Author/Authors :
Mark Sabat، نويسنده , , John C. VanRens، نويسنده , , Michael P. Clark، نويسنده , , Todd A. Brugel، نويسنده , , Jennifer Maier، نويسنده , , Roger G. Bookland، نويسنده , , Matthew J. Laufersweiler، نويسنده , , Steven K. Laughlin، نويسنده , , Adam Golebiowski، نويسنده , , Biswanath De، نويسنده , , Lily C. Hsieh، نويسنده , , Richard L. Walter and Alan M. Friedman، نويسنده , , Marlene J. Mekel، نويسنده , , Michael J. Janusz، نويسنده ,
Abstract :
A series of C-2, C-8, and N-9 trisubstituted purine based inhibitors of TNF-α production are described. The most potent analogs showed low nanomolar activity against LPS-induced TNF-α production in a THP-1 cell based assay. The SAR of the series was optimized with the aid of X-ray co-crystal structures of these inhibitors bound with mutated p38 (mp38).
Keywords :
purines , TNF-? , MAP kinase , THP-1 , Mutated p38 , THP-1 cell , p38
