Novel benzoxazole inhibitors of mPGES-1.

Novel benzoxazole inhibitors of mPGES-1.

Bioorg Med Chem Lett. 2012 Oct 16;

Authors: Kablaoui N, Patel S, Shao J, Demian D, Hoffmaster K, Berlioz F, Vazquez ML, Moore WM, Nugent RA

Abstract
A novel series of potent benzoxazole mPGES-1 inhibitors has been derived from a hit from a high throughput screen. Compound 37 displays mPGES-1 inhibition in an enzyme assay (0.018?M) and PGE-2 inhibition in a cell-based assay (0.034?M). It demonstrates 500- and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1?, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7h half-life.

PMID: 23266122 [PubMed - as supplied by publisher]

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