Author/Authors :
Todd A. Brugel، نويسنده , , Jennifer A. Maier، نويسنده , , Michael P. Clark، نويسنده , , Mark Sabat، نويسنده , , Adam Golebiowski، نويسنده , , Roger G. Bookland، نويسنده , , Matthew J. Laufersweiler، نويسنده , , Steven K. Laughlin، نويسنده , , John C. VanRens، نويسنده , , Biswanath De، نويسنده , , Lily C. Hsieh، نويسنده , , Marlene J. Mekel، نويسنده , , Michael J. Janusz، نويسنده ,
Abstract :
A new class of tumor necrosis factor alpha (TNF-α) synthesis inhibitors based on an N-2,4-pyrimidine-N-phenyl-N′-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar activity against lipopolysaccharide stimulated TNF-α production. X-ray co-crystallization studies with mutated p38α showed that these trisubstituted ureas interact with the ATP-binding pocket in a pseudo-bicyclic conformation brought about by the presence of an intramolecular hydrogen bonding interaction.
