THIOPHENE BASED APYRASE INHIBITORS

20260116872 · 2026-04-30

Inventors

Cpc classification

International classification

Abstract

Disclosed herein are apyrase inhibitors of Formula (I):

##STR00001##

Also disclosed herein are methods for using the disclosed inhibitors, including in methods for protecting crops from pests. In one aspect the apyrase inhibitors are useful for enhancing the activity of pesticides for the protection of crops from pathogens and to support crop yield.

Claims

1. A method for inhibiting apyrase, comprising contacting the apyrase with a compound of the formula ##STR00230## or an agriculturally acceptable salt, solvate and/or N-oxide thereof, wherein Z.sup.1 and Z.sup.2 are each independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl; or Z.sup.1 together with Z.sup.2 and the atoms to which Z.sup.1 and Z.sup.2 are attached, forms a 5- or 6-membered ring optionally substituted with one or more of R.sup.a; wherein the 5- or 6-membered ring is optionally a heterocyclyl ring with one or more heteroatom groups selected from O, N, N(R.sup.e), S, S(O), SO.sub.2; R.sup.1 is independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl, optionally substituted with one or more R.sup.a; R.sup.2 is selected from hydrogen and C.sub.1-6 alkyl; X is (CR.sup.aR.sup.b).sub.nY; Y is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.8, R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; S(O)R.sup.8, S(O).sub.2R.sup.8, N(R.sup.d)S(O).sub.2R.sup.8, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, C(O)OR.sup.8, C(O)R.sup.8, OC(O)R.sup.8, C(O)NR.sup.cR.sup.c, NR.sup.cR.sup.c, N(R.sup.d)C(O)R.sup.8, N(R.sup.d)C(O)OR.sup.8, N(R.sup.d)C(O)NR.sup.cR.sup.c, SR.sup.8, (CH.sub.2).sub.mR.sup.8, OC(O)(CH.sub.2).sub.mC(O)R.sup.8, CHR.sup.cR.sup.c; R.sup.8 is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, CH.sub.2R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; each R.sup.a is independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 haloalkyl, C.sub.3-8 cycloalkyl, C.sub.6-10 aryl, C.sub.5-10 heteroaryl, C.sub.6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl; R.sup.b is independently selected from the group consisting of O, OR.sup.a, halogen, C.sub.1-3 haloalkyloxy, OCF.sub.3, S, SR.sup.d, =NR.sup.d, =NOR.sup.d, NR.sup.cR.sup.c, SF.sub.5, halogen, CF.sub.3, CN, NO.sub.2, S(O)R.sup.d, S(O).sub.2R.sup.d, S(O).sub.2OR.sup.d, N(H)S(O).sub.2R.sup.d, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, OS(O).sub.2NR.sup.cR.sup.c, C(O)R.sup.d, C(O)OR.sup.d, C(O)NR.sup.cR.sup.c, C(NH)NR.sup.cR.sup.c, C(NR.sup.a)NR.sup.cR.sup.c, C(NOH)R.sup.a, C(NOH)NR.sup.cR.sup.c, OC(O)R.sup.d, OC(O)OR.sup.d, OC(O)NR.sup.cR.sup.c, OC(NH)NR.sup.cR.sup.c, OC(NR.sup.a)NR.sup.cR.sup.c, [NHC(O)].sub.nR.sup.d, [NR.sup.aC(O)].sub.nR.sup.d, [NHC(O)].sub.nOR.sup.d, [NR.sup.aC(O)].sub.nOR.sup.d, [NHC(O)].sub.nNR.sup.cR.sup.c, [NR.sup.aC(O)].sub.nNR.sup.cR.sup.c, [NHC(NH)].sub.nNR.sup.cR.sup.c and [NR.sup.aC(NR.sup.a)].sub.nNR.sup.cR.sup.c; each R.sup.c is hydrogen, R.sup.8, or, alternatively, two R.sup.c are taken together with the atom to which they are bonded to form a 5 to 10-membered cycloalkyl or heterocyclylalkyl which may optionally be substituted with one or more of the same or different R.sup.e groups; each R.sup.d is independently hydrogen or C.sub.1-6 alkyl; each R.sup.e is independently R.sup.b or R.sup.d; each m is independently an integer from 0 to 2; and each n is independently an integer from 0 to 2; provided that the compound is not ##STR00231##

2. The method of claim 1, wherein the compound has the formula: ##STR00232##

3. The method of claim 1, wherein the compound has the formula: ##STR00233##

4. The method of claim 1, wherein Z.sup.1, Z.sup.2, or both are hydrogen.

5. The method of claim 1, wherein Z.sup.1, Z.sup.2, or both are C.sub.1-6 alkyl.

6. The method of claim 1, wherein Z.sup.1 together with Z.sup.2 forms a 6-membered ring.

7. The method of claim 6, wherein Z.sup.1 and Z.sup.2 together form an aliphatic ring.

8. The method of claim 6, wherein Z.sup.1 and Z.sup.2 together form a heteroaliphatic ring.

9. The method of claim 6, wherein Z.sup.1 and Z.sup.2 together form an aromatic ring.

10. The method of claim 6, wherein Z.sup.1 and Z.sup.2 together form a heteroaromatic ring.

11. The method of claim 1, wherein Z.sup.1 together with Z.sup.2 forms a ring selected from: ##STR00234##

12. The method of claim 1, wherein the compound has the formula: ##STR00235## ##STR00236##

13. The method of claim 12 wherein Y is selected from the group consisting of ##STR00237## ##STR00238## ##STR00239## ##STR00240## ##STR00241## ##STR00242## ##STR00243## ##STR00244##

