4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2)

✍ Scribed by John J. Talley; Stephen R. Bertenshaw; David L. Brown; Jeffery S. Carter; Mathew J. Graneto; Carol M. Koboldt; Jaime L. Masferrer; Bryan H. Norman; D. Joseph Rogier Jr.; Ben S. Zweifel; Karen Seibert

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 96 KB
• Volume: 19
• Category: Article
• ISSN: 0198-6325
• DOI: 10.1002/(sici)1098-1128(199905)19:3<199::aid-med1>3.0.co;2-7

✦ Synopsis

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.