Author/Authors :
Chunjian Liu، نويسنده , , Ming-Ji James Lin، نويسنده , , Sidney Pitt، نويسنده , , Rosemary F. Zhang، نويسنده , , John S. Sack، نويسنده , , Susan E. Kiefer، نويسنده , , Kevin Kish، نويسنده , , Arthur M. Doweyko، نويسنده , , Hongjian Zhang، نويسنده , , Punit H. Marathe، نويسنده , , James Trzaskos، نويسنده , , Murray McKinnon، نويسنده , , John H. Dodd، نويسنده , , Joel C. Barrish، نويسنده , , Gary L. Schieven، نويسنده , , Katerina Leftheris، نويسنده ,
Abstract :
Rational design, synthesis, and SAR studies of a novel class of benzothiazole based inhibitors of p38α 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 p38α inhibitors was confirmed by X-ray crystallographic studies of a representative inhibitor (6a) bound to the p38α enzyme.
Keywords :
Inhibitors of p38? MAP kinase , Vicinal phenyl , Vicinal phenyl , Vicinal phenyl , X-ray co-crystal structure , Benzothiazoles , TNF? inhibition in hPBMC