14. The method of claim 1, wherein the compound is selected from the group consisting of: ethyl 2-(3-(N-(3-chlorophenyl)sulfamoyl)benzamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl pyrazine-2-carboxylate 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl picolinate ethyl 2-(2-(phenylamino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(cyclohexyl(methyl)amino)acetamido)-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethylisonicotinate 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl furan-2-carboxylate ethyl 2-(2-(4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(o-tolyloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(tert-butylamino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-((4-hydroxy-6-oxo-1-propyl-1,6-dihydropyrimidin-2-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 2-(1H-pyrazol-1-yl)nicotinate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl furan-2-carboxylate isopropyl 2-(2-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(quinolin-8-yloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-methoxyphenoxy)acetamido)thiophene-3-carboxylate isopropyl 2-(2-((4-oxo-4-(thiophen-2-yl)butanoyl)oxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-((5-oxo-4-propyl-4,5-dihydro-1H-1,2,4-triazol-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 2-(tert-butyl)-1,2,3,4-tetrahydroacridine-9-carboxylate ethyl 2-(2-cyclopentylacetamido)-4,5-dimethylthiophene-3-carboxylate isopropyl 2-(2-((5,7-dimethyl-[1,2,4]triazolo[4,3-a]pyrimidin-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(3-fluorophenoxy)acetamido)thiophene-3-carboxylate ethyl 2-(2-(thieno[2,3-d]pyrimidin-4-ylthio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-phenylacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-(2-((methylsulfonyl)methyl)-1H-benzo[d]imidazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(benzo[d]oxazol-2-ylthio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-((4-(2-methoxyphenyl)-4H-1,2,4-triazol-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-((3-(4-methyl-2-oxothiazol-3(2H)-yl)propanoyl)oxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(3-bromoisonicotinamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-((5-amino-4H-1,2,4-triazol-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(naphthalen-2-yloxy)acetamido)thiophene-3-carboxylate isopropyl 2-(2-((1-(3-fluorophenyl)cyclopentane-1-carbonyl)oxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-(6,7-dimethoxy-4-oxoquinazolin-3(4H)-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(5-((4-chloro-3,5-dimethyl-1H-pyrazol-1-yl)methyl)furan-2-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-((4-amino-5-(p-tolyl)-4H-1,2,4-triazol-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 6-methyl-2-(5-methylpyrazine-2-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((4-fluorophenyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 6,6-dimethyl-2-(2-(methylsulfonyl)propanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(methyl(phenyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(2-(1H-pyrazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-cyanoacetamido)-4,5-dimethylthiophene-3-carboxylate isopropyl 2-(1-methyl-1H-1,2,3-triazole-5-carboxamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(2-(4-oxopyrazolo[1,5-d][1,2,4]triazin-5(4H)-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(2-ethoxyacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 4,5-dimethyl-2-(2-(phenylthio)acetamido)thiophene-3-carboxylate isopropyl 2-(2-((4-methoxybenzyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate oxalic acid salt of isopropyl 2-(2-((3-hydroxypropyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(ethoxycarbonyl)-4,5-dimethylthiophen-2-yl)amino)-2-oxoethyl 5-methylisoxazole-4-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 6-oxo-1,4,5,6-tetrahydropyridazine-3-carboxylate isopropyl 2-(2-((4-allyl-5-methyl-4H-1,2,4-triazol-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((2-methoxyphenyl)amino)acetamido)-4,5-dimethylthiophene-3-carboxylate ethyl 2-(2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-chlorophenoxy)acetamido)-4,5-dimethylthiophene-3-carboxylate ethyl 2-(2-(3-cyanophenoxy)acetamido)thiophene-3-carboxylate ethyl 2-(2-((5-amino-1,3,4-thiadiazol-2-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 4,5-dimethyl-2-(3-(phenylthio)propanamido)thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 5-methylpyrazine-2-carboxylate ethyl 2-(2-((1,3,4-thiadiazol-2-yl)thio)acetamido)thiophene-3-carboxylate ethyl 2-(2-(quinazolin-4-ylthio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(1-acetylpyrrolidine-3-carboxamido)-6,6-dimethyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 2,5-dimethylfuran-3-carboxylate oxalic acid salt of isopropyl 2-(2-(4-methylpiperazin-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(2-oxo-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-(4-(furan-2-carbonyl)piperazin-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate oxalic acid salt of isopropyl 2-(2-(ethylamino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 4,5-dimethyl-2-(2-(thiophen-2-yl)acetamido)thiophene-3-carboxylate isopropyl 2-(2-(2-(4-oxo-3,4-dihydrophthalazin-1-yl)acetoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-(1H-1,2,4-triazol-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(naphthalen-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(p-tolylamino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(adamantan-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((5-amino-4H-1,2,4-triazol-3-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(ethoxycarbonyl)-4,5-dimethylthiophen-2-yl)amino)-2-oxoethyl 5-methylfuran-2-carboxylate isopropyl 6-methyl-2-(2-(4-(4-nitrophenyl)piperazin-1-yl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(ethoxycarbonyl)-4,5-dimethylthiophen-2-yl)amino)-2-oxoethyl isonicotinate 1-(2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl)cyclopentane-1-carboxylic acid ethyl 2-(2-((1-methyl-1H-tetrazol-5-yl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 2-hydroxyquinoline-4-carboxylate ethyl 2-(2-([1,2,4]triazolo[4,3-a]pyridin-3-ylthio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(3-morpholinopropanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 4-((2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethoxy)carbonyl)pyridine 1-oxide ethyl 2-(3-(pyrrolidin-1-yl)propanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate oxalic acid salt 2-((3-(ethoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 5-methylfuran-2-carboxylate ethyl 2-(2-(1-methyl-3,4-dihydropyrrolo[1,2-a]pyrazin-2(1H)-yl)acetamido)thiophene-3-carboxylate ethyl 2-(2-(2,4-difluorophenoxy)acetamido)-4,5-dimethylthiophene-3-carboxylate ethyl 2-acetamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-cyanoacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 4,5-dimethyl-2-(2-(m-tolylamino)acetamido)thiophene-3-carboxylate ethyl 2-(4-methoxy-4-oxobutanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-((3-(ethoxycarbonyl)-4,5-dimethylthiophen-2-yl)amino)-2-oxoethyl pyrazine-2-carboxylate ethyl 2-(2-(cycloheptylamino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((3,5-dimethylphenyl)amino)acetamido)-4,5-dimethylthiophene-3-carboxylate ethyl 2-(2-((2,6-difluorobenzoyl)oxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 4,5-dimethyl-2-(2-(o-tolyloxy)acetamido)thiophene-3-carboxylate 2-((3-(isopropoxycarbonyl)-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)amino)-2-oxoethyl 2-(allylamino)thiazole-4-carboxylate 2-((3-(ethoxycarbonyl)-4,5-dimethylthiophen-2-yl)amino)-2-oxoethyl picolinate ethyl 2-(2-(benzoyloxy)acetamido)-4,5-dimethylthiophene-3-carboxylate ethyl 2-(2-((4-(methoxycarbonyl)phenyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(benzylthio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((1-methyl-4,5-dihydro-1H-imidazol-2-yl)thio)acetamido)thiophene-3-carboxylate ethyl 2-(2-(azepan-1-yl)acetamido)-4,5-dimethylthiophene-3-carboxylate ethyl 2-(2-((4-chlorobenzyl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((1,3,4-thiadiazol-2-yl)thio)acetamido)-4,5-dimethylthiophene-3-carboxylate oxalic acid salt of ethyl 2-(2-(butylamino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((3-(trifluoromethyl)phenyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(2,6-dimethylmorpholino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)-N-methylacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate 2-(2-(4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid methyl 2-(2-(4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate isopropyl 2-(2-(4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate tert-butyl 2-(2-(4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)-2-methylpropanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((4-fluorophenyl)(methyl)amino)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((4-fluorophenyl)thio)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((4-fluorophenyl)sulfonyl)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(3-(4-fluorophenyl)propanamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-((((4-fluorobenzyl)oxy)carbonyl)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-chlorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-nitrophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(p-tolyloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-methoxyphenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(3-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(2-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(2,4-difluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(3-chloro-4-fluorophenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(benzo[d][1,3]dioxol-5-yloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-(trifluoromethoxy)phenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(3-(trifluoromethyl)phenoxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(pyridin-4-yloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(pyridin-3-yloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(pyridin-2-yloxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-((tetrahydro-2H-pyran-4-yl)oxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)acetamido)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)acetamido)benzo[b]thiophene-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)acetamido)-5-methyl-4-oxo-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-3-carboxylate ethyl 2-(2-(4-fluorophenoxy)acetamido)-4,7-dihydro-5H-thieno[2,3-c]thiopyran-3-carboxylate 6,6-dioxide ethyl 2-(2-phenoxyacetamido)-6,7-dihydro-4H-thieno[3,2-c]pyran-3-carboxylate ethyl 2-(2-phenoxyacetamido)benzo[b]thiophene-3-carboxylate ethyl 5-methyl-4-oxo-2-(2-phenoxyacetamido)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-3-carboxylate ethyl 2-(2-phenoxyacetamido)-6,7-dihydro-4H-thieno[3,2-c]thiopyran-3-carboxylate 5,5-dioxide ethyl 2-(2-((2-methylbenzoyl)oxy)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(pyrazine-2-carboxamido)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ethyl 2-(2-(N-methylpyrazine-2-carboxamido)acetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate; and ethyl 2-(2-(4-fluorophenoxy)acetamido)-4,7-dihydro-5H-thieno[2,3-c]thiopyran-3-carboxylate, or a combination thereof.

15. The method of claim 1, wherein contacting the apyrase comprises treating a crop with the compound.

16. The method of claim 15, further comprising treating the crop with a pesticide.

17. The method of claim 19, wherein the pesticide comprises a fungicide.

18. A composition, comprising a fungicide; a compound of the formula ##STR00245## or an agriculturally acceptable salt, solvate and/or N-oxide thereof, wherein Z.sup.1 and Z.sup.2 are each independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl; or Z.sup.1 together with Z.sup.2 and the atoms to which Z.sup.1 and Z.sup.2 are attached, forms a 5- or 6-membered ring optionally substituted with one or more of R.sup.a; wherein the 5- or 6-membered ring is optionally a heterocyclyl ring with one or more heteroatom groups selected from O, N, N(R.sup.e), S, S(O), SO.sub.2; R.sup.1 is independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl, optionally substituted with one or more R.sup.a; R.sup.2 is selected from hydrogen and C.sub.1-6 alkyl; X is (CR.sup.aR.sup.b).sub.nY; Y is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.8, R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; S(O)R.sup.8, S(O).sub.2R.sup.8, N(R.sup.d)S(O).sub.2R.sup.8, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, C(O)OR.sup.8, C(O)R.sup.8, OC(O)R.sup.8, C(O)NR.sup.cR.sup.c, NR.sup.cR.sup.c, N(R.sup.d)C(O)R.sup.8, N(R.sup.d)C(O)OR.sup.8, N(R.sup.d)C(O)NR.sup.cR.sup.c, SR.sup.8, (CH.sub.2).sub.mR.sup.8, OC(O)(CH.sub.2).sub.mC(O)R.sup.8, CHR.sup.cR.sup.c; R.sup.8 is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, CH.sub.2R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; each R.sup.a is independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 haloalkyl, C.sub.3-8 cycloalkyl, C.sub.6-10 aryl, C.sub.5-10 heteroaryl, C.sub.6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl; R.sup.b is independently selected from the group consisting of O, OR.sup.a, halogen, C.sub.1-3 haloalkyloxy, OCF.sub.3, S, SR.sup.d, =NR.sup.d, =NOR.sup.d, NR.sup.cR.sup.c, SF.sub.5, halogen, CF.sub.3, CN, NO.sub.2, S(O)R.sup.d, S(O).sub.2R.sup.d, S(O).sub.2OR.sup.d, N(H)S(O).sub.2R.sup.d, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, OS(O).sub.2NR.sup.cR.sup.c, C(O)R.sup.d, C(O)OR.sup.d, C(O)NR.sup.cR.sup.c, C(NH)NR.sup.cR.sup.c, C(NR.sup.a)NR.sup.cR.sup.c, C(NOH)R.sup.a, C(NOH)NR.sup.cR.sup.c, OC(O)R.sup.d, OC(O)OR.sup.d, OC(O)NR.sup.cR.sup.c, OC(NH)NR.sup.cR.sup.c, OC(NR.sup.a)NR.sup.cR.sup.c, [NHC(O)].sub.nR.sup.d, [NR.sup.aC(O)].sub.nR.sup.d, [NHC(O)].sub.nOR.sup.d, [NR.sup.aC(O)]&OR.sup.d, [NHC(O)].sub.nNR.sup.cR.sup.c, [NR.sup.aC(O)].sub.nNR.sup.cR.sup.c, [NHC(NH)].sub.nNR.sup.cR.sup.c and [NR.sup.aC(NR.sup.a)].sub.nNR.sup.cR.sup.c; each R.sup.c is hydrogen, R.sup.8, or, alternatively, two R.sup.c are taken together with the atom to which they are bonded to form a 5 to 10-membered cycloalkyl or heterocyclylalkyl which may optionally be substituted with one or more of the same or different R.sup.e groups; each R.sup.d is independently hydrogen or C.sub.1-6 alkyl; each R.sup.e is independently R.sup.b or R.sup.d; each m is independently an integer from 0 to 2; and each n is independently an integer from 0 to 2; and a phytologically acceptable carrier.

19. The composition of claim 18, wherein the composition comprises from about 1 to about 80 weight percent of the compound.

20. A pesticidal composition, comprising a pesticide; a compound of the formula ##STR00246## or an agriculturally acceptable salt, solvate and/or N-oxide thereof, wherein Z.sup.1 and Z.sup.2 are each independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl; or Z.sup.1 together with Z.sup.2 and the atoms to which Z.sup.1 and Z.sup.2 are attached, forms a 5- or 6-membered ring optionally substituted with one or more of R.sup.a; wherein the 5- or 6-membered ring is optionally a heterocyclyl ring with one or more heteroatom groups selected from O, N, N(R.sup.e), S, S(O), SO.sub.2; R.sup.1 is independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl, optionally substituted with one or more R.sup.a; R.sup.2 is selected from hydrogen and C.sub.1-6 alkyl; X is (CR.sup.aR.sup.b).sub.nY; Y is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.8, R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; S(O)R.sup.8, S(O).sub.2R.sup.8, N(R.sup.d)S(O).sub.2R.sup.8, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, C(O)OR.sup.8, C(O)R.sup.8, OC(O)R.sup.8, C(O)NR.sup.cR.sup.c, NR.sup.cR.sup.c, N(R.sup.d)C(O)R.sup.8, N(R.sup.d)C(O)OR.sup.8, N(R.sup.d)C(O)NR.sup.cR.sup.c, SR.sup.8, (CH.sub.2).sub.mR.sup.8, OC(O)(CH.sub.2).sub.mC(O)R.sup.8, CHR.sup.cR.sup.c; R.sup.8 is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, CH.sub.2R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; each R.sup.a is independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 haloalkyl, C.sub.3-8 cycloalkyl, C.sub.6-10 aryl, C.sub.5-10 heteroaryl, C.sub.6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl; R.sup.b is independently selected from the group consisting of O, OR.sup.a, halogen, C.sub.1-3 haloalkyloxy, OCF.sub.3, S, SR.sup.d, =NR.sup.d, =NOR.sup.d, NR.sup.cR.sup.c, SF.sub.5, halogen, CF.sub.3, CN, NO.sub.2, S(O)R.sup.d, S(O).sub.2R.sup.d, S(O).sub.2OR.sup.d, N(H)S(O).sub.2R.sup.d, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, OS(O).sub.2NR.sup.cR.sup.c, C(O)R.sup.d, C(O)OR.sup.d, C(O)NR.sup.cR.sup.c, C(NH)NR.sup.cR.sup.c, C(NR.sup.a)NR.sup.cR.sup.c, C(NOH)R.sup.a, C(NOH)NR.sup.cR.sup.c, OC(O)R.sup.d, OC(O)OR.sup.d, OC(O)NR.sup.cR.sup.c, OC(NH)NR.sup.cR.sup.c, OC(NR.sup.a)NR.sup.cR.sup.c, [NHC(O)].sub.nR.sup.d, [NR.sup.aC(O)].sub.nR.sup.d, [NHC(O)].sub.nOR.sup.d, [NR.sup.aC(O)].sub.nOR.sup.d, [NHC(O)].sub.nNR.sup.cR.sup.c, [NR.sup.aC(O)].sub.nNR.sup.cR.sup.c, [NHC(NH)].sub.nNR.sup.cR.sup.c and [NR.sup.aC(NR.sup.a)].sub.nNR.sup.cR.sup.c; each R.sup.c is hydrogen, R.sup.8, or, alternatively, two R.sup.c are taken together with the atom to which they are bonded to form a 5 to 10-membered cycloalkyl or heterocyclylalkyl which may optionally be substituted with one or more of the same or different R.sup.e groups; each R.sup.d is independently hydrogen or C.sub.1-6 alkyl; each R.sup.e is independently R.sup.b or R.sup.d; each m is independently an integer from 0 to 2; and each n is independently an integer from 0 to 2; and a phytologically acceptable carrier.

