Isoquinolinone Rho kinase inhibitors

1. A compound of formula (I)

wherein:

R 1 is chosen from

C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, haloC 1-6 alkyl, aminoC 1-6 alkyl, hydroxyC 1-6 alkyl, aryl, heteroaryl, heteroarylC 1-6 alkyl, heterocyclyl, —C 1-3 alkylOaryl, —CH 2 OC(O)C 1-6 alkyl, (CH 2 ) 1-2 S(O) 0-2 C 1-6 alkyl, —(CH 2 ) 1-3 CO 2 C 1-6 alkyl, —(CH 2 ) 1-3 NHC 1-6 alkyl, —(CH 2 ) 1-3 NH C 1-6 alkylC 3-8 cycloalkyl, —(CH 2 ) 1-2 CN and —CH(R 3 )N(R 4 )(R 5 )

wherein:

R 3 is chosen from

H, C 1-6 alkyl, —(CH 2 ) 1-3 aryl and —(CH 2 ) 1-3 heteroaryl;

R 4 is chosen from

H, C 1-6 alkyl, C 3-12 cycloalkyl, C 3-7 cycloalkylC 1-6 alkyl, aryl, aryl(CH 2 ) 1-3 , heteroaryl(CH 2 ) 1-3 , C 1-3 alkylO(CH 2 ) 1-3 , tetrahydropyran-4-ylmethyl and (C 1-3 alkyl) 2 N(CH 2 ) 2-4 —;

and R 5 is chosen from

H and C 1-6 alkyl;

or R 4 and R 5 together with the nitrogen atom they are connected to may form a heterocyclyl group;

wherein each aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkylalkyl, cycloalkyl and heterocyclyl group is optionally substituted with 1-3 groups selected from

halogen, C 1-6 alkoxy, C 3-8 cycloalkyl, C 1-6 alkyl, —CN, —NO 2 , —OH, oxo, —CF 3 , —OCF 3 , —C 0-3 alkylCO 2 H, C 1-6 alkylCO 2 —, C 1-6 alkylsulfonylC 0-3 alkyl-, SO 2 C 1-6 alkylNR 6 R 7 , —C 0-3 alkylSO 2 NR 6 R 7 , —C 0-3 C(O)NR 6 R 7 , heteroaryl, heteroarylC 1-3 alkyl, heterocyclyl, heterocyclyISO 2 —, arylC 1-3 alkyl, aryloxy, arylthio and C 0-3 NR 6 R 7 ;

wherein each aryl and heteroaryl group is optionally substituted with 1-3 groups selected from

halogen, C 1-6 alkoxy, C 1-6 alkyl, —CN, —NO 2 , —OH, —CF 3 , —OCF 3 , —C(O)NR 8 R 9 , —SO 2 NR 8 R 9 , —SO 2 Me and amino optionally substituted by one or two C 1-6 alkyl groups or a C(O)C 1-6 alkyl group;

R 2 is chosen from H, halogen, C 1-6 alkoxy, —CN, —CF 3 and C 1-6 alkyl;

R 6 and R 7 are independently selected from H, C 1-6 alkyl, —C(O)C 1-6 alkyl and —C 1-6 alkylNH 2 ; or R 6 and R 7 , together with the nitrogen they are connected to may form a piperazine, piperidine or pyrrolidine ring;

R 8 and R 9 are independently selected from H and methyl;

R 10 is selected from H, Cl and F;

X is CH; and

Y is chosen from —NHC(O)—;

or a tautomer or a pharmaceutically acceptable salt of the compound of formula (I).

2. The compound of formula (I) according to claim 1 , wherein:

R 1 is chosen from

C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, phenyl, thienyl, pyridyl, isoxazolyl, pyrazolyl, thienylmethyl, piperidinyl, piperazinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, —CH 2 Ophenyl, —CH 2 OC(O)C 1-6 alkyl, —(CH 2 ) 1-2 S(O) 0-2 C 1-6 alkyl, —(CH 2 ) 1-3 CO 2 C 1-6 alkyl, —(CH 2 ) 1-3 NHC 1-6 alkyl, —(CH 2 ) 1-3 NHC 1-6 alkylC 3-8 cycloalkyl, —(CH 2 ) 1-3 CN and —CH(R 3 )N(R 4 )(R 5 )

wherein:

R 3 is chosen from

H, C 1-6 alkyl, benzyl, phenylethyl and pyridylmethyl;

