Synthesis and biological evaluation of the 1, 5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1 H- …

TD Penning, JJ Talley, SR Bertenshaw…

Index: Penning, Thomas D.; Talley, John J.; Bertenshaw, Stephen R.; Carter, Jeffery S.; Collins, Paul W.; Docter, Stephen; Graneto, Matthew J.; Lee, Len F.; Malecha, James W.; Miyashiro, Julie M.; Rogers, Roland S.; Rogier; Yu, Stella S.; Anderson, Gary D.; Burton, Earl G.; Cogburn, J. Nita; Gregory, Susan A.; Koboldt, Carol M.; Perkins, William E.; Seibert, Karen; Veenhuizen, Amy W.; Zhang, Yan Y.; Isakson, Peter C. Journal of Medicinal Chemistry, 1997 , vol. 40, # 9 p. 1347 - 1365

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Citation Number: 1720

Abstract

A series of sulfonamide-containing 1, 5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs ...