Abstract
3,4-Dihydroquinazoline analogues substituted by N-methyl-N-(5-pyrrolidinopentyl)amine at the 2-position were synthesized and their blocking effects were evaluated for T- and N-type calcium channels. Compound 11b (KYS05080), compared to mibefradil (IC50=1.34+/-0.49 microM), was about 5-fold potent (IC50=0.26+/-0.01 microM) for T-type calcium channel (alpha1G) blocking and its selectivity of T/N-type was also improved (7.5 versus 1.4 of mibefradil).
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium Channel Blockers / chemical synthesis*
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Calcium Channel Blockers / pharmacology*
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Calcium Channels, N-Type / drug effects
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Calcium Channels, T-Type / drug effects*
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Cell Line, Tumor
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Crystallography, X-Ray
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Mibefradil / pharmacology
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Models, Molecular
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Oocytes / drug effects
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Oocytes / metabolism
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Pyrrolidines / chemical synthesis*
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Pyrrolidines / pharmacology*
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Quinazolines / chemical synthesis*
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Quinazolines / pharmacology*
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Xenopus
Substances
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Calcium Channel Blockers
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Calcium Channels, N-Type
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Calcium Channels, T-Type
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Indicators and Reagents
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Pyrrolidines
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Quinazolines
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Mibefradil