Abstract
L-Type Ca(2+) channels (LTCCs) play a key role in the regulation of vascular smooth muscle contraction, and substances that interfere with their function (Ca(2+) channel blockers) are widely used in the therapy of hypertension. Here, we report anthracene-maleimide derivatives as new LTCC blockers. Among these, 3, lacking intracellular effects, was investigated in more detail. The results show that 3 binds preferentially to inactivated LTCCs, directly interacting with the pore-forming subunit of the channel.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anthracenes / chemical synthesis*
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Anthracenes / chemistry
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Anthracenes / pharmacology
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Arteries / drug effects
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Arteries / physiology
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Calcium Channel Agonists / pharmacology
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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, L-Type / physiology*
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Drug Design
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In Vitro Techniques
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Maleimides / chemical synthesis*
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Maleimides / chemistry
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Maleimides / pharmacology
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Muscle Contraction / drug effects
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Muscle, Skeletal / metabolism
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / physiology
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Protein Subunits / physiology
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Rabbits
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Radioligand Assay
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Rats
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Structure-Activity Relationship
Substances
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Anthracenes
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Calcium Channel Agonists
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Calcium Channel Blockers
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Calcium Channels, L-Type
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Maleimides
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Protein Subunits