00274] 327.2 B [2-(4-fluorophenyl)-2- methylpropyl](6-pyrazol-3- ylpyridazin-3-yl)amine [00275] 312.1 B 1-acetyl-4-(6-{[2-(4-fluorophenyl)- 2-methylpropyl]amino}pyridazin- 3-yl)-1,2,5,6-tetrahydropyridine [00276] 369.1 D methyl 4-(6-{[2-(4-fluorophenyl)- 2-methylpropyl]amino}pyridazin- 3-yl)-1,2,5,6- tetrahydropyridinecarboxylate [00277] 385.1 C 4-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1-(methylsulfonyl)-1,2,5,6- tetrahydropyridine [00278] 405.1 B 4-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1,2,5,6- tetrahydropyridinecarboxamide [00279] 370.1 B 3-{6-[(2- piperidylpropyl)amino]pyridazin- 3-yl}benzamide [00280] 340.1 D [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl](2- piperidylpropyl)amine [00281] 352.2 D 3-{6-[(1,2,3,4- tetrahydronaphthylmethyl)ami- no]pyridazin-3-yl}benzamide [00282] 359.0 B (tert-butoxy)-N-(2-{[5-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)(1H-indazol-3- yl)]amino}ethyl)carboxamide [00283] 520.2 A [2-(4-fluorophenyl)-2- methylpropyl](6- pyrrolo[3,2-b]pyridin-6- ylpyridazin-3-yl)amine [00284] 362.2 A [2-(4-fluorophenyl)-2- methylpropyl](6- pyrazolo[5,4-b]pyridin-5- ylpyridazin-3-yl)amine [00285] 363.2 B 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-3-hydrobenzoxazol-2-one [00286] 379.2 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(2- fluorophenyl)cyclopropyl]meth- yl}amine [00287] 375.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(2- fluorophenyl)cyclobutyl]meth- yl}amine [00288] 389.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2,2-difluoro-2- (4-fluorophenyl)ethyl]amine [00289] 385.0 B 3-[6-(indan-2-ylamino)pyridazin- 3-yl]benzamide [00290] 331.0 D 3-{6- [(indanylmethyl)amino]pyridazin- 3-yl}benzamide [00291] 345.0 B (6-{3-[(2-aminoethyl)amino](1H- indazol-5-yl)}pyridazin-3-yl)[2-(4- fluorophenyl)-2- methylpropyl]amine [00292] 420.1 A 1-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)ethan-1-one [00293] 288.1 D 4-fluoro-3-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzamide [00294] 283.1 A 3-{6-[((2S,1R)-2- phenylcyclopropyl)amino]pyr- idazin-3-yl}benzamide [00295] 331.0 D [2-(4-fluorophenyl)-2- methylpropyl][6-(3-methyl(1H- indazol-6-yl))pyridazin-3- yl]amine [00296] 376.0 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(4- fluorophenyl)cyclobutyl]meth- yl}amine [00297] 389.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(2- fluorophenyl)cyclopentyl]meth- yl}amine [00298] 403.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-methyl-2- (2-methylphenyl)propyl]amine [00299] 373.2 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(4- fluorophenyl)cyclohexyl]meth- yl}amine [00300] 417.2 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3- yl][(phenylcyclopropyl)methyl]a- mine [00301] 357.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3- yl][(phenylcyclobutyl)methyl]a- mine [00302] 371.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][(2,2-dimethyl- 1-phenylcyclopropyl)methyl]a- mine [00303] 385.2 A 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazole-3-carbonitrile [00304] 387.1 D [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(4- fluorophenyl)cyclopentyl]meth- yl}amine [00305] 403.1 A 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazole-3-carboxamide [00306] 405.1 A [4-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]methan-1-ol [00307] 389.2 D {[4-(2-{[6-(3-amino(1H-indazol- 5-yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]methyl}dimethyl- amine [00308] 416.2 D [2-(4-fluorophenyl)-2- methylpropyl][6-(3-vinyl(1H- indazol-5-yl))pyridazin-3- yl]amine [00309] 388.1 A [6-(3-ethyl(1H-indazol-5- yl))pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00310] 390.2 B 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1,2,4-oxadiazole-5- carboxamide [00311] 357.1 C [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-(3-fluoro(2- pyridyl))-2-methylpropyl]amine [00312] 378.1 B [6-(3-amino(1H-indazol-6- yl))pyridazin-3-yl][2-(3-fluoro(2- pyridyl))-2-methylpropyl]amine [00313] 378.1 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-(5-fluoro(2- pyridyl))-2-methylpropyl]amine [00314] 378.1 B [6-(3-amino(1H-indazol-6- yl))pyridazin-3-yl][2-(5-fluoro(2- pyridyl))-2-methylpropyl]amine [00315] 378.1 C 1-[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)-1H-indazol-3-yl]ethane- 1,2-diol [00316] 422.1 B 2-amino-6-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)-3-hydropyrimidin-4-one [00317] 355.1 B N-[6-(2-amino-6- oxohydropyrimidin-4- yl)pyridazin-3-yl](tert- butoxy)-N-[2-(4-fluorophenyl)-2- methylpropyl]carboxamide [00318] 455.1 B 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-3-hydroquinazolin-4-one [00319] 390.1 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl](2-methyl-2- (1,3-oxazol-2-yl)propyl)amine [00320] 350.3 D ethyl 2-fluoro-5-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)benzoate [00321] 412.2 B 2-amino-6-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)-3-hydroquinazolin-4-one [00322] 405.1 A 4-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)benzenecarbonitrile [00323] 384.1 A 4-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)benzamide [00324] 402.2 D [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{2-[4- (aminomethyl)phenyl]-2- methylpropyl}amine [00325] 388.2 D 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazole-3-carboxamidine [00326] 404.1 B 2-[4-(2-{[6-(3-amino(1H-indazol- 5-yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]propan-2-ol [00327] 417.2 D [3-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]methan-1-ol [00328] 389.2 B 2-[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazol-3-yl]propan-2-ol [00329] 420.1 B 3-(6-{[2-(3,5-difluoro(2-pyridyl))- 2-methylpropyl]amino}pyridazin- 3-yl)benzamide [00330] 384.0 B [5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazol-3-yl]methan-1-ol [00331] 392.1 A {[3-(2-{[6-(3-amino(1H-indazol- 5-yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]methyl}dimethyl- amine [00332] 416.3 D 3-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)benzenecarbonitrile [00333] 384.2 A 3-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)benzamide [00334] 402.2 D 2-[3-(2-{[6-(3-amino(1H-indazol- 5-yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]propan-2-ol [00335] 417.2 C [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-(3,5- difluoro(2-pyridyl))-2- methylpropyl]amine [00336] 396.0 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00337] 390.0 A 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00338] 378.2 A N-[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazol-3-yl]acetamide [00339] 419.1 A [6-(3- aminopyrazolo[5,4-b]pyridin-5- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00340] 387.3 A [3-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]-N- methylcarboxamide [00341] 416.2 D [3-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]-N,N- dimethylcarboxamide [00342] 430.2 C [5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)(1H-indazol-3- yl)](methylsulfonyl)amine [00343] 455.1 A [2-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]methan-1-ol [00344] 389.1 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{2-[3- (aminomethyl)phenyl]-2- methylpropyl}amine [00345] 388.2 C {[(4- fluorophenyl)cyclobutyl]meth- yl}[6-(2-methoxypyrimidin-5- yl)pyridazin-3-yl]amine [00346] 366.1 B 5-[6-({[(4- fluorophenyl)cyclobutyl]meth- yl}amino)pyridazin-3-yl]-3- hydropyrimidin-2-one [00347] 352.1 B 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazole-7-carboxamide [00348] 405.1 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-(3- methoxyphenyl)-2- methylpropyl]amine [00349] 389.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][2-methyl-2-(4- methylphenyl)propyl]amine [00350] 373.1 A 2-[3-(2-{[6-(3-amino(1H-indazol- 5-yl))pyridazin-3-yl]amino}-tert- butyl)phenyl]ethan-1-ol [00351] 403.2 B [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[(5-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00352] 390.0 A 3-[6-({[(5-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00353] 378.0 B (tert-butoxy)-N-[6-(2,3-dioxo(1,4- dihydroquinoxalin-6- yl))pyridazin-3-yl]-N-[2-(4- fluorophenyl)-2- methylpropyl]carboxamide [00354] 506.1 D {2-[3-(2-{[6-(3-amino(1H- indazol-5-yl))pyridazin-3- yl]amino}-tert- butyl)phenyl]ethyl}dimethyl- amine [00355] 430.2 D 3-(2-{[6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]amino}-tert- butyl)phenol [00356] 375.1 B 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1,4-dihydroquinoxaline-2,3- dione [00357] 406.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{2-[2- (methoxymethyl)phenyl]-2- methylpropyl}amine [00358] 403.2 C 3-(6-{(tert-butoxy)-N-[2-(3- fluoro(2-pyridyl))-2- methylpropyl]carbonylamino}pyr- idazin-3-yl)benzamide [00359] 466.1 D (tert-butoxy)-N-[2-(3-fluoro(2- pyridyl))-2-methylpropyl]-N-[6- (2-hydroxybenzimidazol-5- yl)pyridazin-3-yl]carboxamide [00360] 479.1 D 5-(6-{[2-(3-fluoro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)benzimidazol-2-ol [00361] 379.1 A (6-(1H-indazol-5-yl)pyridazin-3- yl)[2-(3-fluoro(2-pyridyl))-2- methylpropyl]amine [00362] 363.1 B N-[6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)benzimidazol-2-yl]acetamide [00363] 419.1 A 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1,3-dihydroquinazoline-2,4- dione [00364] 406.1 B 4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00365] 378.0 B 4-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00366] 396.2 A (6-(1H-indazol-5-yl)pyridazin-3- yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00367] 375.0 A 2-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)pyridine-4-carboxamide [00368] 366.0 A 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)pyridine-2-carboxamide [00369] 366.1 B 3-(6-{(tert-butoxy)-N-[2-(4- fluorophenyl)-2- methylpropyl]carbonylamino}pyr- idazin-3-yl)benzamide [00370] 465.3 D 3-(6-{(tert-butoxy)-N-[2-(4- fluorophenyl)-2- methylpropyl]carbonylamino}pyr- idazin-3-yl)-4-fluorobenzamide [00371] 483.3 D (6-(1H-indazol-6-yl)pyridazin-3- yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00372] 375.0 A (6-(1H-indazol-6-yl)pyridazin-3- yl){[(6-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00373] 387.1 A (6-(1H-indazol-5-yl)pyridazin-3- yl){[(6-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00374] 387.1 A 4-fluoro-3-[6-({[(6-methoxy(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00375] 408.1 A 4-fluoro-3-(6-{[(2- pyridylcyclobutyl)methyl]ami- no}pyridazin-3-yl)benzamide [00376] 378.1 A (6-(1H-indazol-5-yl)pyridazin-3- yl)[(2- pyridylcyclobutyl)methyl]amine [00377] 357.2 A (6-(1H-indazol-6-yl)pyridazin-3- yl)[(2- pyridylcyclobutyl)methyl]amine [00378] 357.2 A 2-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00379] 396.0 B 3-fluoro-4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00380] 396.0 B 2-fluoro-4-(6-{[2-(4-fluorophenyl)- 2-methylpropyl]amino}pyridazin- 3-yl)benzoic acid [00381] 384.1 D methyl 