Discovery of PH-797804, a highly selective and potent inhibitor of p38 MAP kinase

  • Bioorg Med Chem Lett. 2011 Jul 1;21(13):4066-71. doi: 10.1016/j.bmcl.2011.04.121.
Shaun R Selness  1 ,  Rajesh V Devraj ,  Balekudru Devadas ,  John K Walker ,  Terri L Boehm ,  Richard C Durley ,  Huey Shieh ,  Li Xing ,  Paul V Rucker ,  Kevin D Jerome ,  Alan G Benson ,  Laura D Marrufo ,  Heather M Madsen ,  Jeff Hitchcock ,  Tom J Owen ,  Lance Christie ,  Michele A Promo ,  Brian S Hickory ,  Edgardo Alvira ,  Win Naing ,  Radhika Blevis-Bal ,  Dean Messing ,  Jerry Yang ,  Michael K Mao ,  Gopi Yalamanchili ,  Richard Vonder Embse ,  Jeffrey Hirsch ,  Matthew Saabye ,  Sheri Bonar ,  Elizabeth Webb ,  Gary Anderson ,  Joseph B Monahan
Affiliations
  • 1. Department of Medicinal Chemistry, Pfizer Corporation, 700 Chesterfield Parkway West, Chesterfield, MO 63017, United States. [email protected]
PMID: 21641211 DOI: 10.1016/j.bmcl.2011.04.121
Abstract

The synthesis and SAR studies of a novel N-aryl pyridinone class of p38 kinase inhibitors are described. Systematic structural modifications to the HTS lead, 5, led to the identification of (-)-4a as a clinical candidate for the treatment of inflammatory diseases. Additionally, the chiral synthesis and properties of (-)-4a are described.

Products