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Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor.
Han, Yongxin; Belley, Michel; Bayly, Christopher I; Colucci, John; Dufresne, Claude; Giroux, Andre; Lau, Cheuk K; Leblanc, Yves; McKay, Daniel; Therien, Michel; Wilson, Marie-Claire; Skorey, Kathryn; Chan, Chi-Chung; Scapin, Giovana; Kennedy, Brian P.
Afiliación
  • Han Y; Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada Ltd, PO Box 1005, Pointe-Claire-Dorval, Que., Canada. yongxin_han@merck.com
Bioorg Med Chem Lett ; 18(11): 3200-5, 2008 Jun 01.
Article en En | MEDLINE | ID: mdl-18477508
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Tirosina Fosfatasa no Receptora Tipo 1 / Organofosfonatos / Hidrocarburos Halogenados / Naftalenos Límite: Animals Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2008 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína Tirosina Fosfatasa no Receptora Tipo 1 / Organofosfonatos / Hidrocarburos Halogenados / Naftalenos Límite: Animals Idioma: En Revista: Bioorg Med Chem Lett Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2008 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido