Patent ID: 7763614
Filing Date: 2010-07-27
Classification: A61P,C04B,C07D

Abstract:
1. A compound of structural formula I: or a pharmaceutically acceptable salt, crystal form, or hydrate, wherein: A is selected from the group consisting of —C R —(CH R R R R R wherein R where R where R where R wherein R wherein R R —OCH —O(CH —OCH —O(CH —O(CH —OCHCH —O(CH —O(CH —OCH or R or a pharmaceutically acceptable salt thereof, wherein the compound is further selected from the group consisting of 6-methoxy-1-oxo-4-phenyl-2-[2-(5,6,7,8-tetrahydronaphthalen-1-ylamino)ethyl]-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-hydroxyethyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-chloroethyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-[2-(cyclopropylamino)ethyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-(4-methoxybenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2,6-dimethyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-ethyl-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-[2-(dimethylamino)ethyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-1-oxo-4-phenyl-2-[2-(4-pyrimidin-2-ylpiperazin-1-yl)ethyl]-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-{2-[4-(4-methoxyphenyl)piperazin-1-yl]ethyl}-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-{2-[4-(3-methoxyphenyl)piperazin-1-yl]ethyl}-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-{2-[4-(4-fluorophenyl)piperazin-1-yl]ethyl}-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-1-oxo-4-phenyl-2-(2-{4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,2-diethoxyethyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-4-(4-methylphenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-butyl-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, tert-butyl[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-carbamate, 6-methoxy-2-methyl-4-(2-methylphenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-4-(2-methylphenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(4-chlorophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-chlorophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(2-formylphenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-chloro-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-iodo-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 1-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]pyrrolidinium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-2-phenylbutan-1-aminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-2,2-diphenylethanaminium trifluoroacetate, 2-[2-(4-benzylpiperazin-1-yl)ethyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]indan-2-aminium trifluoroacetate, N-{[1-(4-chlorophenyl)cyclopropyl]methyl}-2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethanaminium trifluoroacetate, 6-methoxy-1-oxo-4-phenyl-2-{2-[(pyridin-4-ylmethyl)amino]ethyl}-1,2-dihydroisoquinoline-3-carbonitrile, tert-butyl4-[(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)methyl]-piperidine-1-carboxylate, 6-bromo-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, N-(3-cyano-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-6-yl)-N-hydroxyacetamide, N-(3-cyano-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-6-yl)-N- [(methylsulfonyl)oxy]methanesulfonamide, 4-[(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)methyl]piperidinium chloride, 6-fluoro-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]benzenaminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-4-phenylbutan-1-aminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-3-phenylpropan-1-aminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-2-methylpropan-2-aminium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-(cyclohexylmethyl)-ethanaminium trifluoroacetate, (1S)-N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-1-phenylethanaminium trifluoroacetate, 6-methoxy-1-oxo-4-phenyl-2-[2-(4-phenylpiperazin-1-yl)ethyl]-1,2-dihydroisoquinoline-3-carbonitrile, 1-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]piperidinium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-(diphenylmethyl)-ethanaminium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-N-methylethanaminium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N,N-diethylethanaminium trifluoroacetate, N-benzyl-2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethanaminium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-[(trans-4-{[(methylamino)-carbonyl]oxy}-1-phenylcyclohexyl)methyl]ethanaminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-2-methyl-2-phenylpropan-1-aminium trifluoroacetate, 2-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-1,2,3,4-tetrahydroisoquinolinium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-(2-thienylmethyl)-ethanaminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]indan-1-aminium trifluoroacetate, 6-methoxy-2-[2-(4-methylpiperazin-1-yl)ethyl]-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 4-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]morpholin-4-ium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]propan-2-aminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]cyclohexanaminium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-(cyclopropylmethyl)-ethanaminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-N-methylcyclohexanaminium trifluoroacetate, 2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-N-(2-phenylethyl)-ethanaminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]pyridin-2-aminium