Abstract
A series of potent and selective EP(3) receptor antagonists are described. Utilizing a pharmacophore model developed for the EP(3) receptor, a series of 3,4-disubstituted indoles were found to be efficient ligands for this target. These compounds showed high selectivity over IP, FP and other EP receptors. An optimized molecule 7c featured a sound profile and potency in the functional rat and human platelet aggregation assays.
MeSH terms
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Acrylamides / chemical synthesis*
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Acrylamides / metabolism*
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Acrylamides / pharmacology
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Dogs
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical / methods
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Drug Stability
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Haplorhini
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Humans
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Indoles / chemical synthesis*
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Indoles / metabolism*
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Indoles / pharmacology
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Mice
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Rats
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Receptors, Prostaglandin E / antagonists & inhibitors*
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Receptors, Prostaglandin E / metabolism
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Receptors, Prostaglandin E, EP3 Subtype
Substances
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Acrylamides
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Indoles
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PTGER3 protein, human
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Ptger3 protein, mouse
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Ptger3 protein, rat
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP3 Subtype