Synthesis and structure–activity relationships of novel poly (ADP-ribose) polymerase-1 inhibitors

M Tao, CH Park, R Bihovsky, GJ Wells, J Husten…

Index: Tao, Ming; Park, Chung Ho; Bihovsky, Ron; Wells, Gregory J.; Husten, Jean; Ator, Mark A.; Hudkins, Robert L. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 4 p. 938 - 942

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Citation Number: 45

Abstract

A series of novel pyrrolocarbazoles was synthesized as potential PARP-1 inhibitors. Pyrrolocarbazole 1 was identified as a potent PARP-1 inhibitor (IC50= 36nM) from our internal database. Synthesis of analogs around this template with the aid of modeling studies led to the identification of the truncated imide 14. Compound 14 (IC50= 40nM), with deleted B-ring, was found to be an equipotent PARP-1 inhibitor.

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