trifluoroacetate, (1R)-N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-1-phenylethanaminium trifluoroacetate, 6-methoxy-1-oxo-4-phenyl-2-{2-[(pyridin-3-ylmethyl)amino]ethyl}-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-{[3-(1H-imidazol-1-yl)propyl]amino}ethyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-3-(2-oxopyrrolidin-1-yl)propan-1-aminium trifluoroacetate, N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)ethyl]-3,3-dimethylbutan-1-aminium trifluoroacetate, 2-(acetylamino)-N-[2-(3-cyano-6-methoxy-1-oxo-4-phenylisoquinolin-2(1H)-yl)-ethyl]ethanaminium trifluoroacetate, 6-methoxy-2-methyl-1-oxo-4-pyridin-4-yl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-pyridin-3-yl-1,2-dihydroisoquinoline-3-carbonitrile, 5-methoxy-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, N-(3-cyano-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-6-yl)acetamide, N-(3-cyano-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-6-yl)methanesulfonamide, 2-methyl-1-oxo-4-phenyl-6-(trifluoromethyl)-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 7-methoxy-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-7-nitro-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-(2-aminoethoxy)-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, [(3-cyano-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-6-yl)oxy]acetic acid, 2[(ammoniooxy)methyl]-1-chloro-3-fluorobenzene chloride, 2-allyl-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-2-(2-morpholin-4-ylethyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-2-{2-[(2-methoxyethyl)(methyl)-amino]ethyl}-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2,5-dimethyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-2-{2-[(2-hydroxyethyl)(methyl)amino]ethyl}-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-2-{2-[(2-methoxyethyl)amino]ethyl}-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-(pyridin-2-ylmethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-6-(2-morpholin-4-ylethoxy)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-(2-piperidin-1-ylethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, 6-acetyl-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-(1-hydroxyethyl)-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-(piperidin-4-yloxy)-1,2-dihydroisoquinoline-3-carbonitrile, 6-(2,2-difluoro-2-pyridin-2-ylethoxy)-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-(pyrrolidin-3-yloxy)-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-1-oxo-2-(2,2,2-trifluoroethyl)-1,2-dihydroisoquinoline-3-carbonitrile, 4-(4-fluorophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 5,7-dibromo-4-(3-fluorophenyl)-6-hydroxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 5,7-dibromo-2-cyclopropyl-4-(3-fluorophenyl)-6-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 5-bromo-2-cyclopropyl-4-(3-fluorophenyl)-6-hydroxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-(2,2,2-trifluoroethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-6-(1-morpholin-4-ylethyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-6-[(1-oxidopyridin-2-yl)methoxy]-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-(allyloxy)-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-(2-methoxyethoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-[4-(trifluoromethyl)phenyl]-1,2-dihydroisoquinoline-3-carbonitrile, 2(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline- 3-carbonitrile, 2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(2,3-dihydroxypropoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-ethoxy-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 1-(3-cyano-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinolin-6-yl)ethanaminium trifluoroacetate, 5-bromo-6-methoxy-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 7-bromo-6-methoxy-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-thien-2-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(fluoromethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-thien-3-yl-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-2-(2-hydroxyethyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-2-{2-[(2-hydroxyethyl)amino]ethyl}-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-[(2s)-2,3-dihydroxypropyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-[(2r)-2,3-dihydroxypropyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 4-(2-fluorophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-4-(2-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-propoxy-1,2-dihydroisoquinoline-3-carbonitrile, 6-(benzyloxy)-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-2-(3-hydroxypropyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-[3-(dimethylamino)-2-hydroxypropyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-4-(4-nitrophenoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-4-(4-methoxyphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-amino-3-hydroxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-4-(2-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-[3-(trifluoromethyl)phenyl]-1,2-dihydroisoquinoline-3-carbonitrile, 