3-amino-5-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazolecarboxylate [00382] 435.1 B methyl 5-(6-{[2-(4-fluorophenyl)- 2-methylpropyl]amino}pyridazin- 3-yl)-3-(methoxycarbonylamino)- 1H-indazolecarboxylate [00383] 493.1 C N-[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)(1H-indazol-3- yl)]methoxycarboxamide [00384] 435.1 A [3-amino-5-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)(1H-indazolyl)]-N,N- dimethylcarboxamide [00385] 448.1 B 6-({[(6-(1H-indazol-5- yl)pyridazin-3- yl)amino]methyl}cyclobutyl) pyridin-2-ol [00386] 373.1 D 6-({[(6-(1H-indazol-6-yl)pyridazin- 3-yl)amino]methyl}cyclobutyl) pyridin-2-ol [00387] 373.1 D 4-fluoro-3-[6-({[(6-hydroxy(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00388] 394.1 D 2-({[(6-(1H-indazol-5-yl)pyridazin- 3-yl)amino]methyl}cyclobutyl)pyr- idin-4-ol [00389] 373.1 D 4-fluoro-3-[6-({[(4-methoxy(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00390] 408.2 B (6-(1H-indazol-5-yl)pyridazin-3- yl){[(4-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00391] 387.2 A (6-(1H-indazol-6-yl)pyridazin-3- yl){[(4-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00392] 387.2 A 2-({[(6-(1H-indazol-6- yl)pyridazin-3- yl)amino]methyl}cyclobutyl)pyr- idin-4-ol [00393] 373.2 D 4-fluoro-3-[6-({[(4-hydroxy(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00394] 394.2 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-3- hydrobenzimidazol-2-one [00395] 391.0 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- pyrazol-4-ylpyridazin-3-yl)amine [00396] 325.0 C {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(1- methylpyrazol-4-yl)pyridazin-3- yl]amine [00397] 339.0 D 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-3,3-dimethylindolin-2-one [00398] 405.0 D 2-amino-7-(6-{[2-(4-fluorophenyl)- 2-methylpropyl]amino}pyridazin- 3-yl)-3-hydroquinazolin-4-one [00399] 405.1 C 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]benzenesulfonamide [00400] 414.4 A {4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}(methylsulfonyl)amine [00401] 428.3 B {3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}(methylsulfonyl)amine [00402] 428.3 B 3-{6-[(2-methyl-2-pyrimidin-2- ylpropyl)amino]pyridazin-3- yl}benzamide [00403] 349.0 D 4-fluoro-3-[6-({[(3-methoxy(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00404] 408.2 B (6-(1H-indazol-5-yl)pyridazin-3- yl){[(3-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00405] 387.2 B (6-(1H-indazol-6-yl)pyridazin-3- yl){[(3-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00406] 387.1 B 4-fluoro-3-[6-({[(5-methoxy(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00407] 408.1 D (6-(1H-indazol-5-yl)pyridazin-3- yl){[(5-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00408] 387.2 B (6-(1H-indazol-6-yl)pyridazin-3- yl){[(5-methoxy(2- pyridyl))cyclobutyl]methyl}amine [00409] 387.2 B 3-{[(6-(1H-indazol-6-yl)pyridazin- 3-yl)amino]methyl}-3-(2- pyridyl)cyclobutan-1-ol [00410] 373.1 D 3-{[(6-(1H-indazol-6-yl)pyridazin- 3-yl)amino]methyl}-3-(2- pyridyl)cyclobutan-1-ol [00411] 373.2 D 3-[6-({[(4- fluorophenyl)cyclobutyl]methyl}a- mino)pyridazin-3-yl]benzamide [00412] 377.3 A 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4- methylbenzamide [00413] 392.3 B 6-({[(6-(1H-indazol-5-yl)pyr- idazin-3- yl)amino]methyl}cyclobutyl)pyr- idine-3-carbonitrile [00414] 382.2 B 6-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-3,3- dimethylindolin-2-one [00415] 418.0 D 3-[6-({[(4-cyano-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00416] 385.1 B 2-[({[6-(3- carbamoylphenyl)pyridazin-3- yl]amino}methyl)cyclobutyl]pyr- idine-4-carboxamide [00417] 403.2 D 3-[6-({[(4-cyano(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4- fluorobenzamide [00418] 403.1 B 2-[({[6-(3-carbamoyl-6- fluorophenyl)pyridazin-3- yl]amino}methyl)cyclobutyl]pyr- idine-4-carboxamide [00419] 421.2 D 2-({[(6-(1H-indazol-5-yl)pyridazin- 3-yl)amino]methyl}cyclobutyl)pyr- idine-4-carbonitrile [00420] 382.1 A 2-({[(6-(1H-indazol-5-yl)pyridazin- 3-yl)amino]methyl}cyclobutyl)pyr- idine-4-carboxamide [00421] 400.2 C 3-[6-({[(6-cyano-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00422] 385.1 B 6-[({[6-(3- carbamoylphenyl)pyridazin-3- yl]amino}methyl)cyclobutyl]pyr- idine-2-carboxamide [00423] 403.2 D 6-({[(6-(1H-indazol-5-yl)pyr- idazin-3- yl)amino]methyl}cyclobutyl)pyr- idine-2-carbonitrile [00424] 382.1 B 6-({[(6-(1H-indazol-5-yl)pyr- idazin-3- yl)amino]methyl}cyclobutyl)pyr- idine-2-carboxamide [00425] 400.1 B (6-(1H-indazol-6-yl)pyridazin-3- yl){[(4-fluorophenyl)cyclo- butyl]methyl}amine [00426] 374.1 A (6-(1H-indazol-5-yl)pyridazin-3- yl){[(4-fluorophenyl)cyclo- butyl]methyl}amine [00427] 374.1 A 4-fluoro-3-[6-({[(1-methyl-6- oxo(2-hydropyridyl))cyclo- butyl]methyl}amino)pyridazin- 3-yl]benzamide [00428] 408.1 D 3-(6-{[(2- pyridylcyclobutyl)methyl]ami- no}pyridazin-3-yl)benzamide [00429] 360.2 A ({[(6-(1H-indazol-5-yl)pyridazin- 3-yl)amino]methyl}cyclobut- yl)methan-1-ol [00430] 310.2 D 1-({[6-(3-cyanophenyl)pyridazin- 3-yl]amino}methyl)cyclobutane- carboxylic acid [00431] 309.2 D 1-({[6-(3- carbamoylphenyl)pyridazin-3- yl]amino}methyl)cyclobutane- carboxylic acid [00432] 327.2 D 1-({[6-(3-cyanophenyl)pyridazin- 3-yl]amino}methyl)cyclobutane- carboxamide [00433] 308.2 D 3-(6-{[(carbamoylcyclo- butyl)methyl]amino}pyridazin-3- yl)benzamide [00434] 326.2 D methyl 3-(3-fluoro(2-pyridyl))-3- {[(6-(1H-indazol-5-yl)pyridazin-3- yl)amino]methyl}azetidine- carboxylate [00435] 434.2 D methyl 3-({[6-(3- carbamoylphenyl)pyridazin-3- yl]amino}methyl)-3-(3-fluoro(2- pyridyl))azetidinecarboxylate [00436] 437.2 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6-[3- (methylamino)(1H-indazol-5- yl)]pyridazin-3-yl}amine [00437] 404.1 A 2-fluoro-5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoic acid [00438] 397.0 B {2-fluoro-5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methylcarboxamide [00439] 410.0 B N-{5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1H-indazol-3- yl}acetamide [00440] 432.2 B 2-amino-N-{5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1H-indazol-3- yl)}acetamide [00441] 447.2 B {5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1H-indazol-3- yl)}(methylsulfonyl)amine [00442] 468.2 A 3-amino-5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1H- indazolecarboxamide [00443] 433.3 B [6-(3-aminophenyl)pyridazin-3- yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00444] 350.2 A [6-(4-aminophenyl)pyridazin-3- yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00445] 350.2 A (6-{3-[(2-aminoethyl)amino](1H- indazol-5-yl)}pyridazin-3-yl){[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00446] 433.0 A amino{3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamidine [00447] 392.2 B amino{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamidine [00448] 392.2 B 3-(6-{[(pyrazin-2- ylcyclobutyl)methyl]amino}pyr- idazin-3-yl)benzamide [00449] 361.3 D (6-(1H-indazol-6-yl)pyridazin-3- yl)[(pyrazin-2- ylcyclobutyl)methyl]amine [00450] 358.3 C (6-(1H-indazol-5-yl)pyridazin-3- yl)[(pyrazin-2- ylcyclobutyl)methyl]amine [00451] 358.3 C amino-N-{3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}amide [00452] 393.2 A 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzene-1,3- dicarboxylic acid [00453] 423.2 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzene-1,3- dicarboxamide [00454] 421.2 B 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]benzenecarboxamidine [00455] 377.2 D 3-[6-({[1-acetyl-3-(3-fluoro(2- pyridyl))azetidin-3- yl]methyl}amino)pyridazin-3- yl]benzamide [00456] 421.2 D 1-acetyl-3-(3-fluoro(2-pyridyl))-3- {[(6-(1H-indazol-5-yl)pyridazin-3- yl)amino]methyl}azetidine [00457] 418.2 D (6-(1H-indazol-5-yl)pyridazin-3- yl){[3-(3-fluoro(2- pyridyl))azetidin-3- yl]methyl}amine [00458] 376.2 D 3-[6-({[3-(3-fluoro-2- pyridyl)azetidin-3- yl]methyl}amino)pyridazin-3- yl]benzamide [00459] 379.2 D 3-(3-fluoro(2-pyridyl))-3-{[(6- (1H-indazol-5-yl)pyridazin-3- yl)amino]methyl}-1- (methylsulfonyl)azetidine [00460] 454.2 D 3-[6-({[3-(3-fluoro(2-pyridyl))-1- (methylsulfonyl)azetidin-3- yl]methyl}amino)pyridazin-3- yl]benzamide [00461] 457.2 D (6-(1H-indazol-5-yl)pyridazin-3- yl){[3-(3-fluoro(2- pyridyl))azetidin-3- yl]methyl}(methylsulfonyl)amine [00462] 454.2 D amino{5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1H-indazol-3- yl)}carboxamidine [00463] 432.2 B 3-[6-({[3-(4-fluorophenyl)oxetan- 3-yl]methyl}amino)pyridazin-3- yl]benzamide [00464] 379.0 D [2-(4-fluorophenyl)-2- methylpropyl](6-{3- [(methylethyl)amino](1H-indazol- 5-yl)}pyridazin-3-yl)amine [00465] 419.3 A [6-(2-aminopyrimidin-5- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00466] 339.2 B [2-(4-fluorophenyl)-2- methylpropyl]{6-[3- (methylamino)(1H-indazol-5- yl)]pyridazin-3-yl}amine [00467] 391.3 B [2-(4-fluorophenyl)-2- methylpropyl][6-(2- methoxypyrimidin-5- yl)pyridazin-3-yl]amine [00468] 354.2 C [2-(4-fluorophenyl)-2- methylpropyl][6-(2-methoxy(3- pyridyl))pyridazin-3-yl]amine [00469] 353.1 A {6-[3-(ethylamino)(1H-indazol-5- yl)]pyridazin-3-yl}[2-(4- fluorophenyl)-2- methylpropyl]amine [00470] 405.2 A [2-(4-fluorophenyl)-2- methylpropyl](6-phenylpyridazin- 3-yl)amine [00471] 322.2 A 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)hydropyridin-2-one [00472] 339.2 B [6-(2-amino(4-pyridyl))pyridazin- 3-yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00473] 338.2 B [6-(4-aminophenyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00474] 337.1 A [6-(3-aminophenyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00475] 337.1 A 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridin-2-ol [00476] 339.1 B 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-3-hydropyrimidin-2-one [00477] 340.1 D 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1,3,4-oxadiazolin-2-one [00478] 330.0 C [6-(6-amino(3-pyridyl))pyridazin- 3-yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00479] 338.2 A [2-(4-fluorophenyl)-2- methylpropyl](6-vinylpyridazin- 3-yl)amine [00480] 272.0 B [6-(5-aminopyrazol-3- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00481] 327.2 B [2-(4-fluorophenyl)-2- methylpropyl][6-(6-methoxy(2- pyridyl))pyridazin-3-yl]amine [00482] 353.1 A N-[4-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)imidazol-2-yl]acetamide [00483] 369.2 C 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-2-carbonitrile [00484] 348.0 C [6-(2-aminoimidazol-4- yl)pyridazin-3-yl][2-(4- fluorophenyl)-2- methylpropyl]amine [00485] 327.2 B 5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)pyridine-2-carboxamide [00486] 366.1 B 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)pyridin-2-ol [00487] 339.1 B {6-[6-(aminomethyl)(3- pyridyl)]pyridazin-3-yl}[2-(4- fluorophenyl)-2- methylpropyl]amine [00488] 352.2 B [2-(4-fluorophenyl)-2- methylpropyl][6-(2- fluorophenyl)pyridazin-3- yl]amine [00489] 340.1 A [2-(4-fluorophenyl)-2- methylpropyl][6-(3- fluorophenyl)pyridazin-3- yl]amine [00490] 340.1 A [2-(4-fluorophenyl)-2- methylpropyl][6-(4- fluorophenyl)pyridazin-3- yl]amine [00491] 340.1 B [6-(2-chlorophenyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00492] 356.1 A [6-(3-chlorophenyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00493] 356.1 A [6-(4-chlorophenyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00494] 356.1 B 4-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)benzenecarbonitrile [00495] 347.1 B [2-(4-fluorophenyl)-2- methylpropyl](6-(3- pyridyl)pyridazin-3-yl)amine [00496] 323.1 B [6-(6-amino(2-pyridyl))pyridazin- 3-yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00497] 338.2 B N-{[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-2-pyridyl]methyl}acetamide [00498] 394.2 C N-{[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)(2- pyridyl)]methyl}methoxycarbox- amide [00499] 410.2 C {6-[3-(ethylamino)(1H-indazol-5- yl)]pyridazin-3-yl}{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00500] 418.2 A 3-(6-{[2-methyl-2- (phenylmethoxy)propyl]ami- no}pyridazin-3-yl)benzamide [00501] 377.0 D 3-(6-{[2-methyl-2- (phenylmethoxy)propyl]ami- no}pyridazin-3- yl)benzenecarbonitrile [00502] 359.0 D [2-(4-fluorophenyl)-2- methylpropyl](6-(2- pyridyl)pyridazin-3-yl)amine [00503] 323.1 B N-{4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]imidazol-2- yl}acetamide [00504] 382.1 D [6-(2-aminoimidazol-4- yl)pyridazin-3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00505] 340.1 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- {3-[(methylethyl)amino](1H- indazol-5-yl)}pyridazin-3- yl)amine [00506] 432.2 A {6-[3-(ethylamino)(1H-indazol-5- yl)]pyridazin-3-yl}[(2- pyridylcyclobutyl)methyl]amine [00507] 400.2 A [6-((1E)prop-1-enyl)pyridazin-3- yl][2-(4-fluorophenyl)-2- methylpropyl]amine [00508] 286.0 B [2-(4-fluorophenyl)-2- methylpropyl][6-(2-methylprop- 1-enyl)pyridazin-3-yl]amine [00509] 300.0 B [2-(4-fluorophenyl)-2- methylpropyl][6-(2- methylpropyl)pyridazin-3- yl]amine [00510] 302.0 B ethyl 3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)propanoate [00511] 346.0 D 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)pyridine-3-carboxamide [00512] 366.1 B (6-ethylpyridazin-3-yl)[2-(4- fluorophenyl)-2- methylpropyl]amine [00513] 274.0 C [3-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl]methan-1-ol [00514] 352.2 B (tert-butoxy)-N-{[3-(6-{[2-(4- fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)phenyl]methyl}carboxamide [00515] 451.1 B {6-[3- (aminomethyl)phenyl]pyridazin- 3-yl}[2-(4-fluorophenyl)-2- methylpropyl]amine [00516] 351.2 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6-[2- (trifluoromethoxy)phenyl]pyr- idazin-3-yl}amine [00517] 419.1 A {2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}methan- 1-ol [00518] 365.2 B [2-(4-fluorophenyl)-2- methylpropyl][6-(5-methoxy(2- pyridyl))pyridazin-3-yl]amine [00519] 353.2 B 6-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)pyridin-3-ol [00520] 339.1 A [6-(5-amino(2-pyridyl))pyridazin- 3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00521] 351.2 A [2-(4-fluorophenyl)-2- methylpropyl](6-{3-[(2,2,2- trifluoroethyl)amino](1H-indazol- 5-yl)}pyridazin-3-yl)amine [00522] 459.2 A [6-(6-amino(3-pyridyl))pyridazin- 3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00523] 351.2 A [6-(4-amino-3- fluorophenyl)pyridazin-3- yl]{[(3-fluoro(2- pyridyl))cyclobutyl]meth- yl}amine [00524] 368.1 A (6-benzotriazol-6-ylpyridazin-3- yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00525] 376.1 A 4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]indolin-2-one [00526] 390.1 B (6-benzimidazol-5-ylpyridazin-3- yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00527] 375.1 A N-{3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}aceta- mide [00528] 392.2 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(4- morpholin-4-ylphenyl)pyridazin- 3-yl]amine [00529] 420.2 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(2- methylpyrimidin-5-yl)pyridazin- 3-yl]amine [00530] 351.2 D [5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin- 3-yl)(1H-indazol-3- yl)]dimethylamine [00531] 405.2 B [2-(4-fluorophenyl)-2- methylpropyl][6-(3-{[2- (phenylmethoxy)ethyl]amino}(1H- indazol-5-yl))pyridazin-3-yl]amine [00532] 511.2 A 2-{[5-(6-{[2-(4-fluorophenyl)-2- methylpropyl]amino}pyridazin-3- yl)-1H-indazol-3-yl]amino}ethan- 1-ol [00533] 421.2 A {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- pyrimidin-2-ylpyridazin-3- yl)amine [00534] 337.0 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- pyrazin-2-ylpyridazin-3-yl)amine [00535] 337.0 B ethyl 6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazine-3-carboxylate [00536] 331.0 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]propan-2-ol [00537] 317.0 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- phenylpyridazin-3-yl)amine [00538] 335.1 A {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- vinylpyridazin-3-yl)amine [00539] 285.1 D (6-ethylpyridazin-3-yl){[(3- fluoro(2-pyridyl))cyclobutyl]meth- yl}amine [00540] 287.1 D N-{4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}acet- amide [00541] 392.2 A [6-(2-aminopyrimidin-5- yl)pyridazin-3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00542] 352.1 B N-{5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}acetamide [00543] 394.2 C N-{5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}methoxycarboxamide [00544] 410.1 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(5- methoxy(2-pyridyl))pyridazin-3- yl]amine [00545] 366.2 B 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyridin-3-ol [00546] 352.1 A {5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}(methylsulfonyl)amine [00547] 430.0 D [6-(2,3-difluorophenyl)pyridazin- 3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00548] 371.0 A {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6- (3-fluoro(2-pyridyl))pyridazin-3- yl]amine [00549] 354.0 B 3-{6-[(1-methyl-1- phenylethyl)amino]pyridazin-3- yl}benzamide [00550] 333.2 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]indolin-2-one [00551] 390.1 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1H-2- hydroindazol-3-one [00552] 391.1 A N-{3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}(methylamino)carbox- amide [00553] 407.2 A N-{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}(methylamino)car- boxamide [00554] 407.2 A tert-butyl 4-{5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}piperazinecarboxylate [00555] 521.3 D 2-({5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}amino)acetamide [00556] 409.1 C {6-[2-(aminomethyl)-5- fluorophenyl]pyridazin-3-yl} {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00557] 382.2 C {6-[2- (aminomethyl)phenyl]pyridazin-3- yl}{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00558] 364.2 D {6-[4- (aminomethyl)phenyl]pyridazin- 3-yl}{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00559] 364.2 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6- (2-piperazinylpyrimidin-5- yl)pyridazin-3-yl]amine [00560] 421.2 D (6-(1H-indazol-6-yl)pyridazin-3- yl)(2,2-difluoro-2-(2- pyridyl)ethyl)amine [00561] 353.1 D 3-{6-[(2,2-difluoro-2-(2- pyridyl)ethyl)amino]pyridazin-3- yl}benzamide [00562] 356.1 D [6-(3-chloro(2-pyridyl))pyridazin- 3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00563] 370.1 C 6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazine-3-carbonitrile [00564] 284.0 D 1-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]ethan-1-one [00565] 301.1 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6- (2-methyl(3-pyridyl))pyridazin- 3-yl]amine [00566] 350.2 C 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyridine-2- carbonitrile [00567] 361.1 C 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyridine-2- carboxamide [00568] 379.2 C methyl 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyridine-2- carboxylate [00569] 394.2 C 2-{3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- pyridyl}propan-2-ol [00570] 394.2 D amino-N-{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}amide [00571] 393.0 A 2-amino-2-{3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}acetamide [00572] 407.0 C {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- pyridazin-4-ylpyridazin-3- yl)amine [00573] 337.2 D 3-[6-({[3,3-difluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00574] 414.0 B (6-(1H-indazol-5-yl)pyridazin-3- yl){[3,3-difluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00575] 411.0 B 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-(methylethyl)- 1H-2-hydroindazol-3-one [00576] 433.1 B 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1-(methylethyl)- 1H-2-hydroindazol-3-one [00577] 433.1 C 3-{6-[(1-methyl-1- phenylethyl)amino]pyridazin-3- yl}benzenecarbonitrile [00578] 315.0 B 3-{6-[(tert-butyl)amino]pyridazin- 3-yl}benzamide [00579] 271.1 C 3-[6- (phenylcarbonylamino)pyridazin- 3-yl]benzamide [00580] 319.1 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6-(2- pyridyl)pyridazin-3-yl)amine [00581] 336.1 B 3-{6-[(1-methyl-1-(2- pyridyl)ethyl)amino]pyridazin-3- yl}benzamide [00582] 334.1 D {3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- pyridyl}methan-1-ol [00583] 366.2 C 3-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00584] 363.1 A (6-(1H-indazol-5-yl)pyridazin-3- yl)[(4- fluorophenyl)cyclobutyl]amine [00585] 360.1 A 4-{6-[(1-methyl-1- phenylethyl)amino]pyridazin-3- yl}benzamide [00586] 333.1 C (6-(1H-indazol-5-yl)pyridazin-3- yl)(1-methyl-1-phenylethyl)amine [00587] 330.2 B [6-(6-amino(3-pyridyl))pyridazin- 3-yl](1-methyl-1-phenylethyl)a- mine [00588] 306.2 B amino-N-{5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](2- pyridyl)}amide [00589] 394.2 B (1-methyl-1-phenylethyl)(6- phenylpyridazin-3-yl)amine [00590] 290.1 B 1-amino-1-{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-2- methylpropan-2-ol [00591] 422.2 D amino-N-{5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}amide [00592] 395.2 D (6-(1H-indazol-6-yl)pyridazin-3- yl){[3,3-difluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00593] 411.1 B [6-(2-amino(3-pyridyl))pyridazin- 3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00594] 351.1 B [6-(6-amino-5-fluoro(3- pyridyl))pyridazin-3-yl]{[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00595] 369.1 A 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]indolin-2-one [00596] 390.1 B [6-(2-aminopyrimidin-5- yl)pyridazin-3-yl][(4- fluorophenyl)cyclobutyl]amine [00597] 337.0 B amino-N-[4-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)phenyl]amide [00598] 378.2 A amino-N-{4-[6-({[3,3-difluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}amide [00599] 429.0 A 3-(6-{[1-(4-fluorophenyl)- isopropyl]amino}pyridazin- 3-yl)benzamide [00600] 351.1 B 3-(6-{[(2- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00601] 363.2 A 3-(6-{[1-(3-fluorophenyl)- isopropyl]amino}pyridazin-3- yl)benzamide [00602] 351.1 B 3-(6-{[(3- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00603] 363.2 B 