Abstract
An exploratory SAR study on a series of potent, non-apamin-displacing 4-(aminomethylaryl)pyrazolopyrimidine K(Ca) channel blockers is described and their selectivity against K(Ca) channel subtypes is reported. The most potent analog, 5-chloro-N-(thiophen-2-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine (24) displayed sub-micromolar activity in both a thallium flux and whole-cell electrophysiology assay and did not displace apamin in a competitive binding study.
MeSH terms
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Apamin / chemistry*
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Binding, Competitive
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Cell Line
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Electrophysiology
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Humans
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Inhibitory Concentration 50
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Models, Chemical
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Potassium Channel Blockers / chemistry*
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Potassium Channels, Calcium-Activated / metabolism
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Protein Isoforms
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Pyrazoles / chemical synthesis*
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Pyrazoles / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Structure-Activity Relationship
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Thallium / chemistry
Substances
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Potassium Channel Blockers
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Potassium Channels, Calcium-Activated
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Protein Isoforms
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Pyrazoles
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Pyrimidines
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Apamin
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Thallium
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pyrimidine