Substrate-selective inhibition of cyclooxygenase-2: development and evaluation of achiral profen probes

MA Windsor, DJ Hermanson, PJ Kingsley…

Index: Windsor, Matthew A.; Hermanson, Daniel J.; Kingsley, Philip J.; Xu, Shu; Crews, Brenda C.; Ho, Winnie; Keenan, Catherine M.; Banerjee, Surajit; Sharkey, Keith A.; Marnett, Lawrence J. ACS Medicinal Chemistry Letters, 2012 , vol. 3, # 9 p. 759 - 763

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Citation Number: 19

Abstract

Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2- arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The ...