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

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

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Quebec, Canada. yves_leblanc@merck.com
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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