R 4 is chosen from

H, C 1-6 alkyl, C 3-12 cycloalkyl, C 3-7 cycloalkylC 1-6 alkyl, phenyl, benzyl, thienylethyl, C 1-3 alkylO(CH 2 ) 1-3 , tetrahydropyran-4-ylmethyl and (C 1-3 ) 2 N(CH 2 ) 2-4 —;

and R 5 is chosen from

H and C 1-6 alkyl;

or R 4 and R 5 together with the nitrogen atom they are connected to may form a piperidine, piperazine or thiomorpholine group;

wherein each cycloalkyl, cycloalkylalkyl, phenyl, benzyl, phenylethyl, thienyl, pyridyl, isoxazolyl, pyrazolyl, thienylmethyl, piperidinyl, piperazinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, and thiomorpholinyl group is optionally substituted with 1-3 groups selected from

halogen, C 1-6 alkoxy, C 1-6 alkyl, —CN, —NO 2 , —OH, —CF 3 , —OCF 3 , C 1-6 alkylCO 2 —, C 1-6 alkylsulfonyl, pyrimidyl, pyridyl, morpholinyl, benzyl, phenyloxy, phenylthio and amino optionally substituted by one or two C 1-6 alkyl groups or a C(O)C 1-6 alkyl group;

wherein each phenyl, benzyl, pyrimidinyl and pyridyl group is optionally substituted with 1-3 groups selected from

halogen, C 1-6 alkoxy, C 1-6 alkyl, —CN, —NO 2 , —OH, —CF 3 , —OCF 3 , —C(O)NR 8 R 9 , —SO 2 NR 8 R 9 , —SO 2 Me and amino optionally substituted by one or two C 1-6 alkyl groups or a C(O)C 1-6 alkyl group;

R 2 is chosen from H, Br, Cl, —CN, —CF 3 and methyl;

R 8 and R 9 are independently selected from H and methyl; and

R 10 is selected from H, Cl and F;

or a tautomer or a pharmaceutically acceptable salt of the compound of formula (I).

3. The compound of formula (I) according to claim 1 , wherein:

R 1 is chosen from

cyclopentyl, cyclohexyl, phenyl, thienylmethyl, piperidinyl, pyrrolodinyl, —CH 2 Sphenyl and —CH(R 3 )N(R 4 )(R 5 )

wherein:

R 3 is chosen from

H, C 1-6 alkyl, benzyl and phenylethyl;

R 4 is chosen from

H, C 1-6 alkyl, C 3-12 cycloalkyl, C 3-7 cycloalkylmethyl, benzyl, thienylethyl, and tetrahydropyran-4-ylmethyl;

and R 5 is chosen from

H and methyl;

or R 4 and R 5 together with the nitrogen atom they are connected to may form a piperidine group;

wherein each cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, thienylmethyl, piperidinyl and pyrrolidinyl group is optionally substituted with 1-3 groups selected from halogen, C 1-6 alkoxy, C 1-6 alkyl, —CN, —NO 2 , —OH, —CF 3 , —OCF 3 , and amino optionally substituted by one or two C 1-6 alkyl groups or a C(O)C 1-6 alkyl group;

R 2 is chosen from H, Br and Cl; and

R 10 is H;

or a tautomer or a pharmaceutically acceptable salt of the compound of formula (I).

4. A compound selected from

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-(4-methyl-piperazin-1-yl)-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-(cyclohexylmethyl-amino)-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-thiomorpholin-4-yl-propionamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-(1,2,3,4-tetrahydro-naphthalen-1-ylamino)-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-(2-thiophen-2-yl-ethylamino)-propionamide;

(S)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-phenyl-propionamide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-phenyl-propionamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-[(tetrahydro-pyran-4-ylmethyl)-amino]-acetamide;

2-(Adamantan-1-ylamino)-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-[(pyridin-2-ylmethyl)-amino]-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-[(pyridin-3-ylmethyl)-amino]-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-[(pyridin-4-ylmethyl)-amino]-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-(cyclohexylmethyl-amino)-propionamide;

(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-carbamic acid isopropyl ester;

2-Dimethylamino-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

2-(Cyclohexylmethyl-amino)-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

2,5-Dichloro-thiophene-3-carboxylic acid (1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-phenylsulfanyl-nicotinamide;

2-(4-Chloro-phenoxy)-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-nicotinamide;

2-(4-Chloro-phenoxy)-2-methyl-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-propionamide;

N-(1-Oxo-1,2-dihydro-isoquinolin-6-yl)-succinamic acid ethyl ester;

Thiophene-2-carboxylic acid (1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

2-(4-Chloro-phenoxy)-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methyl-benzamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2,3,6-trifluoro-benzamide

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-5-fluoro-2-methyl-benzamide;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-nitro-benzamide;

2-Bromo-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2,2-dimethyl-propionamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3,3-dimethyl-butyramide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-phenylsulfanyl-nicotinamide;

2,4-Dichloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzamide;

5-Methyl-3-phenyl-isoxazole-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2,4,6-trifluoro-benzamide;

2,3-Dichloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzamide;

2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-(4-fluoro-phenyl)-propionamide;

(R)-2-Amino-2-cyclohexyl-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

(R)-Pyrrolidine-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)-Pyrrolidine-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

Piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-(4-chloro-phenyl)-propionamide;

