AMINO-SUBSTITUTED COMPOUNDS, METHODS, AND COMPOSITIONS FOR INHIBITING PARP ACTIVITY

摘要

A compound of 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; X is -NR4R5, where R?4 and R5¿ are independently hydrogen, lower alkyl, aralkyl, aryl, lower alkanoyl or -(CH¿2?)n(CHOH)y(CH2)m-NR?9R10¿, where n is 1-4, y is 0 or 1, m is 0-5, and R?9 and R10¿ are independently hydrogen, lower alkyl, aralkyl, aryl, or lower alkanoyl; 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 R?2 and R3¿ are independently hydrogen, alkyl, aryl, or aralkyl; (ii) -R6C=CR3- where R?6 and R3¿ are independently hydrogen, lower alkyl, aryl, aralkyl, chlorine, bromine or -NR7R8, where R?7 and R8¿ are independently hydrogen or lower alkyl, or, R?6 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) -CR?2(OH)-NR7¿-; or (v) -C(O)-NR7-; pharmaceutical compositions containing the same, methods of using the same, and processes for making the same.