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-one (7o) was found to be highly potent and possessed a well-balanced combination of these actions in vitro.