The 2′-trifluoromethyl analogue of indomethacin is a potent and selective COX-2 inhibitor

…, BC Crews, CA Rouzer, LJ Marnett

Index: Blobaum, Anna L.; Uddin, Md. Jashim; Felts, Andrew S.; Crews, Brenda C.; Rouzer, Carol A.; Marnett, Lawrence J. ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 5 p. 486 - 490

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Citation Number: 24

Abstract

Indomethacin is a potent, time-dependent, nonselective inhibitor of the cyclooxygenase enzymes (COX-1 and COX-2). Deletion of the 2′-methyl group of indomethacin produces a weak, reversible COX inhibitor, leading us to explore functionality at that position. Here, we report that substitution of the 2′-methyl group of indomethacin with trifluoromethyl produces CF3–indomethacin, a tight-binding inhibitor with kinetic properties similar to those of ...