3-{6-[(2-hydroxy-tert- butyl)amino]pyridazin-3- yl}benzamide [00604] 287.1 D 3-{6-[(2- pyridylcyclobutyl)amino]pyridazin- 3-yl}benzamide [00605] 346.1 D (phenylcyclobutyl)(6- phenylpyridazin-3-yl)amine [00606] 302.2 B 3-{6- [(phenylcyclobutyl)amino]pyr- idazin-3-yl}benzamide [00607] 345.1 B 3-(6-{[(3-fluoro-2- pyridyl)cyclobutyl]amino}pyri- dazin-3-yl)benzamide [00608] 364.1 B 3-(6-{[(5-fluoro-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00609] 364.1 B 4-fluoro-3-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00610] 381.1 A [(4-fluorophenyl)cyclobutyl][6- (6-methoxy(2-pyridyl))pyridazin- 3-yl]amine [00611] 351.1 B (6-benzimidazol-5-ylpyridazin-3- yl)[(4- fluorophenyl)cyclobutyl]amine [00612] 360.1 A [(4-fluorophenyl)cyclobutyl](6- pyrazol-4-ylpyridazin-3-yl)amine [00613] 310.1 B 3-{6-[(1,3-thiazol-2- ylcyclobutyl)amino]pyridazin-3- yl}benzamide [00614] 352.2 D 4-fluoro-3-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00615] 382.1 B 4-fluoro-3-(6-{[1-(4-fluorophenyl)- isopropyl]amino}pyridazin-3- yl)benzamide [00616] 369.1 A 3-(6-{[(4-methoxy-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00617] 376.0 D [6-(3-fluoro(4-pyridyl))pyridazin- 3-yl][(4- fluorophenyl)cyclobutyl]amine [00618] 339.2 B [(4-fluorophenyl)cyclobutyl](6-(4- pyridyl)pyridazin-3-yl)amine [00619] 321.2 B 4-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)pyridine-2- carbonitrile [00620] 346.2 B 4-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)pyridine- 2-carboxamide [00621] 364.2 B [4-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3- yl)phenyl](methylsulfonyl)amine [00622] 413.1 B [(4-fluorophenyl)cyclobutyl][6-(2- methoxy(3-pyridyl))pyridazin-3- yl]amine [00623] 351.2 A [(4-fluorophenyl)cyclobutyl]{6-[2- (2,2,2-trifluoroethoxy)(3- pyridyl)]pyridazin-3-yl}amine [00624] 419.2 B 3-(6-{[(4- chlorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00625] 379.1 B 3-(6-{[(4- cyanophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00626] 370.1 D 3-(6-{[(3-chloro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)-4-fluorobenzamide [00627] 398.1 A [3-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3- yl)phenyl](methylsulfonyl)amine [00628] 413.0 A 3-(6-{[(4- carbamoylphenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzamide [00629] 388.2 D [(4-fluorophenyl)cyclobutyl][6-(2- methyl(4-pyridyl))pyridazin-3- yl]amine [00630] 335.2 B [(4-fluorophenyl)cyclobutyl][6-(2- methoxy(4-pyridyl))pyridazin-3- yl]amine [00631] 351.2 B 3-(6-{[(6-methoxy-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00632] 376.1 B 4-fluoro-3-(6-{[(6-methoxy(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00633] 394.1 A [3-(6-{[(6-methoxy(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl](methylsulfon- yl)amine [00634] 426.1 B [3-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl](methylsulfon- yl)amine [00635] 414.1 B amino-N-[4-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl]amide [00636] 379.2 B (6-(1H-indazol-6-yl)pyridazin-3- yl)[(3-fluoro(2- pyridyl))cyclobutyl]amine [00637] 361.1 B (6-benzimidazol-6-ylpyridazin-3- yl)[(3-fluoro(2- pyridyl))cyclobutyl]amine [00638] 361.2 B 3-[6-({[6-(difluoromethoxy)-2- pyridyl]cyclobutyl}amino)pyr- idazin-3-yl]benzamide [00639] 412.0 A 3-[6-({[6-(difluoromethoxy)(2- pyridyl)]cyclobutyl}amino)pyr- idazin-3-yl]-4-fluorobenzamide [00640] 430.1 A {3-[6-({[6-(difluoromethoxy)(2- pyridyl)]cyclobutyl}amino)pyr- idazin-3-yl]phenyl}(methyl- sulfonyl)amine [00641] 462.1 A 4-fluoro-3-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)benzoic acid [00642] 382.2 B [4-fluoro-3-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)phenyl]-N-(2- hydroxy-2- methylpropyl)carboxamide [00643] 453.2 B 3-(6-{[(3-bromo(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)-4-fluorobenzamide [00644] 442.1 A 3-(6-{[1-(3-chloro(2-pyridyl))- isopropyl]amino}pyridazin-3-yl)- 4-fluorobenzamide [00645] 386.1 B 4-chloro-3-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00646] 398.1 B [4-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)(2-pyridyl)]-N- methylcarboxamide [00647] 378.2 B (6-(1H-indazol-5-yl)pyridazin-3- yl)[(3-fluoro(2- pyridyl))cyclobutyl]amine [00648] 361.1 B [6-(6-fluoro(1H-indazol-5- yl))pyridazin-3-yl][(3-fluoro(2- pyridyl))cyclobutyl]amine [00649] 379.1 B amino-N-[4-fluoro-3-(6-{[(3- fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl]amide [00650] 398.1 B amino[4-fluoro-3-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl]sulfonamide [00651] 433.1 B amino[3-fluoro-4-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl]sulfonamide [00652] 433.1 B amino-N-[3-fluoro-4-(6-{[(3- fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)phenyl]amide [00653] 397.1 B 4-fluoro-3-(6-{[1-methyl-1-(6- oxo(2- hydropyridyl))ethyl]amino}pyr- idazin-3-yl)benzamide [00654] 368.2 D 3-[6-({1-[6-(difluoromethoxy)(2- pyridyl)]- isopropyl}amino)pyridazin-3-yl]- 4-fluorobenzamide [00655] 418.1 A 3-[6-({1-[6-(difluoromethoxy)(2- pyridyl)]- isopropyl}amino)pyridazin-3- yl]benzamide [00656] 400.2 B {3-[6-({1-[6-(difluoromethoxy)(2- pyridyl)]- isopropyl}amino)pyridazin-3- yl]phenyl}(methylsulfonyl)amine [00657] 450.1 A 3-(6-{[(4-cyano(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)-4-fluorobenzamide [00658] 389.1 D 2-({[6-(3-carbamoyl-6- fluorophenyl)pyridazin-3- yl]amino}cyclobutyl)pyridine-4- carboxamide [00659] 407.1 D 3-(6-{[(5-cyano(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)-4-fluorobenzamide [00660] 389.2 D 3-(6-{[(6-cyano(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)-4-fluorobenzamide [00661] 389.2 B 6-({[6-(3-carbamoyl-6- fluorophenyl)pyridazin-3- yl]amino}cyclobutyl)pyridine-2- carboxamide [00662] 407.2 D 4-fluoro-3-(6-{[(3-hydroxy(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00663] 380.2 D 4-fluoro-3-(6-{[(3-methoxy(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00664] 394.2 C 3-[6-({[3-(difluoromethoxy)(2- pyridyl)]cyclobutyl}amino)pyr- idazin-3-yl]-4-fluorobenzamide [00665] 430.2 C 3-[6-({[3-(difluoromethoxy)-2- pyridyl]cyclobutyl}amino)pyr- idazin-3-yl]benzamide [00666] 412.2 D {3-[6-({[3-(difluoromethoxy)(2- pyridyl)]cyclobutyl}amino)pyr- idazin-3-yl]phenyl}(methylsulfon- yl)amine [00667] 462.2 C 4-fluoro-3-(6-{[(5-methoxy(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00668] 394.2 D 3-[6-({[5-(difluoromethoxy)(2- pyridyl)]cyclobutyl}amino)pyr- idazin-3-yl]-4-fluorobenzamide [00669] 430.1 D 4-fluoro-3-(6-{[(5-hydroxy(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzamide [00670] 380.1 D [(3-fluoro(2- pyridyl))cyclobutyl](6- vinylpyridazin-3-yl)amine [00671] 271.1 D 4-fluoro-3-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)benzenecarbonitrile [00672] 364.1 B [(3-fluoro(2- pyridyl))cyclobutyl](6- phenylpyridazin-3-yl)amine [00673] 321.1 B (6-cyclohexylpyridazin-3-yl)[(3- fluoro(2- pyridyl))cyclobutyl]amine [00674] 327.2 C (6-cyclohex-1-enylpyridazin-3- yl)[(3-fluoro(2- pyridyl))cyclobutyl]amine [00675] 325.2 C (6-cyclohex-1-enylpyridazin-3- yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00676] 339.2 A 4-fluoro-3-{6- [(methylcyclobutyl)amino]pyr- idazin-3-yl}benzamide [00677] 301.1 D (6-cyclohexylpyridazin-3-yl){[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00678] 341.2 B ethyl (2E)-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]prop-2-enoate [00679] 357.2 D ethyl (2E)-3-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)prop-2-enoate [00680] 343.1 D diethyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]propane-1,3- dioate [00681] 417.2 D (1S,2S)-2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]cyclopropanecarboxamide [00682] 342.2 D (2S,1R)-2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]cyclopropanecarboxamide [00683] 342.2 D amino-N-{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]cyclohex- yl}amide [00684] 399.3 B amino-N-{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]cyclohex- yl}amide [00685] 399.2 C 4-fluoro-3-(6-{[(3-fluoro(2- pyridyl))cyclopentyl]amino}pyr- idazin-3-yl)benzamide [00686] 396.2 A amino-N-{3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]cyclobutyl}a- mide [00687] 371.2 C amino-N-{3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]cyclobut- yl}amide [00688] 371.2 B amino-N-{4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]cyclohex-3- enyl}amide [00689] 397.2 B phenylmethyl 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]azetidine- carboxylate [00690] 448.2 D (6-azetidin-3-ylpyridazin-3- yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00691] 314.2 D methyl 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]azetidine- carboxylate [00692] 372.2 D 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]azetidine- carboxamide [00693] 357.2 D 1-acetyl-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]azetidine [00694] 356.2 D ethyl 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoxazole-3- carboxylate [00695] 398.2 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoxazole-3- carboxylic acid [00696] 370.2 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoxazole-3- carboxamide [00697] 369.2 B amino-N-{5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1H-indazol-3- yl)}amide [00698] 433.3 A 4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1- methylimidazole-2-carboxamide [00699] 382.3 D 4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzamide [00700] 408.2 B 4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [00701] 394.1 B 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzamide [00702] 408.2 B 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [00703] 394.1 A 4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzoic acid [00704] 409.2 D 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzoic acid [00705] 409.2 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-oxazole- 2-carboxamide [00706] 369.2 B 4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]imidazole-2- carboxamide [00707] 368.2 C 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoxazole-5- carboxamide [00708] 369.2 A 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrazole-5- carboxamide [00709] 368.3 B 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1- methylpyrazole-5-carboxamide [00710] 382.3 B 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1- methylpyrazole-3-carboxamide [00711] 382.3 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-oxazole-5- carboxamide [00712] 369.1 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-4- carboxamide [00713] 385.1 D 1-[(6-{[(3-fluoro-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)methyl]pyrazole-4- carboxamide [00714] 368.1 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,2,4- oxadiazole-3-carboxamide [00715] 370.2 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-imidazoline- 5-carboxamide [00716] 370.3 D methyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- imidazoline-5-carboxylate [00717] 385.3 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-imidazoline- 5-carboxylic