Isoquinoline potassium channel inhibitors

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 6 H 5 ,

R 1 is selected from the group consisting of

—(CH 2 ) 2 OH, —(CH 2 ) 2 Cl, —CH 3 , hydrogen, —(CH 2 ) 2 N(CH 3 ) 2 , —CH 2 CH(OCH 2 CH 3 ) 2 , —(CH 2 ) 3 CH 3 , —(CH 2 ) 2 NHC(CH 3 ) 3 , —(CH 2 ) 2 N(CH 2 CH 3 ) 2 , —(CH 2 ) 2 NHCH(CH 3 ) 2 , —(CH 2 ) 2 NH(CH 2 )C(CH 3 ) 3 , —(CH 2 ) 2 NH(CH 2 ) 2 NHC(O)CH 3 , —CH 2 CH(OH)CH 2 OH, c(C 3 H 5 ), —CH 2 CHCH 2 , —(CH 2 ) 2 N(CH 3 )(CH 2 ) 2 OCH 3 , —(CH 2 ) 2 N(CH 3 )(CH 2 ) 2 OH, —(CH 2 ) 2 NH(CH 2 )OCH 3 , —CH 2 CF 3 , —CH 2 CHCH 2 , —(CH 2 ) 2 OH, —(CH 2 ) 2 NH(CH 2 ) 2 OH, —(CH 2 ) 3 OH, —CH 2 CH(OH)CH 2 N(CH 3 ) 2 , —CH 2 CH(NH 2 )CH 2 OH, —CH 2 CH(N(CH 3 ) 2 )CH 2 OH, —CH 2 CH(OH)CH 2 OCH(CH 3 ) 2 , —CH 2 C(O)OCH 2 CH 3 , —CH 2 CH(OH)CH 2 OCH 2 CH 3 , —CH 2 CH(OH)CH 2 OCH 3 , —CH 2 CH(OH)CH 2 CH 3 , —CH 2 CH(OH)CH 3 , —CH 2 C(OH)(CH 2 ) 2 , —CH 2 C(O)OH, —CH(CH 3 )C(O)OCH 3 ,

R 2 and R 8 are independently selected from:

1) hydrogen,

2) halogen,

3) NO 2 ,

4) CN,

5) CR 43 ═C(R 44 R 45 ),

6) C≡CR 43 ,

7) (CR e R f ) p OR 43 ,

8) (CR e R f ) p N(R 43 R 44 ),

9) (CR e R f ) p C(O)R 43 ,

10) (CR e R f ) p C(O)OR 43 ,

11) (CR e R f ) p R 43 ,

12) (CR e R f ) p S(O) 0-2 R 60 ,

13) (CR e R f ) p S(O) 0-2 N(R 43 R 44 ),

14) OS(O) 0-2 R 60 ,

15) N(R 43 )C(O)R 44 ,

16) N(R 43 )S(O) 0-2 R 60 ,

17) (CR e R f ) p N(R 43 )R 60 ,

18) (CR e R f ) p N(R 43 )R 60 OR 44 ,

19) (CR e R f ) p N(R 43 )(CR g R h ) q C(O)N(R 44 R 45 ),

20) N(R 43 )(CR e R f ) p R 60 ,

21) N(R 43 )(CR e R f ) p N(R 44 R 45 ), and

22) (CR e R f ) p C(O)N(R 43 R 44 ),

wherein one of R 2 and R 8 represents —OCH 3 ,

R a , R b , R c , R d , R e , R f , R g , R h , R i , R j , R k and R l are independently selected from the group consisting of:

1) hydrogen,

2) C 1 -C 6 alkyl,

3) halogen,

4) aryl,

5) R 80 ,

6) C 3 -C 10 cycloalkyl, and

7) OR 4 ,

said alkyl, aryl, and cycloalkyl being unsubstituted, monosubstituted with R 7 , disubstituted with R 7 and R 15 , trisubstituted with R 7 , R 15 and R 16 , or tetrasubstituted with R 7 , R 15 , R 16 and R 17 ;

R 4 , R 40 , R 41 , R 42 , R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 , R 51 , and R 52 are independently selected from the group consisting of

1) hydrogen,

2) C 1 -C 6 alkyl,

3) C 3 -C 10 cycloalkyl,

4) aryl,

5) R 81 ,

6) CF 3 ,

7) C 2 -C 6 alkenyl, and

8) C 2 -C 6 alkynyl,

said alkyl, aryl, and cycloalkyl is unsubstituted, mono-substituted with R 18 , di-substituted with R 18 and R 19 , tri-substituted with R 18 , R 19 and R 20 , or tetra-substituted with R 18 , R 19 , R 20 and R 21 ;

R 6 , R 60 , R 61 , and R 62 are independently selected from the group consisting of

