Synthesis and SAR optimization of quinazolin-4 (3H)-ones as poly (ADP-ribose) polymerase-1 inhibitors

SS Kulkarni, S Singh, JR Shah, WK Low…

Index: Kulkarni, Shridhar S.; Singh, Satyakam; Shah, Janki R.; Low, Woon-Kai; Talele, Tanaji T. European Journal of Medicinal Chemistry, 2012 , vol. 50, p. 264 - 273

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Citation Number: 18

Abstract

We have demonstrated that quinazolin-4 (3H)-one, a nicotinamide (NI) mimic with PARP-1 inhibitory activity in the high micromolar range (IC50= 5.75 μM) could be transformed into highly active derivatives with only marginal increase in molecular weight. Convenient one to two synthetic steps allowed us to explore extensive SAR at the 2-, and 5-through 8-positions of the quinazolin-4 (3H)-one scaffold. Substitutions at the 2-and 8-positions were found to ...