Author/Authors :
Jennifer A. Townes، نويسنده , , Adam Golebiowski، نويسنده , , Michael P. Clark، نويسنده , , Matthew J. Laufersweiler، نويسنده , , Todd A. Brugel، نويسنده , , Mark Sabat، نويسنده , , Roger G. Bookland، نويسنده , , Steve K. Laughlin، نويسنده , , John C. VanRens، نويسنده , , Biswanath De، نويسنده , , Lily C. Hsieh، نويسنده , , Susan C. Xu، نويسنده , , Michael J. Janusz، نويسنده , , Richard L. Walter and Alan M. Friedman، نويسنده ,
Abstract :
4-Aryl-5-pyrimidyl-based cytokine synthesis inhibitors of TNF-α production, which contain a novel bicyclic pyrazole heterocyclic core, are described. Many of these inhibitors showed low nanomolar activity against LPS-induced TNF-α production in a THP-1 cell-based assay and against human p38α MAP kinase in an isolated enzyme assay. The X-ray crystal structure of a bicyclic pyrazole inhibitor co-crystallized with mutated p38 (mp38) is presented.
Keywords :
Bicyclic pyrazole , TNF-a , p38 , Anti-inflammatory.* Corresponding author. Tel.: +1-5136224539 , e-mail: townes.ja@pg.com , fax: +1-5136223681
