Abstract
A series of 4-isoxazolyl-1,4-dihydropyridines bearing lipophilic side chains at the C-5 position of the isoxazole ring have been prepared. The calcium channel antagonistic activity of these compounds has been evaluated. A hypothetical model for binding of these compounds in the calcium channel is proposed, and the validity of this model is evaluated based on the SAR of this series of calcium binding, especially for the two most active derivatives, 1a, g. The solid-state structure for the most active compound, 1a, has also been determined, and its important features are reported.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Binding, Competitive
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Calcium Channel Blockers / chemical synthesis*
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Calcium Channel Blockers / chemistry
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Calcium Channel Blockers / metabolism
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Calcium Channels / chemistry
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Calcium Channels / metabolism
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Guanidines / chemical synthesis*
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Guanidines / chemistry
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Guanidines / metabolism
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Guinea Pigs
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In Vitro Techniques
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Models, Molecular
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Myocardium / metabolism
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Radioligand Assay
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Structure-Activity Relationship
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X-Ray Diffraction
Substances
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1-(4-(4-phenyl-1,3-butadienyl)benzyl)guanidinium
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Calcium Channel Blockers
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Calcium Channels
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Guanidines