Abstract
A series of 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3-(aminopropyl)thiazolidinones was synthesized in order to explore novel calcium antagonists with potent antiischemic activity. These compounds were designed to have, in addition to Ca2+ antagonistic activity, both Ca2+ overload prevention and antioxidant activity in one molecule. These three kinds of activity were evaluated by using a K+-depolarized rat aorta, a veratridine-induced Ca2+ overload model of rat cardiomyocytes, and a soybean lipoxygenase-induced lipid peroxidation model of rabbit low-density lipoprotein, respectively. In particular, 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3-[3-[N-methyl-N-[2-[3, 4-(methylenedioxy)phenoxy]ethyl]amino]propyl]-1,3-thiazolidin-4-on e (7o) was found to be highly potent and possessed a well-balanced combination of these actions in vitro.
MeSH terms
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Animals
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Antioxidants / chemical synthesis*
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Antioxidants / chemistry
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Antioxidants / pharmacology
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / metabolism
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Calcium / antagonists & inhibitors*
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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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Glycine max / enzymology
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Heart / drug effects
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In Vitro Techniques
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Lipid Peroxidation / drug effects
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Lipoproteins, LDL / metabolism
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Lipoxygenase / metabolism
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Male
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Myocardium / cytology
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Myocardium / metabolism
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Phenols / chemical synthesis*
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Phenols / chemistry
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Phenols / pharmacology
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Rabbits
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Rats
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Thiazoles / chemical synthesis*
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Thiazoles / chemistry
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Thiazoles / pharmacology
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Thiazolidines
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Veratridine / toxicity
Substances
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Antioxidants
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CP 060
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Calcium Channel Blockers
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Lipoproteins, LDL
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Phenols
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Thiazoles
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Thiazolidines
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Veratridine
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Lipoxygenase
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Calcium