Abstract
A high-throughput screen targeting the EP(1) receptor identified non-acidic glycine sulfonamide derivative 2a with a pK(i) of 6.2. Analogue synthesis allowed a thorough investigation of the structure-activity relationship (SAR) and led to a 100-fold increase in recombinant potency.
MeSH terms
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Animals
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CHO Cells
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Cell Membrane / metabolism
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Chromatography, High Pressure Liquid
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Cricetinae
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Cricetulus
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Cytochrome P-450 Enzyme System / metabolism
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Dinoprostone / metabolism
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Drug Evaluation, Preclinical
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Glycine Agents / chemical synthesis*
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Glycine Agents / pharmacology*
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Humans
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Indicators and Reagents
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Receptors, Prostaglandin E / antagonists & inhibitors*
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Receptors, Prostaglandin E, EP1 Subtype
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Sulfonamides / chemical synthesis*
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Sulfonamides / pharmacology*
Substances
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Glycine Agents
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Indicators and Reagents
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PTGER1 protein, human
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Receptors, Prostaglandin E
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Receptors, Prostaglandin E, EP1 Subtype
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Sulfonamides
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Cytochrome P-450 Enzyme System
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Dinoprostone