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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Identification of SD-0006, a potent diaryl pyrazole inhibitor of p38 MAP kinase
John K Walker1, Shaun R Selness, Rajesh V Devraj
1Pfizer Global Research and Development, St. Louis, MO 63017, USA. jkwalker24@sbcglobal.net
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.
