Substituted AZA-indoles as inhibitors of poly(ADP-ribose) polymerase (PARP)

A compound, enantiomers, stereoisomers, and tautomers of said compound and pharmaceutically acceptable salts thereof, with said compound having the general structure shown in formula (I):

• wherein
• R is hydrogen, hydroxy, C1-4alkoxy or amino;
• R1 is naphthyl, substituted phenyl, C6-12arylC1-4alkyl, C6-12arylsulfonyl or heteroaryl, and
• wherein said naphthyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from the group consisting of halogen, C1-6alkyl, C1-6alkenyl, fluoroalkyl or fluoroalkoxy of the formula CnHxFy or OCnHxFy wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, C1-4alkoxy, C1-4thioalkyl, hydroxy, hydroxyC1-4alkyl, C1-4acyloxy, nitro, amino, C1-4alkylamino, C1-4dialkylamino, aminoC1-4alkyl, C1-4alkylaminoC1-4alkyl, C1-4dialkylaminoC1-4alkyl, —CN, —CO2H, —CO2C1-4alkyl, —NHCOC1-4alkyl, substituted or unsubstituted phenyl, substituted or unsubstituted phenoxy, substituted or unsubstituted benzyloxy, substituted or unsubstituted pyrrolyl and substituted or unsubstituted pyridyl;
• R2 and R3 are the same or different and are each independently selected from:
• hydrogen, C1-4alkyl, C1-4dialkylaminoC1-4alkyl, pyrrolidinylC1-4alkyl, imidazolyl or heterocycle selected from morpholinyl, thiomorpholinyl, aziridinyl, pyrrolidinyl, piperidinyl, azepanyl, piperazinyl, diazepanyl, diazabicyclo[2.2.1]hept-2-yl and triazocanyl;
• and wherein said heterocycle is optionally substituted with one or more substituents selected from the group consisting of C1-4alkyl, oxo, —CHO and —CO2C1-4alkyl;
• or
• R2 and R3 taken together with the nitrogen atom to which they are attached form an imidazolyl or a heterocycle selected from morpholinyl, thiomorpholinyl, aziridinyl, pyrrolidinyl, piperidinyl, azepanyl, piperazinyl, diazepanyl, diazabicyclo[2.2.1]hept-2-yl and triazocanyl;
• and wherein said heterocycle is optionally substituted with one or more substituents selected from the group consisting of C1-4alkyl, oxo, —CHO, —CO2C1-4alkyl, hydroxyC1-4alkyl, oxiranylC1-4alkyl, dihydroxyC1-4alkyl, —(CH2)aN—CO2C1-4alkyl, hydroxyl, and —(CH2)aOPO(OC1-4alkyl)2, wherein a is an integer from 1 to 4;
• R4 is C1-4alkyl, fluoroalkyl or fluoroalkoxy of the formula CnHxFy or OCnHxFy wherein n is an integer from 1 to 4, x is an integer from 0 to 8, y is an integer from 1 to 9 and sum of x and y is 2n+1, C1-4alkoxy or C1-4thioalkyl;
• and
• X is nitrogen and Y is CH or X is CH and Y is nitrogen.