(S)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-cyclohexyl-propionamide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-cyclohexyl-propionamide;

(R)-2-Amino-4,4-dimethyl-pentanoic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)-2-Amino-4,4-dimethyl-pentanoic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-methanesulfonyl-benzamide;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-morpholin-4-yl-benzamide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-naphthalen-2-yl-propionamide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-naphthalen-1-yl-propionamide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-pyridin-4-yl-propionamide;

2-Methyl-2-methylamino-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-propionamide;

2-Amino-2-methyl-N-(1-oxo-1,2-dihydro-isoquinolin-6-yl)-propionamide;

3-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-propionamide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-methyl-butyramide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-oxo-2-phenyl-acetamide;

(R)-Piperidine-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

2-tert-Butylamino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

(R)-2-Amino-2-cyclohexyl-N-(7-methoxy-1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

(S)-2-Amino-2-cyclohexyl-N-(7-methoxy-1-oxo-1,2-dihydro-isoquinolin-6-yl)-acetamide;

4-Bromo-2-chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzamide;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-5-methanesulfonyl-benzamide;

(R)-Tetrahydro-furan-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyano-benzamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methyl-4-nitro-benzamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-nitro-2-trifluoromethyl-benzamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-morpholin-4-ylmethyl-benzamide;

1-Amino-cyclohexanecarboxylic acid (1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(R)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyclohexylacetamide;

(R)-2-Amino-4-methyl-pentanoic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyclohexylacetamide;

(S)-2-Amino-4-methyl-pentanoic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)-2-Amino-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-methyl-butyramide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-(4-methyl-piperazin-1-ylmethyl)-benzamide;

1,2,3,4-Tetrahydro-isoquinoline-5-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1,2,3,4-Tetrahydro-isoquinoline-8-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(R)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-methyl-succinamic acid methyl ester;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-nitro-benzamide;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-5-nitro-benzamide;

(S)-Tetrahydro-furan-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-3-methylsulfanyl-propionamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyano-acetamide;

2-Bromo-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-methyl-benzamide;

Tetrahydro-pyran-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-malonamic acid ethyl ester;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methylsulfanyl-acetamide;

(S)-Pyrrolidine-3-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)-Piperidine-3-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(R)-Piperidine-3-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methanesulfonyl-acetamide;

(S)-Piperidine-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Methanesulfonyl-4-methyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

2-Chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-nitro-benzamide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-methanesulfonyl-benzamide;

(R)-Pyrrolidine-3-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-Amino-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-Amino-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-ylcarbamoyl)-cyclohexanecarboxylic acid;

(R)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-phenoxy-propionamide;

(S)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-phenoxy-propionamide;

4-Benzyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(R)-Piperidine-3-carboxylic acid (1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)-Piperidine-3-carboxylic acid (1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Methyl-piperidine-4-carboxylic acid (1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(R)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-hydroxy-3-methyl-butyramide;

piperazine-2-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-Methyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(3S,4S)-3-Methyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

Acetic acid 4-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-ylcarbamoyl)-cyclohexyl ester;

(1R,3S)-3-Amino-cyclopentanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-Hydroxy-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyclohexyl-2-hydroxy-acetamide;

(R)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyclohexyl-2-hydroxy-acetamide;

(1R,3S)-3-Amino-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(1R,3S)-3-Amino-cyclohexanecarboxylic acid (7-methoxy-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(3R,4S)-3-Methyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-Dimethylamino-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

3-Amino-cyclobutanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-4-methanesulfonyl-2-methyl-benzamide;

(3S,3S)-3-Amino-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(S)—N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-cyclohexyl-2-isopropylamino-acetamide;

(1S,2S)-2-Methyl-4-oxo-cyclohexanecarboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Isopropyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Cyclohexyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Pyridin-4-ylmethyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

N-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-2-methyl-4-(piperazine-1-sulfonyl)-benzamide;

(2S,3R)-2-Amino-3-methyl-pentanoic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Benzyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(3R,4S)-1,3-Dimethyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1,2,3,4-Tetrahydro-isoquinoline-7-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1,2,3,4-Tetrahydro-isoquinoline-6-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

4-(3-Amino-propane-1-sulfonyl)-2-chloro-N-(7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-benzamide;

(1R,5S,6R)-3-Aza-bicyclo[3.1.0]hexane-6-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

(1R,5S,6R)-3-Aza-bicyclo[3.1.0]hexane-6-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Methyl-piperidine-4-carboxylic acid (7-bromo-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Methyl-piperidine-4-carboxylic acid (7-fluoro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide;

1-Methyl-piperidine-4-carboxylic acid (7-chloro-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide; and

1-Methyl-piperidine-4-carboxylic acid (7-cyano-1-oxo-1,2-dihydro-isoquinolin-6-yl)-amide

or a tautomer or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient or carrier.