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

…, ME Hepperle, W Naing, H Shieh, R Kurambail…

Index: Walker, John K.; Selness, Shaun R.; Devraj, Rajesh V.; Hepperle, Michael E.; Naing, Win; Shieh, Huey; Kurambail, Ravi; Yang, Syaulan; Flynn, Daniel L.; Benson, Alan G.; Messing, Dean M.; Dice, Tom; Kim, Tina; Lindmark; Monahan, Joseph B.; Portanova, Joseph Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 8 p. 2634 - 2638

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Citation Number: 15

Abstract

Starting from an initial HTS screening lead, a novel series of C (5)-substituted diaryl pyrazoles were developed that showed potent inhibition of p38α 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 ...