1) C 1 -C 6 alkyl,

2) aryl,

3) R 83 , and

4) C 3 -C 10 cycloalkyl;

said alkyl, aryl, and cycloalkyl is unsubstituted, mono-substituted with R 26 , di-substituted with R 26 and R 27 , tri-substituted with R 26 , R 27 and R 28 , or tetra-substituted with R 26 , R 27 , R 28 and R 29 ;

R 7 , R 15 , R 16 , R 17 , R 18 , R 19 , R 20 , R 21 , R 26 , R 27 , R 28 , and R 29 are independently selected from the group consisting of

1) C 1 -C 6 alkyl,

2) halogen,

3) OR 51 ,

4) CF 3 ,

5) aryl,

6) C 3 -C 10 cycloalkyl,

7) R 84 ,

8) S(O) 0-2 N(R 51 R 52 ),

9) C(O)OR 51 ,

10) C(O)R 51 ,

11) CN,

12) C(O)N(R 51 R 52 ),

13) N(R 51 )C(O)R 52 ,

14) S(O) 0-2 R 62 ,

15) NO 2 , and

16) N(R 51 R 52 );

wherein R 80 , R 81 , R 83 , and R 84 are independently selected from the group of heterocyclic rings consisting of

where R 85 is selected from the group consisting of hydrogen, NH 2 , NO 2 , and CH 3 ,

where R 86 is selected from the group consisting of hydrogen and —C(O)OC(CH 3 ) 3 ,

where R 87 is selected from the group consisting of hydrogen and H 2 OH,

wherein R 88 and R 89 are independently selected from the group consisting of hydrogen, CH 3 and CH 2 CH 3 , and

wherein R 90 is selected from the group consisting of hydrogen,

R 9 is selected from the group consisting of

—OCH 3 , —CH 3 , —CH 2 CH 3 , Cl, —SCH 3 , I, Br, F, CF 3 ,

—O(CH 2 ) 2 NH 2 , —OCH 2 C(O)OH, —CH 2 NH 2 , —CH(OH)CH 3 , —OH, —OCH 2 CF 3 ,

—OCH 2 CHCH 2 , —O(CH 2 ) 2 OCH 3 , —OCH 2 CH(OH)CH 2 OH, —CH(NH 2 )CH 3 , —OCH 2 F,

—O(CH 2 ) 2 CH 3 , —O(CH 2 ) 2 OCH 2 CH 3 , —OCH 2 C(O)OCH 2 CH 3 , —O(CH 2 ) 2 OH,

—O(CH 2 ) 3 OH, —OCHF 2 , —OCH 2 C(O)N(CH 3 ) 2 , —O(CH 2 ) 3 C(O)OCH 2 CH 3 , O(CH 2 ) 4 C(O)OCH 2 CH 3 ,

—OCHCH 2 , —O(CH 2 ) 2 N(CH 3 ) 2 , —O(CH 2 ) 3 N(CH 3 ) 2 ,

—O(CH 2 ) 6 NH 2 , —C(CH 2 ) 3 C(O)OH, —O(CH 2 ) 4 C(O)OH, —O(CH 2 ) 4 NH 2 ,

—O(CH 2 ) 5 OC(O)CH 3 , —OCH 2 CN, —O(CH 2 ) 5 OH, —OC(O)CH 3 , —OSO 2 CH 3 ,

—OCH 2 C(O)C(CH 3 ) 3 ,

or R 9 and R 10 , together with the atoms to which they are attached, form the ring,

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.

2. A method of treating a condition in a mammal, the treatment of which is effected or facilitated by K v 1.5 inhibition, which comprises administering a compound of claim 1 in an amount that is effective at inhibiting K v 1.5 wherein the condition is cardiac arrhythmia.

3. A method of claim 2 , wherein the cardiac arrythmia is selected from the group consisting of atrial flutter, atrial arrhythmia and supraventricular tachycardia.

4. A method of claim 3 , wherein the cardiac arrythmia is atrial fibrillation.

5. A method of treating cardiac arrythmia comprising administering a compound of claim 1 with a compound selected from one of the classes of compounds consisting of antiarrhythmic agents having Kv 1.5 blocking activity, ACE inhibitors, angiotensin II antagonists, cardiac glycosides, L-type calcium channel blockers, T-type calcium channel blockers, selective and nonselective beta blockers, endothelin antagonists, thrombin inhibitors, aspirin, nonselective NSAIDs, warfarin, factor Xa inhibitors, low molecular weight heparin, unfractionated heparin, clopidogrel, ticlopidine, IIb/IIIa receptor antagonists, 5HT receptor antagonists, integrin receptor antagonists, thromboxane receptor antagonists, TAFI inhibitors and P2T receptor antagonists.

6. A pharmaceutical formulation comprising a pharmaceutically acceptable carrier and the compound of claim 1 or a pharmaceutically acceptable crystal form or hydrate thereof.

7. A pharmaceutical composition made by combining the compound of claim 1 and a pharmaceutically acceptable carrier.