Pharmaceutical compositions as inhibitors of dipeptidyl peptidase-IV (DPP-IV)
View Patent ↗The present invention relates to compounds of formula (I), which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, syndrome X, hyperinsulinemia, β-cell failure, obesity, satiety disorders, atherosclerosis, and various immunomodulatory diseases.
1. A compound of Formula (I)
or a therapeutically acceptable salt thereof, wherein
A is selected from the group consisting of
or therapeutically suitable salt, ester or prodrug, thereof, wherein
R 1 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, hydroxyalkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 2 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
or R 1 and R 2 , together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or unsubstituted pyridine;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 4 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxy cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
with the proviso that if R 1 and R 2 and the carbon atoms to which they are attached form a benzene ring, then R 4 is not carboxylic acid;
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl;
R 11 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 12 and R 13 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole;
R 14 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 21 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 22 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 23 and R 24 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole;
R 31 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 32 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 33 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 34 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 41 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 42 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 43 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 44 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 51 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 52 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
or R 51 and R 52 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole;
R 53 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and
R 62 , R 63 , R 64 and R 65 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl.
2. The compound according to claim 1 , wherein
R 1 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, hydroxyalkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 2 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 4 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl.
3. The compound according to claim 1 , wherein
R 1 is selected from the group consisting of halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, hydroxyalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 2 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 4 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl.
4. The compound according to claim 1 , wherein
R 1 is selected from the group consisting of halo, alkoxy, cyano, alkyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylsulfonyl, heteroaryl and hydroxyalkyl, wherein the heteroaryl is pyrazolyl;
R 2 is selected from the group consisting of hydrogen, halo and alkylsulfonyl;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, carboxy, carboxyalkoxy, alkylsulfonyl, heteroaryl and heterocycle, wherein the heteroaryl is tetrazolyl;
R 4 is selected from the group consisting of hydrogen, R a R b N—, alkoxycarbonyl, cyano, carboxy, alkylsulfonylNH and nitro; and
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl.
5. The compound according to claim 1 , wherein
R 1 and R 2 , together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or unsubstituted pyridine;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 4 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxy cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
with the proviso that if R 1 and R 2 and the carbon atoms to which they are attached form a benzene ring, then R 4 is not carboxylic acid; and
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl.
6. The compound according to claim 1 , wherein
R 1 and R 2 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyrimidine, pyrrole, thiazole, thiophene, triazine, 1,2,3-triazole or unsubstituted pyridine;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 4 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, alkoxy cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
with the proviso that if R 1 and R 2 and the carbon atoms to which they are attached form a benzene ring, then R 4 is not carboxylic acid; and
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl.
7. The compound according to claim 1 , wherein
R 1 and R 2 , together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, thiophene or unsubstituted pyridine;
R 3 is selected from the group consisting of hydrogen, halo, haloalkyl, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, carboxy, carboxyalkoxy, alkylsulfonyl, heteroaryl, heterocycle, wherein the heteroaryl is tetrazolyl;
R 4 is selected from the group consisting of hydrogen, R a R b N—, alkoxycarbonyl, alkoxy cyano, alkylsulfonylNH and nitro; and
R a and R b are independently selected from the group consisting of hydrogen, alkyl, aryl, alkenylcarbonyl, alkoxycarbonyl, alkoxyalkylcarbonyl, alkoxyalkoxycarbonyl, alkylcarbonyl, alkylsulfonyl, arylcarbonyl, arylalkylsulfonyl, arylsulfonyl, arylNHC(O), alkylsulfonyl, cycloalkylcarbonyl, heteroaryl, and heteroarylcarbonyl.
8. The compound according to claim 1 , wherein
R 11 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 12 and R 13 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole; and
R 14 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl.
9. The compound according to claim 1 , wherein
R 11 is selected from the group consisting of halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 12 and R 13 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole;
R 14 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl.
10. The compound according to claim 1 , wherein
R 11 is selected from the group consisting of halo, alkoxy, cyano and carboxy;
R 12 and R 13 together with the carbon atoms to which they are attached, form a substituted or unsubstituted benzene; and
R 14 is hydrogen.
11. The compound according to claim 1 , wherein
R 21 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 22 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 23 and R 24 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazolyl.
12. The compound according to claim 1 , wherein
R 21 is selected from the group consisting of halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 22 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 23 and R 24 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, naphthalene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazolyl.
13. The compound according to claim 1 , wherein
R 21 is selected from the group consisting of halo and carboxy;
R 22 is selected from the group consisting of hydrogen and halo; and
R 23 and R 24 together with the carbon atoms to which they are attached, form 1,3-dioxolane.
