Benzamide analogues as parp dna repair enzyme inhibitors

C - Chemistry – Metallurgy – 07 – D

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C07D 263/56 (2006.01) A61K 31/36 (2006.01) A61K 31/423 (2006.01) A61K 31/428 (2006.01) A61K 31/517 (2006.01) A61P 35/00 (2006.01) C07D 239/88 (2006.01)

Patent

CA 2350941

A range of benzamide analogues consisting of 3- oxybenzamide derivatives are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP- ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. The compounds disclosed include certain benzoxazole-4- carboxamide compounds and in general they comprise compounds having the general structural formula I (see formula I) or pharmaceutically acceptable salt thereof, characterised in that Y and X together form a bridge -Y-X- that represents the grouping (see formula II) or (see formula III) or (see formula IV) where R5 is H, alkyl or an optionally substituted aralkyl or aryl group.

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