Description

DETAILED DESCRIPTION

I. Terms

[0008] The following explanations of terms and methods are provided to better describe the present disclosure and to guide those of ordinary skill in the art in the practice of the present disclosure. The singular forms a, an, and the refer to one or more than one, unless the context clearly dictates otherwise. The term or refers to a single element of stated alternative elements or a combination of two or more elements, unless the context clearly indicates otherwise. As used herein, comprises means includes. Thus, comprising A or B, means including A, B, or A and B, without excluding additional elements. All references, including patents and patent applications cited herein, are incorporated by reference in their entirety, unless otherwise specified.

[0009] Unless otherwise indicated, all numbers expressing quantities of components, molecular weights, percentages, temperatures, times, and so forth, as used in the specification or claims, are to be understood as being modified by the term about. Accordingly, unless otherwise indicated, implicitly or explicitly, the numerical parameters set forth are approximations that may depend on the desired properties sought and/or limits of detection under standard test conditions/methods. When directly and explicitly distinguishing embodiments from discussed prior art, the embodiment numbers are not approximates unless the word about is expressly recited.

[0010] Unless explained otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods, and examples are illustrative only and not intended to be limiting.

[0011] Administering refers to any suitable mode of administration, to control a fungal pathogen, including, treatment of an extant crop, seeds, soil or combination thereof.

[0012] Control with reference to a fungal pathogen, means block, inhibit and/or eradicate a fungal pathogen and/or prevent the fungal pathogen from damaging a crop. In one embodiment, control refers to the reduction of one or more fungi to undetectable levels, or to the reduction or suppression of a fungus to acceptable levels as determined by one of ordinary skill in the art (for example, a crop grower). Determinations of acceptable levels of fungus reduction are based on a number of factors, including to the crop, pathogen, severity of the pathogen, use restrictions, economic thresholds and other factors known to those of ordinary skill in the art.

[0013] As used herein, the terms enhancer and potentiator, refer to a compound or compounds disclosed herein that enhance the effects of a pesticide. Without limitation to theory the present enhancer compounds disclosed herein may function by blocking one or more pathways by which a pathogen, such as a fungal pathogen, evades toxicity, such as by detoxifying, sequestering or transporting a pesticide. In certain embodiment, the present compounds inhibit enzymatic apyrase activity which leads to the enhancement, accentuation or potentiation of a pesticide, such as an acaricide, antimicrobial, fungicide, herbicide, insecticide, molluscicide and/or nematocide. For example, when the enhancer or potentiator is used in conjunction with a fungicide, the combination of the potentiator and the fungicide enhances the fungicidal effect of the fungicide and/or renders a fungus that has become resistant to the fungicide susceptible to the fungicide as a result of the activity of the potentiator. Most often, these enhancers or potentiators do not themselves inhibit the growth of a fungus itself, nor do they have a detrimental effect on a living organism that is (or could be) infected with a fungus.

[0014] As used herein, the term inoculation refers to a method used to administer or apply an effective amount of a disclosed compound or formulation thereof to a target area of a field and/or plant. The inoculation method can be, but is not limited to, aerosol spray, pressure spray, direct watering, and dipping. Target areas of a plant could include, but are not limited to, the leaves, roots, stems, buds, flowers, fruit, seed of the plant, and bulbs of the plant including bulb, corm, rhizoma, stem tuber, root tuber and rhizophore. Inoculation can include a method wherein a plant is treated in one area (for example, the root zone or foliage) and another area of the plant becomes protected (for example, foliage is inoculated when a disclosed compound is applied in the root zone or new growth when applied to foliage).

[0015] As used herein, the terms wettable granule, water dispersible granule, and dispersible granule refer to a solid granular formulation prepared by a granulation process, optionally containing fine particles of polymer-associated active ingredient, or aggregates of the same, a wetting agent and/or a dispersant, and optionally an inert filler. Wettable granules can be stored as a formulation, and can be provided to the market and/or end user without further processing. In some embodiments, they can be placed in a water-soluble bag for ease of use by the end user. In practical application, wettable granules are prepared for application by the end user. The wettable granules are mixed with water in the end user's spray tank to the proper dilution for the particular application. Dilution can vary by crop, target pathogen, time of year, geography, local regulations, and intensity of infection or pathogen load among other factors. Once properly diluted, the solution can be applied by spraying.

[0016] As used herein, the terms wettable powder, water dispersible powder, and dispersible powder, refer to a solid powdered formulation that contains active ingredient, optionally associated with a polymer, or aggregates of the same, and optionally one or more of a dispersant, a wetting agent, and an inert filler. Wettable powders can be stored as a formulation, and can be provided to the market and/or end user without further processing. In some embodiments, they can be placed in a water-soluble bag for ease of use by the end user. In practical application, a wettable powder is prepared for application by the end user. The wettable powder is mixed with water in the end user's spray tank to the proper dilution for the particular application. Dilution can vary by crop, fungal pathogen, time of year, geography, local regulations, and intensity of fungal load, among other factors. Once properly diluted, the solution can be applied by spraying.

[0017] As used herein, the term high solids liquid suspension refers to a liquid formulation that contains fine particles of active ingredient, or fine polymer particles associated with active ingredient, or aggregates of the same, a wetting agent and/or a dispersant, an anti-freezing agent, optionally an anti-settling agent or thickener, optionally a preservative, and water or oil as a carrier. High solids liquid suspensions can be stored as a formulation, and can be provided to the market and/or end user without further processing. In practical application, high solids liquid suspensions are prepared for application by the end user. The high solids liquid suspensions are mixed with water or oil in the end user's spray tank to the proper dilution for the particular application. Dilution can vary by crop, fungal pathogen, time of year, geography, local regulations, and intensity of infection among other factors. Once properly diluted, the solution can be applied by spraying.

[0018] As used herein, the term phytologically acceptable refers to compositions, diluents, excipients, and/or carriers that are generally applicable for use with any part of a plant during any part of its life cycle, including but not limited to seeds, seedlings, plant cells, plants, or flowers. The compositions can be prepared according to procedures, methods and formulas that are known to those of skill in the agricultural arts. Following the teachings of the present disclosure the artist skilled in the agricultural and/or chemical arts can readily prepare a desired composition. Most commonly, the compounds disclosed herein can be formulated to be stored, and/or applied, as aqueous or non-aqueous suspensions or emulsions prepared neat or from concentrated formulations of the compositions. Alternatively the compounds disclosed herein can be formulated for use in aerosol-generating equipment for application to agricultural produce stored in sealed chambersan application method known as fogging. Water-soluble, water-suspendable or emulsifiable formulations comprising the presently disclosed compounds can also be converted into or formulated as solids (for example, wettable powders), which can then be diluted into a final formulation. In certain formulations, the compositions of the present disclosure can also be provided in growth media, such as in vitro media for growth of plant or other types of cells, in laboratory plant growth media, in soil, or for spraying on seeds, seedlings, roots, stems, stalks, leaves, flowers or the entire plant.

[0019] Compounds herein can include all stereoisomers, including E and Z isomers, enantiomers, diastereomers, mixtures, racemates, atropisomers, and tautomers of the illustrated structures.

[0020] Non-limiting examples of optional substituents include hydroxyl groups, sulfhydryl groups, halogens, amino groups, nitro groups, nitroso groups, cyano groups, azido groups, sulfoxide groups, sulfone groups, sulfonamide groups, carboxyl groups, carboxaldehyde groups, imine groups, alkyl groups, halo-alkyl groups, alkenyl groups, haloalkenyl groups, alkynyl groups, halo-alkynyl groups, alkoxy groups, aryl groups, aryloxy groups, aralkyl groups, arylalkoxy groups, heterocyclylalkyl groups, heteroaryl groups, cycloalkyl groups, acyl groups, acyloxy groups, carbamate groups, amide groups, ureido groups, epoxy groups, and ester groups.

[0021] Alkyl refers to an optionally substituted straight-chain, or optionally substituted branched-chain saturated hydrocarbon. Non-limiting examples of alkyl groups include straight, branched, and cyclic alkyl and alkylene groups. An alkyl group can be, for example, a C.sub.1, C.sub.2, C.sub.3, C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, C.sub.10, C.sub.11, C.sub.12, C.sub.13, C.sub.14, C.sub.15, C.sub.16, C.sub.17, C.sub.18, C.sub.19, C.sub.20, C.sub.21, C.sub.22, C.sub.23, C.sub.24, C.sub.25, C.sub.26, C.sub.27, C.sub.28, C.sub.29, C.sub.30, C.sub.31, C.sub.32, C.sub.33, C.sub.34, C.sub.35, C.sub.36, C.sub.37, C.sub.38, C.sub.39, C.sub.40, C.sub.41, C.sub.42, C.sub.43, C.sub.44, C.sub.45, C.sub.46, C.sub.47, C.sub.48, C.sub.49, or C.sub.50 group that is substituted or unsubstituted. In some cases alkyl refers to a group having from one to about ten carbon atoms, or from one to six carbon atoms, wherein an sp.sup.3-hybridized carbon of the alkyl residue is attached to the rest of the molecule by a single bond. Whenever it appears herein, a numerical range such as C.sub.1-6 alkyl means that the alkyl group consists of 1 carbon atom, 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms or 6 carbon atoms, although the present definition also covers the occurrence of the term alkyl where no numerical range is designated. In some embodiments, the alkyl is a C.sub.1-10 alkyl, a C.sub.1-9 alkyl, a C.sub.1-8 alkyl, a C.sub.1-7 alkyl, a C.sub.1-6 alkyl, a C.sub.1-5 alkyl, a C.sub.1-4 alkyl, a C.sub.1-3 alkyl, a C.sub.1-2 alkyl, or a C.sub.1 alkyl.

[0022] Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, tert-amyl, and hexyl, and longer alkyl groups, such as heptyl, octyl, and the like.

[0023] Non-limiting examples of straight alkyl groups include methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, and decyl.

[0024] Branched alkyl groups include any straight alkyl group substituted with any number of alkyl groups. Non-limiting examples of branched alkyl groups include isopropyl, isobutyl, sec-butyl, and t-butyl.

[0025] When a carbon number limit is given at the beginning of a term which itself comprises two terms, the carbon number limitation is understood as inclusive for both terms. For example, for the term C.sub.7-14arylalkyl, both the aryl and the alkyl portions of the term are included the carbon count, a maximum of 14 in this example, but additional substituent groups thereon are not included in the atom count unless they incorporate a carbon from the group's designated carbon count, as in the oxo example above. Likewise when an atom number limit is given, for example 6-14 membered heteroarylalkyl, both the heteroaryl and the alkyl portion are included the atom count limitation, but additional substituent groups thereon are not included in the atom count unless they incorporate a carbon from the group's designated carbon count. As an example, the alkyl portion of, e.g. C.sub.7-14arylalkyl is meant to include alkylene, alkylidene or alkylidyne, unless stated otherwise, e.g. as in the terms C.sub.7-14arylalkylene or C.sub.6-10aryl-CH.sub.2CH.sub.2.

[0026] Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, the alkyl is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, the alkyl is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, or OMe. In some embodiments, the alkyl is optionally substituted with halogen. Non-limiting examples of substituted alkyl groups includes hydroxymethyl, chloromethyl, trifluoromethyl, aminomethyl, 1-chloroethyl, 2-hydroxyethyl, 1,2-difluoroethyl, and 3-carboxypropyl.

[0027] Alkenyl refers to an optionally substituted straight-chain, or optionally substituted branched-chain hydrocarbon having one or more carbon-carbon double-bonds. The olefin or olefins of an alkenyl group can be, for example, E, Z, cis, trans, terminal, or exo-methylene. An alkenyl group can be, for example, a C.sub.2, C.sub.3, C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, C.sub.10, C.sub.11, C.sub.12, C.sub.13, C.sub.14, C.sub.15, C.sub.16, C.sub.17, C.sub.18, C.sub.19, C.sub.20, C.sub.21, C.sub.22, C.sub.23, C.sub.24, C.sub.25, C.sub.26, C.sub.27, C.sub.28, C.sub.29, C.sub.30, C.sub.31, C.sub.32, C.sub.33, C.sub.34, C.sub.35, C.sub.36, C.sub.37, C.sub.38, C.sub.39, C.sub.40, C.sub.41, C.sub.42, C.sub.43, C.sub.44, C.sub.45, C.sub.46, C.sub.47, C.sub.48, C.sub.49, or C.sub.50 group that is substituted or unsubstituted. Non-limiting examples of alkenyl and alkenylene groups include ethenyl, prop-1-en-1-yl, isopropenyl, but-1-en-4-yl; 2-chloroethenyl, 4-hydroxybuten-1-yl, 7-hydroxy-7-methyloct-4-en-2-yl, and 7-hydroxy-7-methyloct-3,5-dien-2-yl.

[0028] Whenever it appears herein, a numerical range such as C.sub.2-C.sub.6 alkenyl means that the alkenyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term alkenyl where no numerical range is designated. In some embodiments, the alkenyl is a C.sub.2-C.sub.10 alkenyl, a C.sub.2-C.sub.9 alkenyl, a C.sub.2-C.sub.8 alkenyl, a C.sub.2-C.sub.7 alkenyl, a C.sub.2-C.sub.6 alkenyl, a C.sub.2-C.sub.5 alkenyl, a C.sub.2-C.sub.4 alkenyl, a C.sub.2-C.sub.3 alkenyl, or a C.sub.2 alkenyl. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an alkenyl is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, an alkenyl is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, or OMe. In some embodiments, the alkenyl is optionally substituted with halogen.

[0029] Alkylene refers to straight, branched and cyclic (and combinations thereof) divalent radical consisting solely of carbon and hydrogen atoms, containing no unsaturation and having from one to ten carbon atoms, for example, methylene, ethylene, propylene, n-butylene and the like. Alkylene refers to to the same residues as alkyl, but having two points of attachment and, specifically, being fully saturated. Examples of alkylene include ethylene (CH.sub.2CH.sub.2), propylene (CH.sub.2CH.sub.2CH.sub.2), dimethylpropylene (CH.sub.2C(CH.sub.3).sub.2CH.sub.2), cyclohexan-1,4-diyl and the like. The term alkylidene and alkylidyne refer to straight, branched and cyclic (and combinations thereof) divalent radicals consisting solely of carbon and hydrogen atoms, and having at least one alkene or alkyne bond, respectively.

