Author/Authors :
Donald J. P. Pinto، نويسنده , , Robert A. Copeland، نويسنده , , Maryanne B. Covington، نويسنده , , William J. Pitts، نويسنده , , Douglas G. Batt، نويسنده , , Michael J. Orwat، نويسنده , , Gilbert N. Lam، نويسنده , , Amita Joshi، نويسنده , , Yuk-Charn Chan، نويسنده , , Shuaige Wang، نويسنده , , James M. Trzaskos، نويسنده , , Ronald L. Magolda، نويسنده , , David M. Kornhauser، نويسنده ,
Abstract :
DuP697, 2-bromo-4-(4′-sulfonylmethyl)phenyl-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.
