Thiazolyl-and oxazolyl-isoquinolinones and methods for using them

1. A compound of Formula I:

wherein:

X is C 1 -C 9 alkylene, C 2 -C 9 alkenylene, or C 2 -C 9 alkynylene;

Y is O or S;

R 1 is hydrogen, hydroxy, or OR 7 ;

R 2 , R 3 , and R 4 are independently hydrogen;

R 5 and R 6 are each, independently, C 1 C 6 alkyl, wherein the alkyl is optionally substituted with one or more groups selected from hydroxy, C 1 -C 4 alkoxy, —CO 2 H, C 1 -C 6 alkoxycarbonyl, NH 2 , C 1 -C 6 mono- or dialkylamino, and halogen; or

R 5 and R 6 together with the nitrogen to which they are attached form a saturated, partially unsaturated, or unsaturated 3 to 12 membered monocyclic or bicyclic heterocyclic ring optionally comprising from one to three additional ring heteroatoms selected from N, O, and S, and the remainder of the ring atoms are carbon atoms;

R 7 is C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 3 -C 7 cycloalkyl wherein the alkyl, alkenyl, and rings of the cycloalkyl are optionally substituted with one or more groups selected from hydroxy, C 1 -C 4 alkoxy, —CO 2 H, C 1 -C 6 alkoxycarbonyl, NH 2 , C 1 -C 6 mono- or dialkylamino, and halogen;

or a pharmaceutically acceptable salt form thereof.

2. The compound of claim 1 wherein R 1 is hydrogen or hydroxy or a pharmaceutically acceptable salt form thereof.

3. The compound of claim 1 having Formula III:

or a pharmaceutically acceptable salt form thereof.

4. The compound of claim 1 wherein X is C 1 -C 3 alkylene, C 2 -C 3 alkenylene, or C 2 -C 3 alkynylene.

5. The compound of claim 1 wherein Y is O.

6. The compound of claim 1 wherein Y is S.

7. The compound of claim 1 wherein R 5 and R 6 are each, independently, C 1 -C 6 alkyl.

8. The compound of claim 1 wherein R 5 and R 6 together with the nitrogen to which they are attached form a saturated monocyclic heterocyclic ring optionally comprising from one to three additional ring heteroatoms selected from N, O, and S, and the remainder of the ring atoms are carbon atoms.

9. The compound of claim 8 wherein R 5 and R 6 together with the nitrogen to which they are attached form piperidine, morpholine, pyrrolidine, homopiperidine, aziridine, or azetidine.

10. The compound of claim 1 wherein X is C 1 -C 3 alkynylene.

11. The compound of claim 1 wherein:

Y is S;

X is C 1 -C 3 alkylene; and

R 5 and R 6 are each, independently, C 1 -C 6 alkyl.

12. The compound of claim 1 wherein:

Y is O;

X is C 1 -C 3 alkylene; and

R 5 and R 6 are each, independently, C 1 -C 6 alkyl.

13. The compound of claim 1 that is:

2-[(Dimethylamino)methyl[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

2-[3-(Dimethylamino)prop-1-yn-1-yl][1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

2-(2-(Dimethylamino)ethyl)thiazolo[5,4-c]isoquinolin-5(4H)-one;

2-((Dimethylamino)methyl)-9-hydroxythiazolo[5,4-c]isoquinolin-5(4H)-one;

9-Hydroxy-2-(morpholin-4-ylmethyl)[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

9-Hydroxy-2-(piperidin-1-ylmethyl)[1,3]thiazolo[5,4-disoquinolin-5(4H)-one;

9-Hydroxy-2-(pyrrolidin-1-ylmethyl)[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

2-{[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-9-hydroxy[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

9-Hydroxy-2-(octahydroquinolin-1(2H)-ylmethyl)[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

2-{[(2R,6S)-2,6-Dimethylmorpholin-4-yl]methyl}-9-hydroxy[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

9-Hydroxy-2-[(2-methylpyrrolidin-1-yl)methyl][1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

9-Hydroxy-2-{[(2R)-2-(trifluoromethyl)pyrrolidin-1-yl]methyl}[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

2-{[(2R,6S)-2,6-Dimethylpiperidin-1-yl]methyl}-9-hydroxy[1,3]thiazolo[5,4-c]isoquinolin-5(4H)-one;

and a pharmaceutically acceptable salt form thereof.

14. A pharmaceutical composition comprising a pharmaceutically acceptable effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

15. A method for inhibiting poly(ADP-ribose) polymerase in a subject comprising administering to the subject an effective amount of a compound of claim 1 to inhibit poly(ADP-ribose) polymerase in the subject.

16. The compound of claim 1 , wherein R 1 is hydrogen.