Benzothiazole based inhibitors of p38alpha MAP kinase
Chunjian Liu1, James Lin, Sidney Pitt
1Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. chunjian.liu@bms.com
Abstract:
Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38alpha MAP kinase are described. The issue of metabolic instability associated with vicinal phenyl, benzo[d]thiazol-6-yl oxazoles/imidazoles was addressed by the replacement of the central oxazole or imidazole ring with an aminopyrazole system. The proposed binding mode of this new class of p38alpha inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38alpha enzyme.
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