The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase inhibitors

  • Bioorg Med Chem Lett. 2008 Mar 15;18(6):1772-7. doi: 10.1016/j.bmcl.2008.02.033.
Antonio Garrido Montalban  1 ,  Erik Boman ,  Chau-Dung Chang ,  Susana Conde Ceide ,  Russell Dahl ,  David Dalesandro ,  Nancy G J Delaet ,  Eric Erb ,  Justin T Ernst ,  Andrew Gibbs ,  Jeffrey Kahl ,  Linda Kessler ,  Jan Lundström ,  Stephen Miller ,  Hiroshi Nakanishi ,  Edward Roberts ,  Eddine Saiah ,  Robert Sullivan ,  Zhijun Wang ,  Christopher J Larson
Affiliations
  • 1. Drug Discovery, Kémia, Inc., 5871 Oberlin Drive, Suite 100, San Diego, CA 92121, USA. [email protected]
PMID: 18325768 DOI: 10.1016/j.bmcl.2008.02.033
Abstract

We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.