2. Academic Validation
  3. Novel benzoxazole inhibitors of mPGES-1

Novel benzoxazole inhibitors of mPGES-1

  • Bioorg Med Chem Lett. 2013 Feb 1;23(3):907-11. doi: 10.1016/j.bmcl.2012.10.040.
Natasha Kablaoui 1,  Snahel Patel,  Jay Shao,  Douglas Demian,  Keith Hoffmaster,  Francioise Berlioz,  Michael L Vazquez,  William M Moore,  Richard A Nugent
Affiliations

Affiliation

  • 1 Pfizer Research Technology Center, 620 Memorial Dr., Cambridge, MA 02139, USA.
PMID: 23266122 DOI: 10.1016/j.bmcl.2012.10.040
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 μM) and PGE-2 inhibition in a cell-based assay (0.034 μM). It demonstrates 500- and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1α, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7 h half-life.

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