| 摘要 |
Compounds of the formula (I):;
wherein A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X═NRX then n is 1 or 2 and if X═CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a 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
R1 is selected from H and halo. |
| 主权项 |
1. A method of treatment for prostate or pancreatic cancer deficient in a HR dependent DNA DSB repair pathway comprising administering to a subject a therapeutically effective amount of a compound of formula (Ib): or an isomer or salt thereof, or a mixture of any thereof, wherein: A and B together represent a fused aromatic ring, optionally substituted with one or more substituent groups selected from halo, nitro, hydroxyl, ether, thiol, thioether, amino, C1-7 alkyl, C5-1 aryl and a heterocyclyl group having from 3 to 7 ring atoms, of which from 1 to 4 are selected from nitrogen, oxygen and sulfur; RX is selected from H, C1-7 alkyl, C5-7 aryl, amido, thioamido, ester, acyl, sulfonyl groups and a heterocyclyl group having from 3 to 7 ring atoms, of which from 1 to 4 are selected from nitrogen, oxygen and sulfur, wherein the acyl, C1-7 alkyl, C5-7 aryl or heterocyclyl group is optionally substituted with one or more substituent groups selected from C1-7 alkyl, C5-7 aryl, halo, hydroxyl, ether, nitro, cyano, acyl, carboxy, ester, amido, amino, acylamido, ureido, acyloxy, thiol, thioether, sulfoxide, sulfonyl, thioamido, sulfonamido and a heterocyclyl group having from 3 to 7 ring atoms, of which from 1 to 4 are selected from nitrogen, oxygen and sulfur; RC1 and RC2 are both hydrogen; and R1 is selected from H and halo; wherein the cancer is prostate or pancreatic cancer; and wherein the cancer comprises one or more cancer cells having a reduced or abrogated ability to repair DNA DSB by HR relative to normal cells. |
