| 18477508 |
Han Y, Belley M, Bayly CI, Colucci J, Dufresne C, Giroux A, Lau CK, Leblanc Y, McKay D, Therien M, Wilson MC, Skorey K, Chan CC, Scapin G, Kennedy BP: 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. Epub 2008 Apr 29.
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. |
32(0,1,1,2) |