Abstract
The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1H-pyrazol-3-yl]methyl}-3-fluorocyclopentanamine, which exhibits high intrinsic potency and selectivity against other opioid receptors and hERG potassium channel.
MeSH terms
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Cyclopentanes / chemical synthesis
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Cyclopentanes / chemistry*
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Cyclopentanes / pharmacology
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Drug Discovery
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels / metabolism
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Humans
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Narcotic Antagonists*
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Nociceptin Receptor
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology
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Receptors, Opioid / metabolism
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Structure-Activity Relationship
Substances
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Cyclopentanes
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ERG1 Potassium Channel
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Ether-A-Go-Go Potassium Channels
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KCNH2 protein, human
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N-((1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1H-pyrazol-3-yl)methyl)-3-fluorocyclopentanamine
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Narcotic Antagonists
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Pyrazoles
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Receptors, Opioid
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Nociceptin Receptor
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OPRL1 protein, human