4-[3,5-bis(trifluoromethyl)phenyl]-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-[2-(benzyloxy)ethoxy]-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-[2-(dimethylamino)-3-hydroxypropyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-[3-(dimethylamino)-2-hydroxypropyl]-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(2-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-hydroxy-3-isopropoxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-aminophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-4-(3-methylphenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3,5-dichlorophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-(tetrahydrofuran-2-ylmethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(cyclopropylmethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(2-ethoxyethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-[3-(benzyloxy)propoxy]-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(2,3-dihydro-1,4-benzodioxin-2-ylmethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-(tetrahydro-2H-pyran-2-ylmethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, ethyl {[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}acetate, 2-cyclopropyl-4-(3-fluorophenyl)-6-(2-hydroxyethoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(4-aminophenoxy)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-4-(3-methoxyphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-phenoxy-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-(3-hydroxypropoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(difluoromethoxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-6-morpholin-4-yl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-pyridin-4-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-pyridin-3-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N,N-dimethylacetamide, 2-cyclopropyl-4-(3-fluorophenyl)-6-(2-morpholin-4-yl-2-oxoethoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(4-cyanophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-cyanophenyl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(1,3-benzodioxol-5-yl)-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-6-(4-methylpiperazin-1-yl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-piperidin-1-yl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-(1h-pyrazol-3-yl)-1,2-dihydroisoquinoline-3-carbonitrile, 4-[4-(hydroxymethyl)phenyl]-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, ethyl [3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]acetate 2-[2-hydroxy-3-(1H-imidazol-1-yl)propyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-(3-furyl)-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-thiomorpholin-4-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-[(3-nitropyridin-2-yl)oxy]-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, ethyl 4-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}butanoate, ethyl 5-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}pentanoate, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-(vinyloxy)-1,2-dihydroisoquinoline-3-carbonitrile, 2-methyl-1-oxo-4-phenyl-6-pyridin-2-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(3-ethoxy-2-hydroxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-hydroxy-3-methoxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-hydroxybutyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2-hydroxypropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 6-[(3-aminopyridin-2-yl)oxy]-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, methyl 3-(3-cyano-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinolin-4-yl)benzoate, methyl 4-(3-cyano-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinolin-4-yl)benzoate, 2-cyclopropyl-6-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butoxy]-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-{[5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pentyl]oxy}-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-{[6-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)hexyl]oxy}-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N,N-dimethylethanaminium trifluoroacetate, 3-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N,N-dimethylpropan-1-aminium trifluoroacetate, 6-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}hexan-1-aminium trifluoroacetate, 4-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}butanoic acid, 4-ethynyl-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 5-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}pentanoic acid, 4-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}butan-1-aminium trifluoroacetate, 5-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}pentan-1-aminium trifluoroacetate, 6-(4-hydroxypiperidin-1-yl)-2-methyl-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-4-(3-chlorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 4-(3-fluorophenyl)-6-methoxy-1-oxo-2-[2-(3-oxo-4-phenylpiperazin-1-yl)ethyl]-1,2-dihydroisoquinoline-3-carbonitrile, 4-({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1h)-yl]ethyl}-amino)benzoic acid, 3-({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]ethyl}-amino)benzoic acid, 2-({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]ethyl}-amino)benzoic acid, 4-(3-chlorophenyl)-2-(2,3-dihydroxypropyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-6-(cyclopropyloxy)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-[(5-morpholin-4-yl-5-oxopentyl)oxy]-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-(4-morpholin-4-yl-4-oxobutoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 5-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}pentyl acetate, 2-cyclopropyl-4-(3-fluorophenyl)-6-(4-hydroxybutoxy)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 