Kato T, Ozaki T, Tamura K, Suzuki Y, Akima M, Ohi N
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Company, Ltd., 135, 1-Chome Komakado, Gotemba City, Shizuoka 412-8513, Japan.
J Med Chem. 1998 Oct 22;41(22):4309-16. doi: 10.1021/jm980335f.
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.
为了探索具有强效抗缺血活性的新型钙拮抗剂，合成了一系列2-(3,5-二叔丁基-4-羟基苯基)-3-(氨丙基)噻唑烷酮。设计这些化合物的目的是，除了具有Ca2+拮抗活性外，还能在一个分子中兼具预防Ca2+过载和抗氧化活性。分别使用K+去极化的大鼠主动脉、藜芦定诱导的大鼠心肌细胞Ca2+过载模型以及大豆脂氧合酶诱导的兔低密度脂蛋白脂质过氧化模型，对这三种活性进行了评估。特别地，发现2-(3,5-二叔丁基-4-羟基苯基)-3-[3-[N-甲基-N-[2-[3,4-(亚甲二氧基)苯氧基]乙基]氨基]丙基]-1,3-噻唑烷-4-酮(7o)具有高效性，并且在体外具有这些作用的良好平衡组合。
