Discovery and SAR of substituted 3-oxoisoindoline-4-carboxamides as potent inhibitors of poly(ADP-ribose) polymerase (PARP) for the treatment of cancer
Graphical abstract
We have discovered a series of compounds with a 3-oxoisoindoline-4-carboxamide core structure as potent PARP inhibitors. The highlight of the core is a conformational restriction of a benzamide by formation of a seven-membered hydrogen-bond with an oxindole carbonyl group, with compound 1e identified as the most potent in vitro PARP-1 inhibitor.
Section snippets
Acknowledgment
The authors are grateful to the Abbott analytical department for acquisition of 1H NMR and MS.
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