抗心肌缺血药2,6-二甲基-4-双取代苯基-1,4-二氢吡啶-3,5-二羧酸酯的合成

SYNTHESIS OF 2,6- DIMETHYL -4-DISUBSTITUTED PHENYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATES AS ANTIMYOCARDIAL ISCHEMIC AGENTS

本文报道了9个新的2,6-二甲基-4-双取代苯基-1,4-二氢吡淀-3,5-二羧酸酯的合成。初步药理试验表明:化合物I_6具有较强的抑制KCl诱发兔主动脉条的收缩作用,增加冠脉血流量和心输出量,降低心肌耗氧量;增强小鼠抗缺氧能力;对大鼠心肌缺血有保护作用;能缩小兔缺血心肌再灌流引起的心肌梗塞范围。

Nine title compounds were synthesized as potential antimyocardial ischemic agents. After screening, some of these compounds were found to exhibit calciumblocking activity. Among them, the antagonism of compound I_6 (diethyl 4- {3- methoxy - 4 - [ (2 - hydroxy - 3 - isopropylamino )propoxy] phenyl}- 1,4 - dihydropyridine- 3,5-dicarboxylates) was the most potent in the potassium-stimulated rabbit aortic strip.Compound I_6 was subjected to further pharmacological assay, and it was shown to increase coronary flow and cardiac output of isolated rabbit heart, reduce myocardial oxygen consumption, decrease myocardial infarct size of rat, and increase the tolerance of mice to hypoxia.