acid [00718] 371.3 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-oxazole-4- carboxamide [00719] 369.2 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-5- carboxamide [00720] 385.2 A methyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-oxazole-4- carboxylate [00721] 384.2 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyridazin-3- yl}amine [00722] 515.4 D methyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole- 4-carboxylate [00723] 400.2 D methyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-oxazole- 5-carboxylate [00724] 384.2 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]imidazole-4- carboxamide [00725] 368.2 B methyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]imidazole-4- carboxylate [00726] 383.3 D 4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-2- carboxamide [00727] 385.2 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-2- carboxamide [00728] 385.2 B 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,2,4- oxadiazole-5-carboxamide [00729] 370.1 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4H-1,2,4- triazole-3-carboxamide [00730] 369.2 C methyl 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1- methylimidazole-4-carboxylate [00731] 397.3 D 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1- methylimidazole-4-carboxamide [00732] 382.3 D 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1- methylimidazole-5-carboxamide [00733] 382.3 B 2-(6-{[(3-fluoro-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)-1,3-thiazole-5- carboxamide [00734] 371.2 B 5-(6-{[(3-fluoro(2- pyridyl))cyclobutyl]amino}pyr- idazin-3-yl)-2-hydroxybenzamide [00735] 380.1 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]thiophene-2- carboxamide [00736] 384.1 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl][(3-fluoro(2- pyridyl))cyclobutyl]amine [00737] 376.2 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3,4- thiadiazole-2-carboxamide [00738] 386.1 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- (1,3-thiazol-2-yl)pyridazin-3- yl)amine [00739] 342.1 B (6-(2H-1,2,3,4-tetraazol-5- yl)pyridazin-3-yl){[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00740] 327.2 D 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3,4- oxadiazole-2-carboxamide [00741] 370.2 C 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-methyl-1,3- thiazole-5-carboxamide [00742] 399.2 B 2-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)-1,3-thiazole- 5-carboxamide [00743] 370.2 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-5- carboxylic acid [00744] 386.2 C 5-(6-{[(3-fluoro-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)thiophene-2- carboxamide [00745] 370.1 B 5-(6-{[(4- fluorophenyl)cyclobutyl]ami- no}pyridazin-3-yl)thiophene-2- carboxamide [00746] 369.1 B 5-(6-{[(3-fluoro-2- pyridyl)cyclobutyl]amino}pyr- idazin-3-yl)thiophene-2- carboxylic acid [00747] 371.1 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-5- carbonitrile [00748] 367.1 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]thiophene-2- carboxylic acid [00749] 385.0 B 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-hydroxy-1,3- thiazole-5-carboxamide [00750] 401.1 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-3- pyrazolino[3,4-d]1,3-thiazol-3-one [00751] 398.3 D 2-[6-({1-[6-(difluoromethoxy)(2- pyridyl)]- isopropyl}amino)pyridazin-3-yl]- 1,3-thiazole-5-carboxamide [00752] 407.1 B {2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methan-1-ol [00753] 372.2 B [6-(5-(2H-1,2,3,4-tetraazol-5- yl)(1,3-thiazol-2-yl))pyridazin-3- yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00754] 410.2 B 5-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol- 5-yl}-1,3,4-oxadiazolin-2-one [00755] 426.2 B ethyl 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- hydroxypyrazole-4-carboxylate [00756] 413.1 D 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-3-pyrazolin- 5-one [00757] 341.1 B 3-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol- 5-yl}-1,2,4-triazolin-5-one [00758] 425.2 A 3-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol- 5-yl}-1,2,4-oxadiazolin-5-one [00759] 426.2 B ethyl 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-hydroxy-1,3- thiazole-5-carboxylate [00760] 430.1 D 2-(6-{[2-(3-fluoro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)-1,3-thiazole-5-carboxamide [00761] 373.2 A 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-methoxy-1,3- thiazole-5-carboxamide [00762] 415.1 A 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-methoxy-1,3- thiazole-5-carboxylic acid [00763] 416.2 C 1-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol- 5-yl}ethan-1-ol [00764] 386.2 B 2,2,2-trifluoro-1-{2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}ethan-1-ol [00765] 440.2 B {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-(methylethyl)carboxamide [00766] 427.3 B ethyl 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-4- carboxylate [00767] 514.0 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-3- pyrrolino[3,4-d]1,3-thiazol-6-one [00768] 396.1 B 1-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}ethan-1-one [00769] 384.2 C 2-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}propan-2-ol [00770] 400.3 C 1,1,1-trifluoro-2-{2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}propan-2-ol [00771] 454.2 C {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-methylcarboxamide [00772] 399.3 A 3-(6-{[(2- pyridylcyclobutyl)methyl]ami- no}pyridazin-3- yl)benzenecarbonitrile [00773] 342.1 B 3-(6-{methyl[(2- pyridylcyclobutyl)methyl]ami- no}pyridazin-3-yl)benzamide [00774] 374.2 D 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrazine-2- carbonitrile [00775] 362.1 B 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrazine-2- carboxamide [00776] 380.2 C 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-hydroxy-1,3- thiazole-5-carbonitrile [00777] 383.1 D 2-(6-{[(2- pyridylcyclobutyl)methyl]ami- no}pyridazin-3-yl)-1,3-thiazole- 5-carboxamide [00778] 367.1 A 2-(6-{[(2- pyridylcyclobutyl)methyl]ami- no}pyridazin-3-yl)-1,3-thiazole-5- carboxylic acid [00779] 368.1 C 3-{5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-thienyl}- 1,2,4-triazolin-5-one [00780] 424.1 A 3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,2,4- triazolin-5-one [00781] 342.2 C amino{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methane-1-thione [00782] 401.2 A 2,2,2-trifluoro-1-{2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}ethane-1,1-diol [00783] 456.2 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6-[5- (2,2,2-trifluoroethyl)(1,3-thiazol- 2-yl)]pyridazin-3-yl}amine [00784] 424.2 B 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]thiophene-2- carbonitrile [00785] 366.2 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]thiopheno[2,3-c]3-pyrrolin- 6-one [00786] 396.2 B {6-[5-(1-amino-2,2,2- trifluoroethyl)(1,3-thiazol-2- yl)]pyridazin-3-yl}{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00787] 439.2 B [6-(2-aminopyrimidin-4- yl)pyridazin-3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00788] 352.3 B 2-{5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,2,3,4- tetraazol-2-yl}acetamide [00789] 384.3 D {6-[2-(2-aminoethyl)(1,2,3,4- tetraazol-5-yl)]pyridazin-3-yl}{[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00790] 370.3 D [6-(3-(2H-1,2,3,4-tetraazol-5- yl)phenyl)pyridazin-3-yl]{[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00791] 403.1 A phenylmethyl 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]carbonylamino}acetate [00792] 450.1 D 3-{3-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-1,2,4- triazolin-5-one [00793] 418.3 B 3-{4-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-1,2,4- triazolin-5-one [00794] 436.3 A {6-[5-(aminomethyl)(1,3-thiazol- 2-yl)]pyridazin-3-yl}{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00795] 371.3 B N-((2-(6-((1-(3-fluoropyridin-2- yl)cyclobutyl)methylamino)pyr- idazin-3-yl)thiazol-5-yl)methyl)- 2-methylpropane-2-sulfinamide [00796] 475.3 B {6-[5-(aminoethyl)(1,3-thiazol-2- yl)]pyridazin-3-yl}{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00797] 385.3 B {6-[5-(3-aminooxetan-3-yl)(1,3- thiazol-2-yl)]pyridazin-3-yl}{[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00798] 413.2 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidine-4- carboxamide [00799] 380.3 A {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-(2- hydroxyethyl)carboxamide [00800] 429.2 A ethyl 5-chloro-2-[5-chloro-6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole-4- carboxylate [00801] 482.2 D N-{4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}acetamide [00802] 394.3 C {4-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidin-2- yl}(methylsulfonyl)amine [00803] 430.3 D (2E)-3-amino-3-{2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-2-azaprop-2-enenitrile [00804] 409.1 B N-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)acetamide [00805] 413.3 A ({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)(methylsulfonyl)amine [00806] 449.2 B N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)methoxycarboxamide [00807] 429.2 B 2,2-difluoro-1-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}ethan-1-ol [00808] 422.2 B N-(carbamoylmethyl)[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [00809] 359.1 441.3 D 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5-yl) morpholin-4-yl ketone [00810] 455.3 C N-(2-aminoethyl){2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00811] 428.4 A N-(2,3-dihydroxypropyl){2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00812] 459.3 A {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-pyrrolidin-3-ylcarboxamide [00813] 454.3 A 2-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol- 5-yl}acetamide [00814] 399.3 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(5- pyrazol-4-yl(1,3-thiazol-2- yl))pyridazin-3-yl]amine [00815] 408.3 A {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6- (5-pyrazol-3-yl(1,3-thiazol-2- yl))pyridazin-3-yl]amine [00816] 408.3 A 4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidine-2- carboxamide [00817] 380.3 D 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]pyrimidine-4- carboxamide [00818] 380.3 B [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-pyrazol-5- ylcarboxamide [00819] 368.1 B N-(carbamoylmethyl){2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00820] 442.3 A 4-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}carbonyl)piperazine-2- carboxamide [00821] 497.3 B [6-(5-chloro(1,3-thiazolino[5,4- b]pyridin-2-yl))pyridazin-3- yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00822] 427.1 C {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- (1,3-thiazolino[5,4-b]pyridin-2- yl)pyridazin-3-yl)amine [00823] 393.1 B [6-(5-amino(1,3- thiazolino[5,4-b]pyridin-2- yl))pyridazin-3-yl]{[(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00824] 408.1 B