Two classes of p38α MAP kinase inhibitors having a common diphenylether core but exhibiting divergent binding modes

…, X Chai, K Northrop, V Namboodiri, B Campbell…

Index: Michelotti, Enrique L.; Moffett, Kristofer K.; Nguyen, Duyan; Kelly, Martha J.; Shetty, Rupa; Chai, Xiaomei; Northrop, Katrina; Namboodiri, Variketta; Campbell, Brandon; Flynn, Gary A.; Fujimoto, Ted; Hollinger, Frank P.; Bukhtiyarova, Marina; Springman, Eric B.; Karpusas, Michael Bioorganic and Medicinal Chemistry Letters, 2005 , vol. 15, # 23 p. 5274 - 5279

Full Text: HTML

Citation Number: 23

Abstract

Two new classes of diphenylether inhibitors of p38α 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 p38α ATP-binding site. In the fully elaborated molecules, the diphenylether moiety acts as an anchor occupying the deep pocket, while polar extensions make ...