Document Report Card

ID: ALA1156787

Journal: J Med Chem

Title: Structure-activity relationship studies leading to the identification of (2E)-3-[l-[(2,4-dichlorophenyl)methyl]-5-fluoro-3-methyl-lH-indol-7-yl]-N-[(4,5-dichloro-2-thienyl)sulfonyl]-2-propenamide (DG-041), a potent and selective prostanoid EP3 receptor antagonist, as a novel antiplatelet agent that does not prolong bleeding.

Authors: Singh J, Zeller W, Zhou N, Hategan G, Mishra RK, Polozov A, Yu P, Onua E, Zhang J, Ramírez JL, Sigthorsson G, Thorsteinnsdottir M, Kiselyov AS, Zembower DE, Andrésson T, Gurney ME.

Abstract: The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneous chemical optimization and druglike assessment of prioritized molecules converged on a lead compound 50 (DG-041) that displayed favorable in vitro and functional activities as an inhibitor of human platelet aggregation. This agent is currently in human clinical trials for the treatment of atherothrombosis.

CiteXplore: 19957930

DOI: 10.1021/jm9005912