14. The compound according to claim 1 , wherein
R 31 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 32 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 33 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 34 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide.
15. The compound according to claim 1 , wherein
R 31 is selected from the group consisting of halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 32 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 33 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 34 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide.
16. The compound according to claim 1 , wherein
R 31 is halo;
R 32 is hydrogen;
R 33 is hydrogen,;
R 34 is hydrogen; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide.
17. The compound according to claim 1 , wherein
R 41 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 42 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 43 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 44 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide;
provided that exactly one of R 41 or R 44 is hydrogen.
18. The compound according to claim 1 , wherein
R 41 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 42 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazol:A, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 43 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 44 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide;
provided that exactly one of R 41 or R 44 is hydrogen.
19. The compound according to claim 1 , wherein
R 41 is selected from the group consisting of hydrogen, halo and carboxy;
R 42 is hydrogen;
R 43 is selected from the group consisting of hydrogen, halo, alkoxycarbonyl and carboxy;
R 44 is hydrogen; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide;
provided that exactly one of R 41 or R 44 is hydrogen.
20. The compound according to claim 1 , wherein
R 51 is selected from the group consisting of halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 52 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
or R 51 and R 52 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole;
R 53 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide.
21. The compound according to claim 1 , wherein
R 51 is selected from the group consisting of halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
R 52 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl,heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl;
or R 51 and R 52 together with the carbon atoms to which they are attached, form a substituted or unsubstituted heterocycle or a substituted or unsubstituted aryl, heteroaryl or cycloalkyl selected from the group consisting of benzene, cyclopentane, cyclohexane, cyclopentene, cyclohexene, furan, imidazole, isothiazole, isoxazole, 1,3-dioxolane, 1,2,3-oxadiazole, 1,2,5-oxadiazole, oxazole, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, thiazole, thiophene, triazine and 1,2,3-triazole;
R 53 is selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, R a R b N—, R a R b Ncarbonyl, alkoxy, alkoxycarbonyl, cyano, hydroxy, hydroxyalkyl, alkyl, alkenyl, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, nitro, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl; and wherein
the nitrogen of the pyridine group of A may be optionally substituted with an oxide.
22. The compound according to claim 1 , wherein
R 51 and R 52 together with the carbon atoms to which they are attached, form a benzene;
R 53 is hydrogen.
23. The compound according to claim 1 , wherein
R 62 , R 63 , R 64 and R 65 are each independently selected from the group consisting of hydrogen, halo, haloalkyl, haloalkoxy, haloalkylthio, R a R b N—, R a R b Ncarbonyl, R a R b Ncarbonylalkyl, R a R b Nsulfonyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, cyano, cyanoalkyl, hydroxy, hydroxyalkyl, alkyl, alkenyl, alkynyl, alkylthio, carboxy, carboxyalkyl, carboxyalkoxy, alkylcarbonyl, alkylsulfonyl, aryl, heteroaryl, heterocycle, cycloalkyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, formyl, formylalkyl, nitro, mercapto and mercaptoalkyl, wherein the heteroaryls are selected from the group consisting of furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1,2,3-oxadiazoyl, 1,2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl.
24. The compound according to claim 1 , wherein
R 62 , R 63 , R 64 and R 65 are hydrogen.
