Identification of SD-0006, a potent diaryl pyrazole inhibitor of p38 MAP kinase

  • Bioorg Med Chem Lett. 2010 Apr 15;20(8):2634-8. doi: 10.1016/j.bmcl.2010.02.047.
John K Walker  1 ,  Shaun R Selness ,  Rajesh V Devraj ,  Michael E Hepperle ,  Win Naing ,  Huey Shieh ,  Ravi Kurambail ,  Syaulan Yang ,  Daniel L Flynn ,  Alan G Benson ,  Dean M Messing ,  Tom Dice ,  Tina Kim ,  R J Lindmark ,  Joseph B Monahan ,  Joseph Portanova
Affiliations
PMID: 20227876 DOI: 10.1016/j.bmcl.2010.02.047
Abstract

Starting from an initial HTS screening lead, a novel series of C(5)-substituted diaryl pyrazoles were developed that showed potent inhibition of p38alpha kinase. Key to this outcome was the switch from a pyridyl to pyrimidine at the C(4)-position leading to analogs that were potent in human whole blood based cell assay as well as in a number of animal efficacy models for Rheumatoid Arthritis. Ultimately, we identified a clinical candidate from this substrate; SD-0006.

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