amino{4-fluoro-3-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}sulfonamide [00825] 447.2 A 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl) 3-hydroxypyrrolidinyl ketone [00826] 455.3 C 4-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}carbonyl)-1,4- thiazaperhydroine-1,1-dione [00827] 503.3 B N-(1,1-dioxothiolan-3-yl){2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00828] 503.3 A {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-[2- (methylsulfonyl)ethyl]carboxamide [00829] 491.2 A 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl) 3-hydroxypiperidyl ketone [00830] 469.3 C {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- pyrazolo[5,4-d]1,3-thiazol-5- ylpyridazin-3-yl)amine [00831] 382.1 A 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl) 4-hydroxypiperidyl ketone [00832] 469.3 C 4-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}carbonyl)piperazin-2-one [00833] 468.3 C {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-(oxolan-2- ylmethyl)carboxamide [00834] 469.3 B 1-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}carbonyl)piperidine-3- carboxamide [00835] 496.3 C [6-(3-(2H-1,2,3,4-tetraazol-5- yl)phenyl)pyridazin-3-yl][2-(3- fluoro(2-pyridyl))-2- methylpropyl]amine [00836] 391.3 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3- thiazolino[5,4-b]pyridine-5- carboxamide [00837] 436.1 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(5- methoxy(1,3-thiazolino[5,4- b]pyridin-2-yl))pyridazin-3- yl]amine [00838] 423.1 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3- thiazolino[5,4-b]pyridin-5-ol [00839] 409.1 B N-((2R)-2,3-dihydroxypropyl){2- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00840] 459.3 B N-((2S)-2,3-dihydroxypropyl){2- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00841] 459.3 A N-(2-amino-3,3,3- trifluoropropyl){2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00842] 496.3 B N-(3-amino-2,2-difluoropropyl){2- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00843] 478.3 A {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N,N-dimethylcarboxamide [00844] 414.3 C N-(2,2-difluoro-3- hydroxypropyl){2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00845] 479.3 A {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-(2-oxopyrrolidin-3- yl)carboxamide [00846] 468.3 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00847] 396.3 A 4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00848] 414.3 A 2-amino-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)acetamide [00849] 428.1 A ((2S)pyrrolidin-2-yl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00850] A ((2R)pyrrolidin-2-yl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00851] 468.2 A {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6-(3- pyrrolino[3,4-d]1,3-thiazol-2- yl)pyridazin-3-yl)amine [00852] 383.1 D 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- (methylsulfonyl)-3- pyrrolino[3,4-d]1,3-thiazole [00853] 461.1 D N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-hydroxyacetamide [00854] 429.1 A 2-[({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)amino]acetamide [00855] 428.1 B ((2S)-5-oxopyrrolidin-2-yl)-N-({2- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00856] 482.1 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-hydroxy-2- methylpropanamide [00857] 457.1 A N-((3S)pyrrolidin-3-yl){2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00858] 454.3 A N-((3R)pyrrolidin-3-yl){2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}carboxamide [00859] 454.3 A 2-[2-(6-{[1-(3-fluoro(2-pyridyl))- isopropyl]amino}pyridazin-3-yl)- 1,3-thiazol-5-yl]acetamide [00860] 373.2 D ((3S)morpholin-3-yl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00861] 484.3 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)pyrazol-5- ylcarboxamide [00862] 465.3 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)imidazol-2- ylcarboxamide [00863] 465.3 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)pyrazol-4- ylcarboxamide [00864] 465.3 A ((4S)-2-oxoimidazolidin-4-yl)-N- ({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00865] 483.3 A ((3S)-6-oxo(3-piperidyl))-N-({2- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00866] 496.3 A 2H-1,2,3-triazol-4-yl-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00867] 466.3 A (2S)-2-amino-N-({2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-3- hydroxypropanamide [00868] 458.3 A (2R)-2-amino-N-({2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-3- hydroxypropanamide [00869] 458.3 A ((2S)-4-acetylpiperazin-2-yl)-N- ({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00870] 525.3 A [(2S)-4-(methylsulfonyl)piperazin- 2-yl]-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00871] 562.3 A ((3S)morpholin-3-yl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00872] 484.2 A 1H-1,2,4-triazol-5-yl-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00873] 466.2 A ((2R)-6-oxo(2-piperidyl))-N-({2- [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00874] 495.2 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)imidazol-5- ylcarboxamide [00875] 465.2 A 2-amino-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-methylpropanamide [00876] 456.2 A (2S)-2-amino-N-({2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)propanamide [00877] 442.2 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)(2-hydroxyimidazol- 5-yl)carboxamide [00878] 481.2 A (2S)-2-amino-N-({2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-3-hydroxy-3- methylbutanamide [00879] 486.3 A (2R)-2-amino-N-({2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)propanamide [00880] 442.2 A ((3R)-1,1-dioxo(1,4- thiazaperhydroin-3-yl))-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00881] 532.1 A ((2S)-4,4-difluoropyrrolidin-2-yl)- N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00882] 504.2 A tert-butyl (2S)-4,4-difluoro-2-[N- ({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carbamoyl]pyrrolidine- carboxylate [00883] 604.2 B ((2S)-4,4-difluoro-1- formylpyrrolidin-2-yl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00884] 532.1 A ((2R,4R)-4-fluoropyrrolidin-2-yl)- N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00885] 486.1 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-methylpropanamide [00886] 441.3 A 4-fluoro-3-(6-{[1-(3-fluoro(2- pyridyl))- isopropyl]amino}pyridazin-3- yl)benzamide [00887] 370.2 B amino-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)amide [00888] 414.1 A ((3S)-1,1-dioxo(1,4- thiazaperhydroin-3-yl))-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00889] 532.3 A N-({2-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)acetamide [00890] 431.3 B N-({2-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)acetamide [00891] 431.2 B ((2S)pyrrolidin-2-yl)-N-{[2-(6- {[2-(3-fluoro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)(1,3-thiazol-5- yl)]methyl}carboxamide [00892] 456.3 B 2-(6-{[1-(3-chloro(2-pyridyl))- isopropyl]amino}pyridazin-3-yl)- 1,3-thiazole-5-carboxamide [00893] 375.2 B 4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [00894] 414.3 B 4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]benzenecarbonitrile [00895] 396.3 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4- hydroxybenzamide [00896] 412.3 B 4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoic acid [00897] 415.3 A 3-(6-{[2-(3-chloro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)benzamide [00898] 382.2 A 3-(6-{[2-(3-chloro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)-4-fluorobenzamide [00899] 400.3 A N-((2R)-2,3-dihydroxypropyl){4- fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00900] 488.3 A N-((3R)pyrrolidin-3-yl){4-fluoro- 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00901] 483.3 B N-((3S)pyrrolidin-3-yl){4-fluoro- 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00902] 483.3 B [6-(3-(2H-1,2,3,4-tetraazol-5- yl)phenyl)pyridazin-3-yl]{[3- fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00903] 421.1 A 3-(6-{[2-(3-chloro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)benzenecarbonitrile [00904] 364.2 B 3-(6-{[2-(3-chloro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)-4-fluorobenzenecarbonitrile [00905] 382.2 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazole- 5-sulfonamide [00906] 421.2 B (aminocyclopropyl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00907] 454.2 A (N-{1-[N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carbamoyl]- isopropyl}carbamoyloxy)ethyl 2- methylpropanoate [00908] 614.1 A 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoic acid [00909] 397.2 A 3-(6-{[(3-fluoro-1-(2- pyridyl)cyclobutyl)methyl]ami- no}pyridazin-3-yl)benzoic acid [00910] 379.3 A 3-(6-{[(3-fluoro-1-(2- pyridyl)cyclobutyl)methyl]ami- no}pyridazin-3-yl)benzoic acid [00911] 379.3 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]benzenecarbonitrile [00912] 378.2 B N-((2S)-2,3-dihydroxypropyl){4- fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00913] 488.3 A methyl 4-fluoro-3-[6-({[3-fluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoate [00914] 429.3 B {4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methylcarboxamide [00915] 428.3 A {4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- (methylethyl)carboxamide [00916] 456.3 A methyl 3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoate [00917] 411.3 B methylethyl 4-fluoro-3-[6-({[3- fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoate [00918] 457.3 B 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]imidazo[2,1-b]1,3-thiazoline- 3-carboxamide [00919] 424.1 A 6-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]imidazo[2,1-b]1,3-thiazoline- 3-carboxylic acid [00920] 425.1 A 6-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]imidazo[2,1-b]1,3-thiazoline- 3-carboxamide [00921] 442.1 A N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl){3- [benzylamino]oxetan-3- yl}carboxamide [00922] 560.2 A 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]benzenesulfonamide [00923] 432.2 B {5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1H-indazol-3- yl)}(methylsulfonyl)amine [00924] 486.3 A {[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6- [3-(methylamino)(1H-indazol-5- yl)]pyridazin-3-yl}amine [00925] 422.3 A {6-[3-(ethylamino)(1H-indazol-5- yl)]pyridazin-3-yl}{[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [00926] 434.3 A [6-(3-amino(1H-indazol-5- yl))pyridazin-3-yl]{[3-fluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [00927] 408.3 A ethyl 2-fluoro-5-[6-({[3-fluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoate [00928] 443.3 C 2-fluoro-5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzoic acid [00929] 415.3 B 2-{4-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}acetamide [00930] 410.1 B methyl 2-{4-fluoro-3-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}acetate [00931] 425.1 B N-({4-fluoro-3-[6-({[3-fluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}methyl)acetamide [00932] 442.4 B N-({3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}methyl)acetamide [00933] 424.3 B {2-fluoro-5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methylcarboxamide [00934] 428.3 C N-ethyl{2-fluoro-5-[6-({[3-fluoro- 1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00935] 442.3 C methyl 5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- (methylamino)benzoate [00936] 440.3 B ethyl 5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- (methylamino)benzoate [00937] 454.3 A {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}methan- 1-ol [00938] 383.2 B 2-[2-(6-{[2-(3-chloro(2-pyridyl))- 2-methylpropyl]amino}pyridazin- 3-yl)-1,3-thiazol-5-yl]acetamide [00939] 403.2 B 2-amino-N-{[2-(6-{[2-(3-chloro(2- pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)(1,3-thiazol-5-yl)]methyl}-2- methylpropanamide [00940] 460.1 A ((2S)azetidin-2-yl)-N-({2-[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00941] 454.1 A ethyl 2-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-4- yl}acetate [00942] 428.1 C 2-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-4- yl}acetamide [00943] 399.2 D 6-(6-{[1-(3-chloro(2-pyridyl))- isopropyl]amino}pyridazin-3- yl)imidazo[2,1-b]1,3-thiazoline- 3-carboxamide [00944] 414.1 B 6-(6-{[2-(3-chloro(2-pyridyl))-2- methylpropyl]amino}pyridazin-3- yl)imidazo[2,1-b]1,3-thiazoline-3- carboxamide [00945] 428.1 A 6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazine-3-carboxamide [00946] 302.2 D 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-2-methylpropanenitrile [00947] 409.1 D 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-2-methylpropanamide [00948] 427.1 D 3-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}propanamide [00949] 413.1 B 3-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}propanoic acid [00950] 414.1 B methyl 3-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}propanoate [00951] 428.1 B 6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazine-3-carboxylic acid [00952] 303.2 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N- methylcarboxamide [00953] 316.2 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N,N- dimethylcarboxamide [00954] 330.3 D 2-amino-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-methyl-N- methylpropanamide [00955] 470.2 A 2-{2-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}acetamide [00956] 417.1 B 2-{2-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}acetic acid [00957] 418.1 B 2-[2-(6-{[1-(3-chloro(2-pyridyl))- isopropyl]amino}pyridazin-3-yl)- 1,3-thiazol-5-yl]acetamide [00958] 389.1 D (3-aminooxetan-3-yl)-N-({2-[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)carboxamide [00959] 470.1 A {3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methylcarboxamide [00960] 392.3 B {4-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methylcarboxamide [00961] 410.3 A N-({5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-2- yl}methyl)acetamide [00962] 413.3 B N-({4-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-2- yl}methyl)acetamide [00963] 413.3 D 2-{2-[6-({[1-(3-chloro(2-pyridyl))- 3- fluorocyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}acetamide [00964] 433.2 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methylcarboxamide [00965] 410.1 A 2-{2-[6-({[(3-chloro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}acetamide [00966] 415.3 A 2-{2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}acetic acid [00967] 400.3 B 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-methylacetamide [00968] 413.3 B 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N,N-dimethylacetamide [00969] 427.3 B [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-isoxazol-3- ylcarboxamide [00970] 369.2 B [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(1,3-oxazol- 2-yl)carboxamide [00971] 369.2 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(1,3-thiazol- 2-yl)carboxamide [00972] 385.2 A [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(1,3,4- thiadiazol-2-yl)carboxamide [00973] 386.2 B [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-imidazol-2- ylcarboxamide [00974] 368.3 C N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-methyl-2- (methylamino)propanamide [00975] 470.3 A [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(1- methylpyrazol-3-yl)carboxamide [00976] 382.1 C N-(1H-1,2,4-triazol-5-yl)[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [00977] 369.3 D N-(4-cyanoimidazol-5-yl)[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [00978] 393.3 C N-(4-cyanopyrazol-5-yl)[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [00979] 393.3 B ethyl 4-{[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1-methylimidazole-2-carboxylate [00980] 454.3 D ethyl 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1,3-oxazole-4-carboxylate [00981] 441.3 D N-((3S)-2-oxopyrrolidin-3-yl)[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [00982] 385.3 D N-((3R)-2-oxopyrrolidin-3-yl)[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [00983] 385.3 D N-ethyl{4-fluoro-3-[6-({[3-fluoro- 1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00984] 442.3 B N-(2-fluoroethyl){4-fluoro-3-[6- ({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00985] 460.3 B N-(2,2-difluoroethyl){4-fluoro-3- [6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [00986] 478.3 B {4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- (2,2,2-trifluoroethyl)carboxamide [00987] 496.3 B {4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N,N- dimethylcarboxamide [00988] 442.3 B 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4- hydroxybenzoic acid [00989] 395.2 C 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]carbonylamino}cyclopentane- carboxamide [00990] 413.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-[(5- oxopyrrolidin-2- yl)methyl]carboxamide [00991] 399.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(2-oxo(3- piperidyl))carboxamide [00992] 399.3 D 4-{[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1-methylimidazole-2-carboxamide [00993] 425.3 D 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}amino)pyr- idazin-3-yl]carbonylamino}-1,3- oxazole-4-carboxamide [00994] 412.3 D {3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)pyr- idazin-3-yl]-4-hydroxyphenyl}-N- methylcarboxamide [00995] 408.3 B 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4- hydroxybenzamide [00996] 394.3 B 5-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3- yl]carbonylamino}pyrazole-4- carboxamide [00997] 411.3 C 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxypyridine-3-carbonitrile [00998] 391.1 D 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxypyridine-3-carboxamide [00999] 409.2 C 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- oxohydropyridine-3-carboxylic acid [01000] 396.1 D 5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- oxohydropyridine-3-carboxamide [01001] 395.1 C [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(pyrazol-5- ylmethyl)carboxamide [01002] 382.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-[(1- methylpyrazol-5- yl)methyl]carboxamide [01003] 396.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-[(1- methylpyrazol-3- yl)methyl]carboxamide [01004] 396.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-[(5- oxopyrrolidin-3- yl)methyl]carboxamide [01005] 385.3 D N-((3S)-6-oxo(3-piperidyl))[6-({[(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [01006] 399.3 D N-((3R)-6-oxo(3-piperidyl))[6- ({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [01007] 399.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(2- pyridylmethyl)carboxamide [01008] 393.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(3- pyridylmethyl)carboxamide [01009] 393.3 C [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(4- pyridylmethyl)carboxamide [01010] 393.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-(1,3-thiazol-2- ylmethyl)carboxamide [01011] 399.3 D [6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-N-methyl-N-(1,3- thiazol-2-ylmethyl)carboxamide [01012] 413.2 D ethyl 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1,3-thiazole-5-carboxylate [01013] 457.3 D methyl 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1,3-thiazole-4-carboxylate [01014] 443.2 B ethyl 2-(2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1,3-thiazol-4-yl)acetate [01015] 471.3 A 5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-hydroxybenzoic acid [01016] 413.1 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-[2- hydroxy-1- (hydroxymethyl)ethyl]carboxamide [01017] 470.2 B {5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxyphenyl}-N- methylcarboxamide [01018] 426.1 B 5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01019] 412.1 A {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4- hydroxyphenyl}-N- methylcarboxamide [01020] 426.2 B 2-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1,3-thiazole-4-carboxamide [01021] 428.1 A {5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](2-thienyl)}-N- methylcarboxamide [01022] 398.1 B 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4,5,6- trihydrocyclopenta[1,2-d]1,3- thiazole-4-carboxamide [01023] 425.3 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4,5,6- trihydrocyclopenta[1,2-d]1,3- thiazole-4-carboxylic acid [01024] 426.3 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6- (4,5,6,7-tetrahydro-1,3- thiazolo[5,4-c]pyridin-2- yl)pyridazin-3-yl)amine [01025] 397.5 D N-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](4,5,6- trihydrocyclopenta[2,3-d]1,3- thiazol-4-yl)}methoxycarboxamide [01026] 455.1 D 2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4,5,6,7- tetrahydro-1,3- thiazolo[5,4-c]pyridine-5- carboxamide [01027] 440.1 D 5-acetyl-2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4,5,6,7- tetrahydro-1,3- thiazolo[5,4-c]pyridine [01028] 439.3 D 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- (methylsulfonyl)-4,5,6,7- tetrahydro-1,3- thiazolo[5,4-c]pyridine [01029] 475.3 D {5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxyphenyl}-N,N- dimethylcarboxamide [01030] 440.1 B 4-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoindolin-1-one [01031] 408.1 B 5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoindolin-1-one [01032] 408.1 C 6-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]isoindolin-1-one [01033] 408.1 B [6-(6-amino(4,5,6,7- tetrahydrobenzothiazol-2- yl))pyridazin-3-yl]{[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [01034] 411.5 D amino-N-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](4,5,6,7- tetrahydrobenzothiazol-6-yl)}amide [01035] 454.3 D N-{3-fluoro-4-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}(methylamino)carbox- amide [01036] 443.3 A N-{4-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- methyl(methylamino)carboxamide [01037] 439.3 D N-[4-(carbamoylmethyl)(1,3- thiazol-2-yl)][6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [01038] 