2. Academic Validation
  3. Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor

Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor

  • Bioorg Med Chem Lett. 2008 Jun 1;18(11):3200-5. doi: 10.1016/j.bmcl.2008.04.064.
Yongxin Han 1,  Michel Belley,  Christopher I Bayly,  John Colucci,  Claude Dufresne,  Andre Giroux,  Cheuk K Lau,  Yves Leblanc,  Daniel McKay,  Michel Therien,  Marie-Claire Wilson,  Kathryn Skorey,  Chi-Chung Chan,  Giovana Scapin,  Brian P Kennedy
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd, PO Box 1005, Pointe-Claire-Dorval, Que., Canada. [email protected]
PMID: 18477508 DOI: 10.1016/j.bmcl.2008.04.064
Abstract

A series of quinoline/naphthalene-difluoromethylphosphonates were prepared and were found to be potent PTP1B inhibitors. Most of these compounds bearing polar functionalities or large lipophilic residues did not show appreciable oral bioavailability in rodents while small and less polar analogs displayed moderate to good oral bioavailability. The title compound was found to have the best overall potency and pharmacokinetic profile and was found to be efficacious in animal models of diabetes and Cancer.

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