RHO KINASE INHIBITORS

1 . A method for treating a cardiovascular disease or condition in a warm-blooded animal which comprises administering to the animal a therapeutically effective amount of 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 OCH 2 aryl, —CH 2 OC(O)C 1-6 alkyl, —(CH 2 ) 1-3 S(O) 0-2 aryl, —(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 ) 1-2 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, heterocyclylSO 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 salt of the compound of formula (I).

2 . The method of claim 1 , wherein the cardiovascular disease or condition is selected form the group consisting of hypertension, atherosclerosis, restenosis, stroke, heart failure, coronary vasospasm, cerebral vasospasm, ischemia/reperfusion injury, pulmonary hypertension, angina, myocardial infarction, peripheral artery disease, coronary artery disease and combinations thereof.

3 . The method of 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 OCH 2 phenyl, —CH 2 OC(O)C 1-6 alkyl, —(CH 2 ) 1-3 S(O) 0-2 phenyl, —(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 and 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 salt of the compound of formula (I).

4 . The method of 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 salt of the compound of formula (I).

5 . A method of treating renal disease, erectile dysfunction, asthma, glaucoma or organ failure resulting from hypertension in a warm-blooded animal which comprises administering to the animal a therapeutically effective amount of 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 OCH 2 aryl, —CH 2 OC(O)C 1-6 alkyl, —(CH 2 ) 1-3 S(O) 0-2 aryl, —(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 ) 1-2 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, heterocyclylSO 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 salt of the compound of formula (I).

6 . The method of claim 5 , 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 OCH 2 phenyl, —CH 2 OC(O)C 1-6 alkyl, —(CH 2 ) 1-3 S(O) 0-2 phenyl, —(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 and 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 salt of the compound of formula (I).

7 . The method of claim 5 , 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 salt of the compound of formula (I).