Chemistry and pharmacokinetics of diarylthiophenes and terphenyls as selective COX-2 inhibitors

✍ Scribed by Donald J.P. Pinto; Robert A. Copeland; Maryanne B. Covington; William J. Pitts; Douglas G. Batt; Michael J. Orwat; Gilbert N. Lam; Amita Joshi; Yuk-Charn Chan; Shuaige Wang; James M. Trzaskos; Ronald L. Magolda; David M. Kornhauser

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 330 KB
• Volume: 6
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/s0960-894x(96)00513-6

✦ Synopsis

DuP697, 2-bromo-4-(4'-sulfonylmethyl)phenyt-5-(4'-fluoro)phenylthiophene, is a selective type 2 cyclooxygenase (COX-2) inhibitor. Its relatively weak COX-2 selectivity coupled with a poor human pharmacokinetic profile led us to seek improvements on the in vitro selectivity while at the same time, addressing some of its pharmacokinetic liabilities. In this paper we discuss some strategies at solving the PK issue within a class of COX-2 inhibitors. The result of these efforts led to the discovery of a new class of COX-2 inhibitors the terphenyls, which prove to be superior alternatives to the diarylthiophenes.