PHTHALAZINONE DERIVATIVES AS INHIBITORS OF PARP-1

摘要

A compound of the formula (I): wherein: R represents one or more optional substituents on the fused cyclohexene ring; X can be NRX or CRXRY; if X = NRX then n is 1 or 2 and if X = CRXRY then n is 1; if X = NRX, then RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, optionally substituted C5-20 aryl, optionally substituted C3-20 heterocyclyl, optionally substituted amido, optionally substituted thioamido, optionally substituted ester, optionally substituted acyl, and optionally substituted sulfonyl groups; if X = CRXRY then Rx is selected from the group consisting of H, optionally substituted C1-20 alkyl, optionally substituted C5-20 aryl, optionally substituted C3-20 heterocyclyl, optionally substituted amido, optionally substituted thioamido, optionally substituted sulfonamino, optionally substituted ether, optionally substituted ester, optionally substituted acyl, optionally substituted acylamido, and optionally substituted sulfonyl groups and R? is selected from H, hydroxy, optionally substituted amino, or Rx and R? may together form an optionally substituted spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are both hydrogen, or when X is CRXRY, RC1, RC2, Rx and Ry, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and R1is selected from H and halo. The compounds act as inhibitors of poly(APD-ribose)synthase, PARP-1.