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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Han, Y; Belley, M; Bayly, CI; Colucci, J; Dufresne, C; Giroux, A; Lau, CK; Leblanc, Y; McKay, D; Therien, M; Wilson, M-C; Skorey, K; Chan, C-C; Scapin, G; Kennedy, BP

Published Date

  • June 2008

Published In

Volume / Issue

  • 18 / 11

Start / End Page

  • 3200 - 3205

PubMed ID

  • 18477508

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2008.04.064


  • eng