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Publication Abstract from PubMed

Two new classes of diphenylether inhibitors of p38alpha MAP kinase are described. Both chemical classes are based on a common diphenylether core that is identified by simulated fragment annealing as one of the most favored chemotypes within a prominent hydrophobic pocket of the p38alpha ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make specific interactions with either the adenine binding site or the phosphate binding site of ATP. The synthesis, crystallographic analysis, and biological activity of these p38alpha inhibitors are discussed.

Two classes of p38alpha MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes.,Michelotti EL, Moffett KK, Nguyen D, Kelly MJ, Shetty R, Chai X, Northrop K, Namboodiri V, Campbell B, Flynn GA, Fujimoto T, Hollinger FP, Bukhtiyarova M, Springman EB, Karpusas M Bioorg Med Chem Lett. 2005 Dec 1;15(23):5274-9. Epub 2005 Sep 19. PMID:16169718^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.