25. The compound according to claim 1 , that is selected from the group consisting of
(2S)-1-{(5R)-5-((2-chlorophenoxy)methyl)-L-prolyl}pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-(naphthalen-1-yloxymethyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((4-cyano-2-methoxyphenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((2-cyano-4-trifluoromethylphenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((2-chloro-4-cyanophenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((2-chloropyridyl-3-oxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((4-carboxy-2-methoxyphenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((4-carboxy-2-tert-butylphenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((4-carboxy-2-chlorophenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((4-carboxy-2-iso-propylphenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-([4-(tetrazol-5-yl)-2-chlorophenoxy]-methyl) L-prolyl}-pyrrolidin-2-carbonitrile;
(2S)-1-{(5R)-5-((5-carboxy-2-chlorophenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((5-carboxy-2-chloropyridyl-3-oxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-(5-carboxynaphthalen-1-yloxymethyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((4-carboxynaphthalen-1-yloxy)methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((5-carboxy-3-chloropyridyl-2-oxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-{(5R)-5-((5-carboxy-2-bromophenoxy)-methyl)-L-prolyl}-pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-methylphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-methoxyphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2,4-dichlorophenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[2-bromo-4-(trifluoromethyl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(4-bromo-2-methoxyphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-chloro-4-methoxyphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(4-bromo-2-chlorophenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[(4-chloro-1-naphthyl)oxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(quinolin-4-yloxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(quinolin-5-yloxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[4-bromo-2-(1H-pyrazol-3-yl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-tert-butylphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-tert-butyl-4-cyanophenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(4-bromo-2-tert-butylphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-isopropylphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
ethyl 3-tert-butyl-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoate;
{3-tert-butyl-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin--1 yl]carbonyl}pyrrolidin-2-yl)methoxy]phenoxy}acetic acid;
(2S)-1-[((2S,5R)-5-{[2-methoxy-4-(1H-tetraazol-5-yl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
3-tert-butyl-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzamide;
(2S)-1-[((2S,5R)-5-{[2-isopropyl-4-(1H-tetraazol-5-yl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]pyrrolidine-2-carboxylic acid;
(2S)-1-[((2S,5R)-5-{[4-(1-tert-butyl-1H-tetraazol-5-yl)-2-isopropylphenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[4-(1-tert-butyl-1H-tetraazol-5-yl)-2-chlorophenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
5-chloro-2-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoic acid;
{2-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}acetic acid;
3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-4-fluorobenzoic acid;
3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-4-isopropylbenzoic acid;
2-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-1-naphthoic acid;
3-chloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-N,N-dimethylbenzamide;
(2S)-1-[((2S,5R)-5-{[(2-chloro-1-oxidopyridin-3-yl)oxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(2-chloro-4-morpholin-4-ylphenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-({(2S,5R)-5-[(4-amino-2-chlorophenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
3-bromo-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoic acid;
6-chloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]nicotinic acid 1-oxide;
6-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-2-naphthoic acid;
(2S)-1-[((2S,5R)-5-{[2-chloro-4-(methylsulfonyl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[4-chloro-2-(hydroxymethyl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
5-chloro-6-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-2-naphthoic acid;
(2S)-1-[((2S,5R)-5-{[(6-chloro-1,3-benzodioxol-5-yl)oxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
N-{4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-1-naphthyl}methanesulfonamide;
(2S)-1-[((2S,5R)-5-{[2-bromo-4-(methylsulfonyl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[(6-bromo-1,3-benzodioxol-5-yl)oxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
2-chloro-N-{3-chloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}benzenesulfonamide;
N-{3-chloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}methanesulfonamide;
N-{3-chloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}acetamide;
(2S)-1-({(2S,5R)-5-[(1-benzothien-4-yloxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
(2S)-1-[((2S,5R)-5-{[4-bromo-2-(methylsulfonyl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
N-{3-bromo-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}acetamide;
N-{3-bromo-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}methanesulfonamide;
N-{3-bromo-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}benzenesulfonamide;
N-{3-bromo-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}-2-chlorobenzenesulfonamid;
methyl 2,3-dichloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoate;
3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-4-methoxybenzoic acid;
2,3-dichloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoic acid;
(2S)-1-({(2S,5R)-5-[(2,4-dichloro-5-nitrophenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
tert-butyl 2,3-dichloro-4-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoate;
ethyl 4-chloro-3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoate;
isopropyl 4-chloro-3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]benzoate;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}acetamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}acrylamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}benzamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}-2-methoxyacetamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}-2-(2-methoxyethoxy)acetamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}cyclopropanecarboxamide;
ethyl 2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenylcarbamate;
bis-[N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}]methanesulfonamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl)}-1-phenylmethanesulfonamide;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}-N′-phenylurea;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}-N′-(3,5-dimethoxyphenyl)urea;
N-{2,4-dichloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]phenyl}-N′-(4-nitrophenyl)urea;
(2S)-1-({(2S,5R)-5-[(5-amino-2,4-dichlorophenoxy)methyl]pyrrolidin-2-yl}carbonyl)pyrrolidine-2-carbonitrile;
isopropyl 6-chloro-5-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]nicotinate;
(2S)-1-[((2S,5R)-5-{[2-chloro-3-(methylsulfonyl)phenoxy]methyl}pyrrolidin-2-yl)carbonyl]pyrrolidine-2-carbonitrile;
ethyl 3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-4,5-difluorobenzoate;
3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-4,5-difluorobenzoic acid; and
tert-butyl 3-[((2R,5S)-5-{[(2S)-2-cyanopyrrolidin-1-yl]carbonyl}pyrrolidin-2-yl)methoxy]-4,5-difluorobenzoate.