Potent PARP inhibitors

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof, wherein

R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxycarbonyl, alkyl, alkynyl, cyano, haloalkoxy, haloalkyl, halogen, hydroxy, hydroxyalkyl, nitro, NR A R B , and (NR A R B )carbonyl;

X is heterocyclealkyl, wherein X is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents, Z, independently selected from the group consisting of alkyl, alkenyl, alkynyl, nitro, —CN, halogen, haloalkyl, alkoxy, alkylcarbonyl, alkylcarbonylalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryl, arylalkyl, arylalkoxy, arylalkoxycarbonyl, arylalkylcarbonyl, carboxy, carboxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkoxy, cycloalkylcarbonyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heteroarylcarbonylalkyl, heterocycle, heterocyclealkyl, heterocyclealkylcarbonyl, heterocyclecarbonyl, heterocyclecarbonylalkyl, hydroxy, hydroxyalkyl, NR C R D , (NR C R D )alkyl, (NR C R D )carbonyl, (NR C R D )carbonylalkyl, and oxo; wherein the aryl and the heteroaryl moieties of Z are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, formyl, halogen, and haloalkyl, and the heterocycle and cycloalkyl moieties of Z are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, oxo, formyl, halogen, and haloalkyl;

R C and R D are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, arylcarbonyl, aryl, arylalkyl, arylalkylcarbonyl, carboxyalkyl, carboxyalkylcarbonyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkylcarbonyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl, heterocyclealkylcarbonyl, (NR A R B )alkyl, and (NR A R B )alkylcarbonyl; wherein if R C or R D are aryl, arylalkyl, arylalkylcarbonyl, arylcarbonyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heteroarylcarbonyl, heterocycle, heterocyclealkyl, heterocyclecarbonyl, or heterocyclealkylcarbonyl, then R C or R D may be unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of alkyl, alkenyl, alkynyl, nitro, —CN, halogen, haloalkyl, oxo, alkoxy, alkylcarbonyl, alkylcarbonylalkyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, aryl, arylalkyl, arylalkoxy, arylalkylcarbonyl, and arylalkoxycarbonyl;

R A and R B are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, and alkylcarbonyl; and

n is 1.

2. The compound of claim 1 having Formula (II):

3. The compound of claim 2 , wherein

X is heterocyclealkyl, wherein X is unsubstituted or substituted with 1 or 2 substituents, Z, independently selected from the group consisting of alkyl, nitro, —CN, halogen, alkoxy, alkoxycarbonyl, aryl, arylalkyl, arylalkoxycarbonyl, carboxy, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, heterocyclealkylcarbonyl, NR C R D , (NR C R D )alkyl, (NR C R D )carbonyl, and oxo; wherein the aryl and the heteroaryl moieties of Z are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, formyl, halogen, and haloalkyl, and the heterocycle and cycloalkyl moieties of Z are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, oxo, formyl, halogen, and haloalkyl;

R C and R D are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, arylalkyl, arylalkylcarbonyl, arylcarbonyl, carboxyalkyl, carboxyalkylcarbonyl, cycloalkyl, haloalkyl, haloalkylcarbonyl, heteroaryl, heteroarylcarbonyl, heterocyclealkyl, heterocyclecarbonyl, heterocyclealkylcarbonyl, (NR A R B )alkyl, and (NR A R B )alkylcarbonyl; wherein if R C or R D are arylalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, heterocyclealkyl, heterocyclecarbonyl, or heterocyclealkylcarbonyl, then R C or R D may be unsubstituted or substituted with one substituent selected from the group consisting of alkoxy, alkylcarbonyl and arylalkoxycarbonyl; and

R A and R B are independently selected from the group consisting of hydrogen, alkyl, and alkylcarbonyl.

4. The compound of claim 3 , wherein R 1 , R 2 , R 3 and R 4 are hydrogen.

5. The compound of claim 1 having Formula (III):

6. The compound of claim 5 , wherein

X is heterocyclealkyl, wherein X is unsubstituted or substituted with 1 or 2 substituents, Z, independently selected from the group consisting of alkyl, nitro, —CN, halogen, alkoxy, alkoxycarbonyl, aryl, arylalkyl, arylalkoxycarbonyl, carboxy, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, heterocyclealkylcarbonyl, NR C R D , (NR C R D )alkyl, (NR C R D )carbonyl, and oxo; wherein the aryl and the heteroaryl moieties of Z are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, formyl, halogen, and haloalkyl, and the heterocycle and cycloalkyl moieties of Z are independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of alkyl, oxo, formyl, halogen, and haloalkyl;

R C and R D are independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylcarbonyloxyalkylcarbonyl, aryl, arylalkyl, arylalkylcarbonyl, arylcarbonyl, carboxyalkyl, carboxyalkylcarbonyl, cycloalkyl, haloalkyl, haloalkylcarbonyl, heteroaryl, heteroarylcarbonyl, heterocyclealkyl, heterocyclecarbonyl, heterocyclealkylcarbonyl, (NR A R B )alkyl, and (NR A R B )alkylcarbonyl; wherein if R C or R D are arylalkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, heterocyclealkyl, heterocyclecarbonyl, or heterocyclealkylcarbonyl, then R C or R D may be unsubstituted or substituted with one substituent selected from the group consisting of alkoxy, alkylcarbonyl and arylalkoxycarbonyl; and

R A and R B are independently selected from the group consisting of hydrogen, alkyl, and alkylcarbonyl.

7. The compound of claim 6 , wherein R 1 , R 2 , R 3 and R 4 are hydrogen.

8. The compound of claim 1 , selected from the group consisting of

2-piperidin-3-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-methylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-ethylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-isobutylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-cyclopropylmethylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-[1-(3-piperidin-1-ylpropionyl)piperidin-3-yl]-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-propylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-benzylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-cyclopentylmethylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-pyridin-4-ylmethylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-isopropylpiperidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-benzylpiperidin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-piperidin-4-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-methylpiperidin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-ethylpiperidin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-propylpiperidin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-cyclopropylmethylpiperidin-4-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-isobutylpiperidin-4-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-isopropylpiperidin-4-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-pyrrolidin-3-yl-4H-pyrazolo[1,5-a]quinazolin-5-one;

benzyl 3-(5-oxo-4,5-dihydropyrazolo[1,5-a]quinazolin-2-yl)pyrrolidine-1-carboxylate;

2-(1-methylpyrrolidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-ethylpyrrolidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-(1-cyclopropylmethylpyrrolidin-3-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

2-piperidin-2-yl-4H-pyrazolo[1,5-a]quinazolin-5-one; and

2-(1-methylpiperidin-2-yl)-4H-pyrazolo[1,5-a]quinazolin-5-one;

or a pharmaceutically acceptable salt thereof

9. A pharmaceutical composition comprising a compound of Formula (I) of claim 1 or a pharmaceutically acceptable salt thereof, in combination with a therapeutically acceptable carrier.