Document Report Card

ID: ALA1149171

Journal: J Med Chem

Title: Development of orally bioavailable bicyclic pyrazolones as inhibitors of tumor necrosis factor-alpha production.

Authors: Clark MP, Laughlin SK, Laufersweiler MJ, Bookland RG, Brugel TA, Golebiowski A, Sabat MP, Townes JA, VanRens JC, Djung JF, Natchus MG, De B, Hsieh LC, Xu SC, Walter RL, Mekel MJ, Heitmeyer SA, Brown KK, Juergens K, Taiwo YO, Janusz MJ.

Abstract: 2-Aryl-3-pyrimidinyl based tumor necrosis factor-alpha (TNF-alpha) inhibitors, which contain a novel bicyclic pyrazolone core, are described. Many showed low-nanomolar activity against lipopolysaccharide-induced TNF-alpha production in monocytic cells. Secondary screening data are presented for the pyrimidinyl bicyclic pyrazolones. Several of these analogues showed good oral bioavailability in rat and efficacy in the rat iodoacetate in vivo model.

CiteXplore: 15139749

DOI: 10.1021/jm049968m