Synthesis and Evaluation of 3-Aroylindoles as Anticancer Agents: Metabolite Approach
- 8 July 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 52 (15) , 4941-4945
Abstract
BPR0L075 (2) is a potential anticancer drug candidate designed from Combretastatin A-4 (1) based on the bioisosterism principle. Metabolites of 2, proposed from in vitro human microsome studies, were synthesized, leading to the identification of metabolite-derived analogue 10 with 40−350 pM potency against various cancer cell lines. Insights gained from the major inactive metabolite of 2 led to the development of 29, with better pharmacokinetics and improved potency in the tumor xenograft model than 2.Keywords
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