[0030] Alkynyl refers to an optionally substituted straight-chain or optionally substituted branched-chain hydrocarbon. The triple bond of an alkynyl group can be internal or terminal. An alkynyl or alkynylene group can be, for example, a C.sub.2, C.sub.3, C.sub.4, C.sub.5, C.sub.6, C.sub.7, C.sub.8, C.sub.9, C.sub.10, C.sub.11, C.sub.12, C.sub.13, C.sub.14, C.sub.15, C.sub.16, C.sub.17, C.sub.18, C.sub.19, C.sub.20, C.sub.21, C.sub.22, C.sub.23, C.sub.24, C.sub.25, C.sub.26, C.sub.27, C.sub.28, C.sub.29, C.sub.30, C.sub.31, C.sub.32, C.sub.33, C.sub.34, C.sub.35, C.sub.36, C.sub.37, C.sub.38, C.sub.39, C.sub.40, C.sub.41, C.sub.42, C.sub.43, C.sub.44, C.sub.45, C.sub.46, C.sub.47, C.sub.48, C.sub.49, or C.sub.50 group that is substituted or unsubstituted. Non-limiting examples of alkynyl groups include ethynyl, prop-2-yn-1-yl, prop-1-yn-1-yl, and 2-methyl-hex-4-yn-1-yl; 5-hydroxy-5-methylhex-3-yn-1-yl, 6-hydroxy-6-methylhept-3-yn-2-yl, and 5-hydroxy-5-ethylhept-3-yn-1-yl.

[0031] Whenever it appears herein, a numerical range such as C.sub.2-C.sub.6 alkynyl means that the alkynyl group may consist of 2 carbon atoms, 3 carbon atoms, 4 carbon atoms, 5 carbon atoms, or 6 carbon atoms, although the present definition also covers the occurrence of the term alkynyl where no numerical range is designated. In some embodiments, the alkynyl is a C.sub.2-C.sub.10 alkynyl, a C.sub.2-C.sub.9 alkynyl, a C.sub.2-C.sub.8 alkynyl, a C.sub.2-C.sub.7 alkynyl, a C.sub.2-C.sub.6 alkynyl, a C.sub.2-C.sub.5 alkynyl, a C.sub.2-C.sub.4 alkynyl, a C.sub.2-C.sub.3 alkynyl, or a C.sub.2 alkynyl. Unless stated otherwise specifically in the specification, an alkynyl group is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an alkynyl is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, an alkynyl is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, or OMe. In some embodiments, the alkynyl is optionally substituted with halogen.

[0032] A haloalkyl group can be any alkyl group substituted with any number of halogen atoms, for example, fluorine, chlorine, bromine, and iodine atoms. A halo-alkenyl group can be any alkenyl group substituted with any number of halogen atoms. A haloalkynyl group can be any alkynyl group substituted with any number of halogen atoms.

[0033] An alkoxy group can be, for example, an oxygen atom substituted with any alkyl, alkenyl, or alkynyl group. An ether or an ether group comprises an alkoxy group. Non-limiting examples of alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, and isobutoxy.

[0034] The term acyl refers to the groups HC(O), alkyl-C(O), cycloalkyl-C(O), cycloalkenyl-C(O), aryl-C(O), heteroaryl-C(O) and heterocyclyl-C(O) where alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl are as described herein. By way of example acyl groups include acetyl and benzoyl groups.

[0035] Alkoxy refers to a radical of the formula OR.sup.a where R.sup.a is an alkyl radical as defined. Unless stated otherwise specifically in the specification, an alkoxy group may be optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an alkoxy is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, an alkoxy is optionally substituted with oxo, halogen, CN, CF.sub.3, OH, or OMe. In some embodiments, the alkoxy is optionally substituted with halogen.

[0036] Aminoalkyl refers to an alkyl radical, as defined above, that is substituted by one or more amines. In some embodiments, the alkyl is substituted with one amine. In some embodiments, the alkyl is substituted with one, two, or three amines. Hydroxyalkyl include, for example, aminomethyl, aminoethyl, aminopropyl, aminobutyl, or aminopentyl. In some embodiments, the hydroxyalkyl is aminomethyl.

[0037] Aryl refers to a radical derived from a hydrocarbon ring system comprising hydrogen, 6 to 30 carbon atoms, and at least one aromatic ring. The aryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocyclylalkyl ring, the aryl is bonded through an aromatic ring atom) or bridged ring systems. In some embodiments, the aryl is a 6- to 10-membered aryl. In some embodiments, the aryl is a 6-membered aryl. Aryl radicals include, but are not limited to, aryl radicals derived from the hydrocarbon ring systems of anthrylene, naphthylene, phenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene. In some embodiments, the aryl is phenyl. Unless stated otherwise specifically in the specification, an aryl may be optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, an aryl is optionally substituted with halogen, methyl, ethyl, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, an aryl is optionally substituted with halogen, methyl, ethyl, CN, CF.sub.3, OH, or OMe. In some embodiments, the aryl is optionally substituted with halogen.

[0038] Arylalkyl or Aralkyl refers to a residue in which an aryl moiety is attached to a parent structure via one of an alkylene, alkylidene, or alkylidyne radical. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl and the like. When specified as optionally substituted, both the aryl, and the corresponding alkylene, alkylidene, or alkylidyne portion of an arylalkyl group can be optionally substituted. By way of example, C.sub.7-11arylalkyl refers to an arylalkyl limited to a total of eleven carbons, e.g., a phenylethyl, a phenylvinyl, a phenylpentyl and a naphthylmethyl are all examples of a C.sub.7-11arylalkyl group.

[0039] Cycloalkyl refers to a stable, partially or fully saturated, monocyclic or polycyclic carbocyclic ring, which may include fused (when fused with an aryl or a heteroaryl ring, the cycloalkyl is bonded through a non-aromatic ring atom), bridged, or spiro ring systems. Representative cycloalkyls include, but are not limited to, cycloalkyls having from three to fifteen carbon atoms (C.sub.3-C.sub.15 cycloalkyl), from three to ten carbon atoms (C.sub.3-C.sub.10 cycloalkyl), from three to eight carbon atoms (C.sub.3-C.sub.8 cycloalkyl), from three to six carbon atoms (C.sub.3-C.sub.6 cycloalkyl), from three to five carbon atoms (C.sub.3-C.sub.5 cycloalkyl), or three to four carbon atoms (C.sub.3-C.sub.4 cycloalkyl). In some embodiments, the cycloalkyl is a 3- to 6-membered cycloalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered cycloalkyl. Non-limiting examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl groups. Cycloalkyl groups also include fused-, bridged-, and spiro-bicycles and higher fused-, bridged-, and spiro-systems. A cycloalkyl group can be substituted with any number of straight, branched, or cyclic alkyl groups. Non-limiting examples of cyclic alkyl groups include cyclopropyl, 2-methyl-cycloprop-1-yl, cycloprop-2-en-1-yl, cyclobutyl, 2,3-dihydroxycyclobut-1-yl, cyclobut-2-en-1-yl, cyclopentyl, cyclopent-2-en-1-yl, cyclopenta-2,4-dien-1-yl, cyclohexyl, cyclohex-2-en-1-yl, cycloheptyl, cyclooctanyl, 2,5-dimethylcyclopent-1-yl, 3,5-dichlorocyclohex-1-yl, 4-hydroxycyclohex-1-yl, 3,3,5-trimethylcyclohex-1-yl, octahydropentalenyl, octahydro-1H-indenyl, 3a,4,5,6,7,7a-hexahydro-3H-inden-4-yl, decahydroazulenyl, bicyclo-[2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, 1,3-dimethyl[2.2.1]heptan-2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl. Monocyclic cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0040] Polycyclic cycloalkyls or carbocycles include, for example, adamantyl, norbornyl, decalinyl, bicyclo[3.3.0]octane, bicyclo[4.3.0]nonane, cis-decalin, trans-decalin, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.2]decane, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl.

[0041] Partially saturated cycloalkyls include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Unless stated otherwise specifically in the specification, a cycloalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, a cycloalkyl is optionally substituted with oxo, halogen, methyl, ethyl, CN, CF.sub.3, OH, or OMe. In some embodiments, the cycloalkyl is optionally substituted with halogen.

