Alkoxy-substituted compounds, methods, and compositions for inhibiting PARP activity

摘要

A compound, compositions, methods of use, and processes of making formula I:or a pharmaceutically acceptable salt, hydrate, ester, solvate, prodrug, metabolite, stereoisomer, or mixtures thereof, wherein:R1, when present, is hydrogen or lower alkyl;R2 is lower alkyl, aryl, aralkyl, lower alkanoyl, or -(CH2)n-(CHOH)y(CH2)mA, wherein n is 1-4, y is 0 or 1, m is 0-5, and A is cycloalkyl, cycloalkenyl, lower alkanoyl, aryl, aralkyl, -NH2, -NH-(lower alkyl),Y represents the atoms necessary to form a fused 5- to 6-membered ring that is aromatic or nonaromatic and carbocyclic or heterocyclic;Z is(i) -CHR2CHR3- where R2 and R3 are independently hydrogen, alkyl, aryl or aralkyl;(ii) -R6C=CR3- where R6 and R3 are independently hydrogen, lower alkyl, aryl, aralkyl, chlorine, bromine or -NR7R8, where R7 and R8 are independently hydrogen or lower alkyl, or, R6 and R3, taken together, form a fused 5- to 6-membered ring that is aromatic or nonaromatic and carbocyclic or heterocyclic;(iii) -R2C=N-;(iv) -CR2(OH)-NR7-; or(v) -C(O)-NR7-.