Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 15, Pages 4050-4054Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.06.016
Keywords
PARP-1; Poly(ADP-ribose)polymerase; Quinoxalinone; Nuclear enzyme; DNA repair; Programmed cell death; Nicotinamide
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Based on screening hit 1, a series of tricyclic quinoxalinones have been designed and evaluated for inhibition of PARP-1. Substitutions at the 7- and 8-positions of the quinoxalinone ring led to a number of compounds with good enzymatic and cellular potency. The tricyclic quinoxalinone class is sensitive to modifications of both the amine substituent and the tricyclic core. The synthesis and structure-activity relationship studies are presented. (C) 2009 Elsevier Ltd. All rights reserved.
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