1. 4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2).
- Author
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Talley JJ, Bertenshaw SR, Brown DL, Carter JS, Graneto MJ, Koboldt CM, Masferrer JL, Norman BH, Rogier DJ Jr, Zwwifel BS, and Seibert K
- Subjects
- Animals, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Humans, Membrane Proteins, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cyclooxygenase Inhibitors pharmacology, Isoenzymes drug effects, Oxazoles pharmacology, Prostaglandin-Endoperoxide Synthases drug effects
- Abstract
A series of methysulfonyl or sulfonamido substituted 4,5-diaryloxazole were prepared and evaluated for their ability to inhibit the inducible form of cyclooxygenase (COX-2) in vitro and in vivo. Several unique substitution patterns were identified that led to potent and selective inhibitors of COX-2. In general, 2-trifluoromethly-4,5-diaryloxazoles substituted with a methylsulfonyl or sulfonamido group were particularly potent inhibitors. One of the more potent compounds with a selectivity for COX-2 of about 800 fold was 4b (SC-299). SC-299, a highly fluorescent molecule, may be useful for spectroscopic studies on preferential inhibitor binding to COX-2.
- Published
- 1999
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