[0042] Deuteroalkyl refers to an alkyl radical, as defined above, that is substituted by one or more deuteriums. In some embodiments, the alkyl is substituted with one deuterium. In some embodiments, the alkyl is substituted with one, two, or three deuteriums. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six deuteriums. Deuteroalkyl include, for example, CD.sub.3, CH.sub.2D, CHD.sub.2, CH.sub.2CD.sub.3, CD.sub.2CD.sub.3, CHDCD.sub.3, CH.sub.2CH.sub.2D, or CH.sub.2CHD.sub.2. In some embodiments, the deuteroalkyl is CD.sub.3.

[0043] Haloalkyl refers to an alkyl radical, as defined above, that is substituted by one or more halogens. In some embodiments, the alkyl is substituted with one, two, or three halogens. In some embodiments, the alkyl is substituted with one, two, three, four, five, or six halogens. Haloalkyl include, for example, trifluoromethyl, difluoromethyl, fluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 1,2-difluoroethyl, 3-bromo-2-fluoropropyl, 1,2-dibromoethyl, and the like. In some embodiments, the haloalkyl is trifluoromethyl.

[0044] Halo or halogen refers to bromo, chloro, fluoro, or iodo. In some embodiments, halogen is fluoro or chloro. In some embodiments, halogen is fluoro.

[0045] Heteroalkyl refers to an alkyl group in which one or more skeletal atoms of the alkyl are selected from an atom other than carbon, e.g., oxygen, nitrogen (e.g., NH, N(alkyl)-), sulfur, or combinations thereof. A heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. In one aspect, a heteroalkyl is a C.sub.1-6 heteroalkyl wherein the heteroalkyl is comprised of 1 to 6 carbon atoms and one or more atoms other than carbon, e.g., oxygen, nitrogen (e.g. NH, N(alkyl)-), sulfur, or combinations thereof wherein the heteroalkyl is attached to the rest of the molecule at a carbon atom of the heteroalkyl. Examples of such heteroalkyl are, for example, CH.sub.2OCH.sub.3, CH.sub.2CH.sub.2OCH.sub.3, CH.sub.2CH.sub.2OCH.sub.2CH.sub.2OCH.sub.3, or CH(CH.sub.3)OCH.sub.3. Unless stated otherwise specifically in the specification, a heteroalkyl is optionally substituted for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, a heteroalkyl is optionally substituted with oxo, halogen, methyl, ethyl, CN, CF.sub.3, OH, or OMe. In some embodiments, the heteroalkyl is optionally substituted with halogen.

[0046] Hydroxyalkyl refers to an alkyl radical, as defined above, that is substituted by one or more hydroxyls. In some embodiments, the alkyl is substituted with one hydroxyl. In some embodiments, the alkyl is substituted with one, two, or three hydroxyls. Hydroxyalkyl include, for example, hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl, or hydroxypentyl. In some embodiments, the hydroxyalkyl is hydroxymethyl.

[0047] A heterocycle can be any ring containing a ring atom that is not carbon, for example, N, O, S, P, Si, B, or any other heteroatom. A heterocycle can be substituted with any number of substituents, for example, alkyl groups and halogen atoms. A heterocycle can be aromatic (heteroaryl) or non-aromatic. Non-limiting examples of heterocycles include pyrrole, pyrrolidine, pyridine, pyrimidine, pyrazine, pyridazine, piperidine, succinimide, maleimide, morpholine, imidazole, thiophene, furan, tetrahydrofuran, pyran, and tetrahydropyran.

[0048] Heterocyclyl refers to a stable 3- to 24-membered heterocycle. Non-limiting examples of heterocycles include: heterocyclic units having a single ring containing one or more heteroatoms, non-limiting examples of which include, diazirinyl, aziridinyl, azetidinyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolinyl, thiazolidinyl, isothiazolinyl, oxathiazolidinonyl, oxazolidinonyl, hydantoinyl, tetrahydrofuranyl, pyrrolidinyl, morpholinyl, piperazinyl, piperidinyl, dihydropyranyl, tetrahydropyranyl, piperidin-2-onyl, 2,3,4,5-tetrahydro-1H-azepinyl, 2,3-dihydro-1H-indole, and 1,2,3,4-tetrahydroquinoline; and ii) heterocyclic units having 2 or more rings one of which is a heterocyclic ring, non-limiting examples of which include hexahydro-1H-pyrrolizinyl, 3a,4,5,6,7,7a-hexahydro-1H-benzo[d]imidazolyl, 3a,4,5,6,7,7a-hexahydro-1H-indolyl, 1,2,3,4-tetrahydroquinolinyl, and decahydro-1H-cycloocta[b]pyrrolyl.

[0049] Heterocyclylalkyl refers to a heterocyclyl group that is partially or fully saturated. Accordingly, heterocyclylalkyl refers to a stable 3- to 24-membered partially or fully saturated ring radical comprising 2 to 23 carbon atoms and from one to 8 heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur. Unless stated otherwise specifically in the specification, the heterocyclylalkyl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with an aryl or a heteroaryl ring, the heterocyclylalkyl is bonded through a non-aromatic ring atom) or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heterocyclylalkyl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized.

[0050] Representative heterocyclylalkyls include, but are not limited to, heterocyclylalkyls having from two to fifteen carbon atoms (C.sub.2-C.sub.15 heterocyclylalkyl), from two to ten carbon atoms (C.sub.2-C.sub.10 heterocyclylalkyl), from two to eight carbon atoms (C.sub.2-C.sub.8 heterocyclylalkyl), from two to six carbon atoms (C.sub.2-C.sub.6 heterocyclylalkyl), from two to five carbon atoms (C.sub.2-C.sub.5 heterocyclylalkyl), or two to four carbon atoms (C.sub.2-C.sub.4 heterocyclylalkyl). In some embodiments, the heterocyclylalkyl is a 3- to 6-membered heterocyclylalkyl. In some embodiments, the cycloalkyl is a 5- to 6-membered heterocyclylalkyl. Examples of such heterocyclylalkyl radicals include, but are not limited to, aziridinyl, azetidinyl, dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, 1,3-dihydroisobenzofuran-1-yl, 3-oxo-1,3-dihydroisobenzofuran-1-yl, methyl-2-oxo-1,3-dioxol-4-yl, and 2-oxo-1,3-dioxol-4-yl. The term heterocyclylalkyl also includes all ring forms of the carbohydrates, including but not limited to, the monosaccharides, the disaccharides, and the oligosaccharides. It is understood that when referring to the number of carbon atoms in a heterocyclylalkyl, the number of carbon atoms in the heterocyclylalkyl is not the same as the total number of atoms (including the heteroatoms) that make up the heterocyclylalkyl (i.e. skeletal atoms of the heterocyclylalkyl ring). Unless stated otherwise specifically in the specification, a heterocyclylalkyl is optionally substituted, for example, with oxo, halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heterocyclylalkyl is optionally substituted with oxo, halogen, methyl, ethyl, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, a heterocyclylalkyl is optionally substituted with oxo, halogen, methyl, ethyl, CN, CF.sub.3, OH, or OMe. In some embodiments, the heterocyclylalkyl is optionally substituted with halogen.

[0051] Heteroaryl refers to a 5- to 14-membered ring system radical comprising hydrogen atoms, one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen, phosphorous, and sulfur, and at least one aromatic ring. The heteroaryl radical may be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include fused (when fused with a cycloalkyl or heterocyclylalkyl ring, the heteroaryl is bonded through an aromatic ring atom) or bridged ring systems; and the nitrogen, carbon, or sulfur atoms in the heteroaryl radical may be optionally oxidized; the nitrogen atom may be optionally quaternized. In some embodiments, the heteroaryl is a 5- to 10-membered heteroaryl. In some embodiments, the heteroaryl is a 5- to 6-membered heteroaryl. Examples include, but are not limited to, azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b][1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl, benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e., thienyl). Unless stated otherwise specifically in the specification, a heteroaryl is optionally substituted, for example, with halogen, amino, nitrile, nitro, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, aryl, cycloalkyl, heterocyclylalkyl, heteroaryl, and the like. In some embodiments, a heteroaryl is optionally substituted with halogen, methyl, ethyl, CN, CF.sub.3, OH, OMe, NH.sub.2, or NO.sub.2. In some embodiments, a heteroaryl is optionally substituted with halogen, methyl, ethyl, CN, CF.sub.3, OH, or OMe. In some embodiments, the heteroaryl is optionally substituted with halogen.

II. Compounds

[0052] In one embodiment enhancers of pesticidal activity disclosed herein include those having the Formulas set forth below. In one embodiment, the present disclosure provides a method for inhibiting apyrase, comprising contacting the apyrase with a compound of Formula (I)

##STR00003## [0053] or an agriculturally acceptable salt, solvate and/or N-oxide thereof, wherein [0054] Z.sup.1 and Z.sup.2 are each independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl; or Z.sup.1 together with Z.sup.2 and the atoms to which Z.sup.1 and Z.sup.2 are attached, forms a 5- or 6-membered ring optionally substituted with one or more of R.sup.a; [0055] wherein the 5- or 6-membered ring is optionally a heterocyclyl ring with one or more heteroatom groups selected from O, N, N(R.sup.e), S, S(O), SO.sub.2; [0056] R.sup.1 is independently selected from a group consisting of hydrogen, C.sub.1-6 alkyl, optionally substituted with one or more R.sup.a; [0057] R.sup.2 is selected from hydrogen and C.sub.1-6 alkyl; [0058] X is (CR.sup.aR.sup.b).sub.nY; [0059] Y is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.8, R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; S(O)R.sup.8, S(O).sub.2R.sup.8, N(R.sup.d)S(O).sub.2R.sup.8, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, C(O)OR.sup.8, C(O)R.sup.8, OC(O)R.sup.8, C(O)NR.sup.cR.sup.c, NR.sup.cR.sup.c, N(R.sup.d)C(O)R.sup.8, N(R.sup.d)C(O)OR.sup.8, N(R.sup.d)C(O)NR.sup.cR.sup.c, SR.sup.8, (CH.sub.2).sub.mR.sup.8, OC(O)(CH.sub.2).sub.mC(O)R.sup.8, CHR.sup.cR.sup.c; [0060] R.sup.8 is selected from the group consisting of R.sup.a, R.sup.b, R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, CH.sub.2R.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b, OR.sup.a substituted with one or more of the same or different R.sup.a or R.sup.b; [0061] each R.sup.a is independently selected from hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 haloalkyl, C.sub.3-8 cycloalkyl, C.sub.6-10 aryl, C.sub.5-10 heteroaryl, C.sub.6-16 arylalkyl, 2-6 membered heteroalkyl and 3-8 membered heterocyclylalkyl; [0062] R.sup.b is independently selected from the group consisting of O, OR.sup.a, halogen, C.sub.1-3 haloalkyloxy, OCF.sub.3, S, SR.sup.d, NR.sup.d, NOR.sup.d, NR.sup.cR.sup.c, SF.sub.5, halogen, CF.sub.3, CN, NO.sub.2, S(O)R.sup.d, S(O).sub.2R.sup.d, S(O).sub.2OR.sup.d, N(H)S(O).sub.2R.sup.d, S(O)NR.sup.cR.sup.c, S(O).sub.2NR.sup.cR.sup.c, OS(O)R.sup.d, OS(O).sub.2R.sup.d, OS(O).sub.2OR.sup.d, OS(O).sub.2NR.sup.cR.sup.c, C(O)R.sup.d, C(O)OR.sup.d, C(O)NR.sup.cR.sup.c, C(NH)NR.sup.cR.sup.c, C(NR.sup.a)NR.sup.cR.sup.c, C(NOH)R.sup.a, C(NOH)NR.sup.cR.sup.c, OC(O)R.sup.d, OC(O)OR.sup.d, OC(O)NR.sup.cR.sup.c, OC(NH)NR.sup.cR.sup.c, OC(NR.sup.a)NR.sup.cR.sup.c, [NHC(O)].sub.nR.sup.d, [NR.sup.aC(O)].sub.nR.sup.d, [NHC(O)].sub.nOR.sup.d, [NR.sup.aC(O)].sub.nOR.sup.d, [NHC(O)].sub.nNR.sup.cR.sup.c, [NR.sup.aC(O)].sub.nNR.sup.cR.sup.c, [NHC(NH)].sub.nNR.sup.cR.sup.c and [NR.sup.aC(NR.sup.a)].sub.nNR.sup.cR.sup.c; [0063] each R.sup.c is hydrogen, R.sup.8, or, alternatively, two R.sup.c are taken together with the atom to which they are bonded to form a 5 to 10-membered cycloalkyl or heterocyclylalkyl which may optionally be substituted with one or more of the same or different R.sup.e groups; [0064] each R.sup.d is independently hydrogen or C.sub.1-6 alkyl; [0065] each R.sup.e is independently R.sup.b or R.sup.d; [0066] each m is independently an integer from 0 to 2; and [0067] each n is independently an integer from 0 to 2; provided that the compound is not

##STR00004##

[0068] In one embodiment of compounds according to Formula (I), R.sup.1 and R.sup.2 independently are selected from hydrogen and C.sub.1-6 alkyl. In certain embodiments, R.sup.1 is C.sub.1-6 alkyl optionally substituted with one or more R.sup.a. In one embodiment of such compounds according to Formula (I) R.sup.2 is hydrogen. In another embodiment of such compounds according to Formula (I) R.sup.1 is C.sub.1-6 alkyl optionally substituted with one or more R.sup.a and R.sup.2 is hydrogen.

[0069] In one embodiment of the enhancer compounds according to Formula (I), the compound has the formula:

##STR00005##

[0070] In another embodiment of the enhancer compounds according to Formula (I), the compound has the formula:

##STR00006##

[0071] In certain embodiments of enhancer compounds according to Formulas (I), (Ia) and (Ib) at least one of Z.sup.1 and Z.sup.2 is hydrogen, such as wherein Z.sup.1 is hydrogen, Z.sup.2 is hydrogen, or both Z.sup.1 and Z.sup.2 are hydrogen. In one embodiment, at least one of Z.sup.1 and Z.sup.2 is C.sub.1-6 alkyl, such as wherein Z.sup.1 is C.sub.1-6 alkyl, Z.sup.2 is C.sub.1-6 alkyl, or both Z.sup.1 and Z.sup.2 are the same or different C.sub.1-6 alkyl.

[0072] In other embodiments of enhancer compounds according to Formulas (I), (Ia) and (Ib), Z.sup.1 and Z.sup.2 together form a 5- or 6-membered aliphatic, aromatic, heteroaliphatic or heteroaromatic ring optionally substituted with one or more R.sup.8. In one embodiment, Z.sup.1 and Z.sup.2 together form a 5- or 6-membered aliphatic or heteroaliphatic ring. In certain embodiments, Z.sup.1 and Z.sup.2 together form an aliphatic ring, and in one such embodiment, enhancer compounds of Formula (I) have Formula (Ia1):

##STR00007##