6-(cyanomethoxy)-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-4-(3-fluorophenyl)-6-[(5-hydroxypentyl)oxy]-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-6-methoxy-1-oxo-4-[3-(trifluoromethyl)phenyl]-1,2-dihydroisoquinoline-3-carbonitrile, 3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl morpholine-4-carboxylate, 2-{3-hydroxy-2-[(pyridin-3-ylmethyl)amino]propyl}-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl acetate, 4-(3-fluorophenyl)-2-{2-[(2-hydroxy-2,3-dihydro-1H-inden-1-yl)amino]ethyl}-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, methyl (2S)-({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]ethyl}-amino)(phenyl)ethanoate, methyl (2R)-({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1h)-yl]ethyl}-amino)(phenyl)ethanoate, 2-(2-hydroxy-2-methylpropyl)-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl benzoate, 3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl methanesulfonate, 6-methoxy-2-methyl-1-oxo-4-(phenylethynyl)-1,2-dihydroisoquinoline-3-carbonitrile, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}ethyl morpholine-4-carboxylate, 2-allyl-1-oxo-4-phenyl-6-thien-3-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-6-(3-furyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, 5-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}pentyl morpholine-4-carboxylate, 3-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}propyl morpholine-4-carboxylate, 4-(3-fluorophenyl)-2-(2-{[(1R)-2-hydroxy-1-phenylethyl]amino}-ethyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, ethyl ({2[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]ethyl}-amino)(phenyl)acetate, 2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-1-oxo-6-thien-3-yl-1,2-dihydroisoquinoline-3-carbonitrile, 6-(1-benzothien-3-yl)-2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, methyl [3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]acetate, 2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-6-(3-furyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-6-[2-(hydroxymethyl)thien-3-yl]-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, tert-butyl {[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}acetate, [3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]acetic acid, {[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}acetic acid, ({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]ethyl}amino)-(phenyl)acetic acid, 2-[3-hydroxy-2-(1h-1,2,3-triazol-1-yl)propyl]-6-methoxy-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbonitrile, methyl ({2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]ethyl}-amino)(pyridin-3-yl)acetate, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-(2-oxo-2-pyrrolidin-1-ylethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, methyl 2-[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1H)-yl]propanoate, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-(2-oxo-2-piperidin-1-ylethoxy)-1,2-dihydroisoquinoline-3-carbonitrile, N-benzyl-2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N-methylacetamide, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N-methoxy-N-methylacetamide, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N-(2-methoxyethyl)acetamide, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N-(3-methoxypropyl)acetamide, 2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-6-[2-oxo-2-(3-oxopiperazin-1-yl)ethoxy]-1,2-dihydroisoquinoline-3-carbonitrile, N-benzyl-2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}acetamide, 6-(2-azetidin-1-yl-2-oxoethoxy)-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}-N-(2-methoxyethyl)-N-methylacetamide, N,N-dibenzyl-2-{[3-cyano-2-cyclopropyl-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]oxy}acetamide, 2-allyl-6-methoxy-1-oxo-4-pyridin-2-yl-1,2-dihydroisoquinoline-3-carbonitrile, 6-methoxy-2-methyl-1-oxo-4-(1h-1,2,3-triazol-5-yl)-1,2-dihydroisoquinoline-3-carbonitrile, methyl {[(3-cyano-6-methoxy-2-methyl-1-oxo-1,2-dihydroisoquinolin-4-yl)oxy]sulfonyl}carbamate, 7-cyclopropyl-9-(3-fluorophenyl)-2-methyl-6-oxo-1,2,6,7-tetrahydrofuro [3,2-f]-isoquinoline-8-carbonitrile, 5-allyl-2-cyclopropyl-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-cyclopropyl-5-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-6-methoxy-1-oxo-4-pyridin-2-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-6-methoxy-1-oxo-4-pyridin-2-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-4-(3-fluorophenyl)-6-(6-methylpyridin-2-yl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-{[3-cyano-4-(3-fluorophenyl)-6-methoxy-1-oxoisoquinolin-2(1h)-yl]methyl}-1h-benzimidazol-1-ium chloride, 4-(3-fluorophenyl)-6-methoxy-1-oxo-2-{2-[(pyridin-2-ylmethyl)amino]ethyl}-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-4-(3-fluorophenyl)-1-oxo-6-(1H-pyrazol-4-yl)-1,2-dihydroisoquinoline-3-carbonitrile, 2-[2-allyl-3-cyano-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]-4-methylpyridinium trifluoroacetate, 2-[3-cyano-2-(2,3-dihydroxypropyl)-4-(3-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]-6-methylpyridinium trifluoroacetate, 4-(3-chlorophenyl)-2-{[(4S)-2,2-diethyl-1,3-dioxolan-4-yl]methyl}-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, 2-allyl-6-methoxy-1-oxo-4-pyridin-3-yl-1,2-dihydroisoquinoline-3-carbonitrile, 2-(2,3-dihydroxypropyl)-6-methoxy-4-(1-oxidopyridin-2-yl)-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile, and 4-(3-chlorophenyl)-2-[(2S)-2,3-dihydroxypropyl]-6-methoxy-1-oxo-1,2-dihydroisoquinoline-3-carbonitrile.