Discovery of a potent and selective COX-2 inhibitor in the alkoxy lactone series with optimized metabolic profile

  • Bioorg Med Chem Lett. 2002 Nov 18;12(22):3317-20. doi: 10.1016/s0960-894x(02)00739-4.
Yves Leblanc  1 ,  Patrick Roy ,  Zhaoyin Wang ,  Chun Sing Li ,  Nathalie Chauret ,  Deborah A Nicoll-Griffith ,  José M Silva ,  Yves Aubin ,  James A Yergey ,  Chi Chung Chan ,  Denis Riendeau ,  Christine Brideau ,  Robert Gordon ,  Lijing Xu ,  Janine Webb ,  Denise M Visco ,  Petpiboon Prasit
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Quebec, Canada. [email protected]
PMID: 12392741 DOI: 10.1016/s0960-894x(02)00739-4
Abstract

The COX-2 Inhibitor DFP [5,5-dimethyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone] was found to have a long half-life in humans. Analogues have been characterized in order to optimize pharmacokinetics. This has lead to the discovery of 5(S)-(5-ethyl-5-methyl-3-(2-propoxy)-4-methanesulfonylphenyl)-2(5H)-furanone analogue 11 a potent and selective COX-2 Inhibitor which is metabolized to a greater extent than DFP upon incubation with rat and human hepatocytes, suggesting a shorter half-life in humans.

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