442.1 A 2-(2-{[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]carbonylamino}(1,3-thiazol-4- yl))-N-methylacetamide [01039] 456.2 A 2-{2-[6-({[1-(3-chloro(2-pyridyl))-3- fluorocyclobutyl]methyl}amino)pyr- idazin-3-yl](1,3-thiazol-5-yl)}-N- methylacetamide [01040] 447.3 B 3-{6-[4-(3-fluoro(2-pyridyl))-2- azabicyclo[2.1.1]hex-2- yl]pyridazin-3-yl}-4- hydroxybenzamide [01041] 392.1 D ethyl 2-(5-{[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]carbonylamino}- 1,3,4-thiadiazol-2-yl)acetate [01042] 472.3 D N-[5-(carbamoylmethyl)(1,3,4- thiadiazol-2-yl)][6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]carboxamide [01043] 443.2 D N-{4-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}(methylamino)carbox- amide [01044] 425.3 A 2-{2-[6-({[(3-chloro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}-N-methylacetamide [01045] 429.2 A N-cyclopropyl{4-fluoro-3-[6- ({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01046] 454.3 A 5-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-8-hydro-3- pyrazolino[1,5-a]pyrimidin-7-one [01047] 392.1 B 7-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-hydro-4- imidazolino[1,2-a]pyrimidin-5-one [01048] 392.3 B {4-fluoro-5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxyphenyl}-N- methylcarboxamide [01049] 444.1 A 4-fluoro-5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01050] 430.1 A 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4-methyl-3- pyrazolin-5-one [01051] 355.1 D 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-4,4-dimethyl-2- pyrazolin-5-one [01052] 369.2 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6- benzylpyridazin-3-yl]amine [01053] 349.3 D 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)-4-methylpyridazin-3- yl]benzenecarbonitrile [01054] 374.1 C 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)-4-methylpyridazin-3- yl]benzamide [01055] 392.1 C N-cyclobutyl{4-fluoro-3-[6-({[3- fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01056] 468.3 A 4-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)-4-methylpyridazin-3- yl]benzamide [01057] 410.1 C N-(3,3-difluorocyclobutyl){4- fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01058] 504.3 A 4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01059] 430.0 A 2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)- 4-methylpyridazin-3-yl]-1,3- thiazole-5-carboxamide [01060] 399.1 A 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)- 5-methylpyridazin-3-yl]benzamide [01061] 392.1 D N-cyclopropyl{3-[6-({[3-fluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01062] 436.3 B [6-(2-aminopyrimidin-5- yl)pyridazin-3-yl]{[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}amine [01063] 370.1 B N-azetidin-3-yl{3-[6-({[3-fluoro-1- (3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01064] 451.2 B N-(1-acetylazetidin-3-yl){3-[6- ({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01065] 493.3 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-[1- (methylsulfonyl)azetidin-3- yl]carboxamide [01066] 529.3 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-(2- hydroxy-2- methylpropyl)carboxamide [01067] 468.3 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-(1- methylazetidin-3-yl)carboxamide [01068] 465.3 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- oxetan-3-ylcarboxamide [01069] 452.3 B 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)- 4-methylpyridazin-3-yl]-1,3- thiazol-5-yl}acetic acid [01070] 414.1 B {2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)- 4-methylpyridazin-3-yl]-1,3- thiazol-5-yl}methan-1-ol [01071] 386.1 B 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)- 4-methylpyridazin-3-yl](1,3- thiazol-5-yl)}-N-methylacetamide [01072] 427.2 B 2-{2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}amino)- 4-methylpyridazin-3-yl]-1,3- thiazol-5-yl}acetamide [01073] 413.1 B {4-fluoro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-(1- methylazetidin-3-yl)carboxamide [01074] 483.3 B N-(1-acetylazetidin-3-yl){4-fluoro- 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01075] 511.3 A {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-(3- hydroxycyclobutyl)carboxamide [01076] 466.3 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6-[5- (piperazinylmethyl)(1,3-thiazol-2- yl)]pyridazin-3-yl}amine [01077] 440.3 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6-[5- (morpholin-4-ylmethyl)(1,3-thiazol- 2-yl)]pyridazin-3-yl}amine [01078] 441.3 B 4-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)-1,4-thiazaperhydroine- 1,1-dione [01079] 489.3 D {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}(6-{5- [(4-methylpiperazinyl)methyl](1,3- thiazol-2-yl)}pyridazin-3-yl)amine [01080] 454.3 B {[(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(5- {[4-(2,2,2- trifluoroethyl)piperazinyl]meth- yl}(1,3-thiazol-2-yl))pyridazin-3- yl]amine [01081] 522.2 B 1-acetyl-4-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)piperazine [01082] 482.3 D 1-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-4- (methylsulfonyl)piperazine [01083] 518.3 D [(2S)-1-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)piperazin-2-yl]methan- 1-ol [01084] 470.3 B [(2R)-1-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)piperazin-2-yl]methan- 1-ol [01085] 470.3 C N-(2H-3,4,5,6-tetrahydropyran-4- yl){3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01086] 480.3 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N-(3- hydroxy-3- methylcyclobutyl)carboxamide [01087] 480.3 B N-((3S)oxolan-3-yl){3-[6-({[3- fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01088] 466.3 B N-((3R)oxolan-3-yl){3-[6-({[3- fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01089] 466.3 B N-((3S,4S)-4-hydroxy-1,1- dioxothiolan-3-yl){3-[6-({[3-fluoro- 1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01090] 530.3 B N-(1,1-dioxothiolan-3-yl){3-[6-({[3- fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01091] 514.3 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01092] 412.1 A 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01093] 394.2 A 5-amino-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]benzenecarbonitrile [01094] 393.1 A 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- (trifluoromethyl)benzamide [01095] 464.1 B 5-chloro-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [01096] 430.1 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- hydroxybenzamide [01097] 412.1 A 5-amino-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]benzamide [01098] 411.2 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxyphenyl}-N- methylcarboxamide [01099] 426.2 A 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzenecarbonitrile [01100] 394.1 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzenecarbonitrile [01101] 408.1 C 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzoic acid [01102] 413.1 C 5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzamide [01103] 426.1 B N-(1,1-dioxothietan-3-yl){3-[6- ({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3- yl]phenyl}carboxamide [01104] 500.3 B 4-fluoro-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01105] 412.1 A 4-fluoro-5-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzamide [01106] 412.1 A {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]phenyl}-N- [(hydroxycyclopropyl)methyl]car- boxamide [01107] 466.1 A {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- methylphenyl}-N- methylcarboxamide [01108] 424.1 B 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-5- methylbenzamide [01109] 410.0 B 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-hydroxy-5- methylbenzamide [01110] 408.2 B 3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-hydroxy-5- methylbenzenecarbonitrile [01111] 390.2 B 5-bromo-3-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxybenzenecarbonitrile [01112] 454.0 A 3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- methoxybenzamide [01113] 426.2 D {5-bromo-3-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2- hydroxyphenyl}-N- methylcarboxamide [01114] 507.0 B {3-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]-2-hydroxy-5- methylphenyl}-N- methylcarboxamide [01115] 440.2 B methyl 5-[6-({[3-fluoro-1-(3- fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]indole-2- carboxylate [01116] 450.2 A 5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]indole-2- carboxamide [01117] 435.2 A 5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]indole-2- carboxylic acid [01118] 436.2 B {5-[6-({[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl]indol-2-yl}-N- methylcarboxamide [01119] 449.1 A [6-(6-amino(3-pyridyl))pyridazin-3- yl]{[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [01120] 369.3 A {[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}{6-[6- (methylamino)(3- pyridyl)]pyridazin-3-yl}amine [01121] 383.3 B {6-[6-(cyclopropylamino)(3- pyridyl)]pyridazin-3-yl}{[3-fluoro- 1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [01122] 409.3 D {6-[6-amino-5-(trifluoromethyl)(3- pyridyl)]pyridazin-3-yl}{[3-fluoro- 1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [01123] 437.0 B [N-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)carbamoyl]methyl acetate [01124] 470.1 A [N-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)carbamoyl]methyl (2S)- 2-amino-3-methylbutanoate [01125] 528.2 A [N-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)carbamoyl]methyl (2S)- 2-aminopropanoate [01126] 500.2 A {[3-fluoro-1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}[6-(6- methoxy-5-methyl(3- pyridyl))pyridazin-3-yl]amine [01127] 398.3 D [6-(6-amino-5-methyl(3- pyridyl))pyridazin-3-yl]{[3-fluoro- 1-(3-fluoro(2- pyridyl))cyclobutyl]methyl}amine [01128] 383.3 B (2S)-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-hydroxypropanamide [01129] 443.1 A (2R)-N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-hydroxypropanamide [01130] 443.1 A 2-[({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)amino]ethan-1-ol [01131] 415.1 B N-({2-[6-({[(3-fluoro(2- pyridyl))cyclobutyl]methyl}ami- no)pyridazin-3-yl](1,3-thiazol-5- yl)}methyl)-2-hydroxy-N- methylacetamide [01132] 443.1 B [N-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)carbamoyl]methyl (2S)- 2-((2S)-2- aminopropanoylamino)propanoate [01133] 571.1 A [N-({2-[6-({[(3-fluoro-2- pyridyl)cyclobutyl]methyl}ami- no)pyridazin-3-yl]-1,3-thiazol-5- yl}methyl)carbamoyl]methyl (2S)- 2-((2S)-2-amino-3- methylbutanoylamino)-3- methylbutanoate [01134] 627.3 A

[0410] While the present invention has been described with reference to the specific embodiments described herein, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, modifications may be made to adapt a particular situation, material, composition of matter and/or process to the objective, spirit and scope of the present invention. All such modifications are intended to be within the scope of the claims appended hereto.