Abstract
We synthesized and evaluated a series of 5-(1-methyl-3-trifluoromethyl-1H-pyrazol-5-yl)-2-thiophenecarboxamides to identify potent inhibitors of calcium-release-activated calcium (CRAC) channels with greater selectivity than voltage-operated calcium (VOC) channels. These efforts resulted in identification of compounds 22 and 24. The former exhibits highly potent and selective CRAC channel inhibitory activity, and the latter inhibited phytohemagglutinin-induced interleukin-2 production by Jurkat T lymphocytes and concanavalin A-induced hepatitis in mice.
MeSH terms
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Amides / chemical synthesis*
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Amides / chemistry
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Amides / pharmacology*
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Animals
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Calcium Channel Blockers / chemical synthesis*
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / pharmacology*
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Calcium Channels / drug effects
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Calcium Channels / metabolism
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Drug Evaluation, Preclinical
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Female
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Humans
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Interleukin-2 / biosynthesis
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Jurkat Cells
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Mice
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Mice, Inbred BALB C
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PC12 Cells
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Quantitative Structure-Activity Relationship
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Rats
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Thiophenes / chemical synthesis*
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Thiophenes / chemistry
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Thiophenes / pharmacology*
Substances
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Amides
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Calcium Channel Blockers
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Calcium Channels
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Interleukin-2
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Thiophenes