Isoquinoline derivatives

1. An isoquinoline having the Formula I

wherein

X is O, S or NH;

Y is OH or NH 2 ;

m is 0, 1 or 2;

n is 1 or 2;

R 1 is H, when Y is NH 2 ; or R 1 is H, (C 1-4 )alkyl or halogen, when Y is OH;

R 2 and R 3 are independently H, (C 1-4 )alkyl or halogen;

R is H or (C 1-6 )alkyl, optionally substituted with OH, (C 1-4 )alkyloxy, (C 1-4 )-alkyloxycarbonyl, (C 3-7 )cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C 6-10 )aryl, (C 6-10 )aryloxy or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, (C 1-4 )alkylsulfonyl and halogen; or a pharmaceutically acceptable salt thereof.

2. The isoquinoline of claim 1 , wherein

X is O, S or NH;

Y is OH or NH 2 ;

R 1 and R 2 are H;

R 3 is H or (C 1-4 )alkyl;

m is 0 or 1;

n is 1 or 2;

R is H or (C 1-4 )alkyl, optionally substituted with (C 3-7 )cycloalkyl, which may optionally comprise a heteroatom selected from O and S, (C 6-10 )aryl or a 5- or 6-membered heteroaryl group comprising 1-3 heteroatoms independently selected from O, N and S, each aryl or heteroaryl group being optionally substituted with 1-3 substituents independently selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy and halogen; or a pharmaceutically acceptable salt thereof.

3. The isoquinoline of claim 1 , wherein Y is OH.

4. The isoquinoline of claim 1 , wherein X is O.

5. The isoquinoline of claim 1 , wherein R 3 is independently H, methyl or halogen, R 1 and R 2 are H, and R is H, (C 1-4 )alkyl, optionally substituted with phenyl or a 5- or 6-membered (C 2-5 )heteroaryl group comprising 1-3 heteroatoms selected from O, N and S, the phenyl or heteroaryl group being optionally substituted with 1-3 substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy and one or more halogens.

6. The isoquinoline of claim 1 , wherein Y is OH, m is 1, n is 1 or 2, and R is H.

7. The isoquinoline which is selected from

(S)-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one;

(S)-7-methyl-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one;

6-(perhydroazepin-4-yloxy)-2H-isoquinolin-1-one;

(S)-6-[1-(1H-pyrrol-2-ylmethyl)-piperidin-3-yloxy]-isoquinolin-1-ylamine;

(S)-6-[1-(4-methylbenzyl)piperidin-3-yloxy]isoquinolin-1-ylamine;

6-(piperidin-4-yloxy)-2H-isoquinolin-1-one;

(R)-6-(1-benzylpiperidin-3-yloxy)isoquinolin-1-ylamine;

6-[1-(2-phenoxyethyl)piperidin-3-yloxy]isoquinolin-1-ylamine;

(3S)-6-[1-(1-phenylethyl)piperidin-3-yloxy]isoquinolin-1-ylamine;

6-(piperidin-4-ylsulfanyl)-2H-isoquinolin-1-one;

6-(1-thiophen-2-ylmethylpiperidin-3-yloxy)isoquinolin-1-ylamine;

(S)-6-(1-benzylpiperidin-3-yloxy)isoquinolin-1-ylamine;

(R) 6-[1-(2-phenoxyethyl)-piperidin-3-yloxy]-2H-isoquinolin-1-one;

(S)-6-[1-(4-fluorobenzyl)-piperidin-3-yloxy]-isoquinolin-1-ylamine;

(S)-4-bromo-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one;

6-[1-(1H-pyrrol-2-ylmethyl)piperidin-4-yloxy]-2H-isoquinolin-1-one;

6-[1-(4-methoxybenzyl)piperidin-3-yloxy]-2H-isoquinolin-1-one;

(S)-6-[1-furan-3-ylmethylpiperidin-3-yloxy]isoquinolin-1-ylamine;

6-[1-phenethylpiperidin-3-yloxy]isoquinolin-1-ylamine;

6-[1-(3-methoxybenzyl)piperidin-4-yloxy]-2H-isoquinolin-1-one;

(S)-6-[1-(1H-pyrrol-3-ylmethyl)piperidin-3-yloxy]isoquinolin-1-ylamine;

(S)-6-[1-(2-oxo-2-phenylethyl)piperidin-3-yloxy]-2H-isoquinolin-1-one;

(S)-6-(pyrrolidin-3-yloxy)-2H-isoquinolin-1-one;

6-(1-cyclohexylmethylpiperidin-3-yloxy)-2H-isoquinolin-1-one;

6-(piperidin-3-ylsulfanyl)isoquinolin-1-ylamine;

6-(1-furan-2-ylmethylpiperidin-4-yloxy)-2H-isoquinolin-1-one.;

(R)-6-( pyrrolidin-3-ylsulfanyl)isoquinolin-1-ylamine;

(S)4-methyl-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one;

(S)-6-( pyrrolidin-3-ylsulfanyl)isoquinolin-1-ylamine;

6-(1-methylpiperidin-4-yloxy)-2H-isoquinolin-1-one;

(S)-6-(piperidin-3-yloxy)-isoquinolin-1-ylamine;

6-(piperidin-4-ylsulfanyl)isoquinolin-1-ylamine;

(R)-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one;

(S)-6-[1-(2-phenoxyethyl)piperidin-3-yloxy]-2H-isoquinolin-1-one;

6-(1-benzylpiperidin-3-yloxy)-7-methylisoquinolin-1-ylamine;

6-[1-(3-hydroxypropyl)piperidin-4-yloxy]-2H-isoquinolin-1-one;

6-[1-(2-hydroxyethyl)piperidin-4-yloxy]-2H-isoquinolin-1-one;

(R)-6-(pyrrolidin-3-yloxy)-2H-isoquinolin-1-one;

6-[1-(3-methylbenzyl)piperidin-4-yloxy]-2H-isoquinolin-1-one;

7-methyl-6-[1-(4-methylbenzyl)piperidin-3-yloxy]isoquinolin-1-ylamine;

(S)-5-bromo-6-(piperidin-3-yloxy)-2H-isoquinolin-1-one;

6-[1-(4-methoxybenzyl)piperidin-4-yloxy]-2H-isoquinolin-1-one, or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising an isoquinoline of claim 1 , or a pharmaceutically acceptable salt thereof, in admixture with pharmaceutically acceptable auxilliaries.

9. A method for treating ROCK-I related disorders in a patient, the method comprising administering to the patient an effective amount of the isoquinoline according to claim 1 .

10. The method of claim 9 , wherein the ROCK-I related disorders are selected from the group consisting of hypertension, atherosclerosis and glaucoma.