Heterocyclic 1,7-disubstituted indole sulfonamides are potent and selective human EP3 receptor antagonists |
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| Authors: | Georgeta Hategan Alexandre M Polozov Wayne Zeller Hua Cao Rama K Mishra Alex S Kiselyov Jose Ramirez Guðrún Halldorsdottir Þorkell Andrésson Mark E Gurney Jasbir Singh |
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| Institution: | 1. Medicinal Chemistry Department, deCODE Chemistry, Inc., 2501 Davey Road, Woodridge, IL 60517, United States;2. deCODE Genetics, Inc., Reykjavik, Iceland |
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| Abstract: | We have developed a pharmacophore model for the EP3 receptor antagonists based on its endogenous ligand PGE2. This ligand-based design yielded a series of novel peri-substituted 4.3.0] bicyclic aromatics featuring 1-alklyaryl 7-heterocyclic sulfonamide substituents. The synthesized molecules are potent antagonists of human EP3 receptor in vitro and show inhibition of rat platelets aggregation. Optimized derivatives display high selectivity over IP, FP, and other EP receptor panels. |
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