Abstract
A series of peri-substituted [4.3.0] bicyclic non-aromatic heterocycles have been identified as potent and selective hEP(3) receptor antagonists. These molecules adopt a hair-pin conformation that overlaps with the endogenous ligand PGE(2) and fits into an internally generated EP(3) pharmacophore model. Optimized compounds show good metabolic stability and improved solubility over their corresponding bicyclic aromatic analogs.
MeSH terms
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Alprostadil / analogs & derivatives
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Alprostadil / metabolism
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Animals
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CHO Cells
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Chemistry, Pharmaceutical / methods
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Cricetinae
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Cricetulus
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Drug Design
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Humans
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Indoles / chemical synthesis*
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Indoles / pharmacology*
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Inhibitory Concentration 50
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Ligands
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Magnetic Resonance Spectroscopy
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Prostaglandins / chemistry
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Receptors, Prostaglandin E / antagonists & inhibitors*
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Receptors, Prostaglandin E / chemistry
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Receptors, Prostaglandin E, EP3 Subtype
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Sulfonamides / chemistry
Substances
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Indoles
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Ligands
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PTGER3 protein, human
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Prostaglandins
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP3 Subtype
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Sulfonamides
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prostaglandin E3
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Alprostadil