Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development

  • Bioorg Med Chem Lett. 2006 Aug 15;16(16):4339-44. doi: 10.1016/j.bmcl.2006.05.056.
Kim F McClure  1 ,  Michael A Letavic ,  Amit S Kalgutkar ,  Christopher A Gabel ,  Laurent Audoly ,  John T Barberia ,  John F Braganza ,  Demetrius Carter ,  Thomas J Carty ,  Santo R Cortina ,  Mark A Dombroski ,  Kathleen M Donahue ,  Nancy C Elliott ,  Colleen P Gibbons ,  Crystal K Jordan ,  Alexander V Kuperman ,  Jeff M Labasi ,  Ronald E Laliberte ,  Jennifer M McCoy ,  Brian M Naiman ,  Kendra L Nelson ,  Hang T Nguyen ,  Kevin M Peese ,  Francis J Sweeney ,  Timothy J Taylor ,  Catherine E Trebino ,  Yuriy A Abramov ,  Ellen R Laird ,  Walter A Volberg ,  Jun Zhou ,  Justin Bach ,  Franco Lombardo
Affiliations
  • 1. Pfizer Global Research and Development, Groton Laboratories, CT 06340, USA. [email protected]
Abstract

The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates.