Benzenesulfonamide indole inhibitors of cytosolic phospholipase A2α: Optimization of in vitro potency and rat pharmacokinetics for oral efficacy
The synthesis and structure-activity relationship of a series of benzenesulfonamide indole inhibitors of cPLA2α are described. Substitution of the benzenesulfonamide led to analogues with 50-fold improvement in potency versus the unsubstituted benzenesulfonamide lead compound. Rat pharmacokinetics in a minimal formulation was used to prioritize compounds, leading to the discovery of a potent inhibitor of cPLA2α with oral efficacy in models of rat carrageenan paw edema and Ascaris suum airway challenge in naturally sensitized sheep.
Lee, Katherine L.,Behnke, Mark L.,Foley, Megan A.,Chen, Lihren,Wang, Weiheng,Vargas, Richard,Nunez, Jill,Tam, Steve,Mollova, Nevena,Xu, Xin,Shen, Marina W.H.,Ramarao, Manjunath K.,Goodwin, Debra G.,Nickerson-Nutter, Cheryl L.,Abraham, William M.,Williams, Cara,Clark, James D.,McKew, John C.
p. 1345 - 1358
(2008/09/18)
More Articles about upstream products of 540526-28-1