Novel calcium antagonists with both calcium overload inhibition and antioxidant activity. 1. 2-(3, 5-di-tert-butyl-4-hydroxyphenyl)-3-(aminopropyl)thiazolidinones.
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.
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Company, Ltd., 135, 1-Chome Komakado, Gotemba City, Shizuoka 412-8513, Japan.
T
T
Kato
T
T
Ozaki
K
K
Tamura
Y
Y
Suzuki
M
M
Akima
N
N
Ohi
D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013025:Glycine max / Q000201:enzymology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D053778:Thiazolidines; D014701:Veratridine / Q000633:toxicity
D000975:Antioxidants; C115426:CP 060; D002121:Calcium Channel Blockers; D008077:Lipoproteins, LDL; D010636:Phenols; D013844:Thiazoles; D053778:Thiazolidines; D014701:Veratridine; D008084:Lipoxygenase; D002118:Calcium