张遵仪, 韩鹏飞, 梁满达, 饶曼人. 原儿茶酸衍生物的化学结构与冠脉流量、心肌耗氧量关系的探讨J. 药学学报, 1980, 15(11): 641-647.
引用本文: 张遵仪, 韩鹏飞, 梁满达, 饶曼人. 原儿茶酸衍生物的化学结构与冠脉流量、心肌耗氧量关系的探讨J. 药学学报, 1980, 15(11): 641-647.
Zhang Zunyi, Han Pengfei, Liang M,a , Rao Manren, . EXPERIMENTAL STUDIES ON RELATIONSHIP OF CHEMICAL STRUCTURE OF PROTOCATECHUIC ACID DEIRVATIVES AND CARDIAC OXYGEN CONSUMPTION AND CORONARY FLOWJ. Acta Pharmaceutica Sinica, 1980, 15(11): 641-647.
Citation: Zhang Zunyi, Han Pengfei, Liang M,a , Rao Manren, . EXPERIMENTAL STUDIES ON RELATIONSHIP OF CHEMICAL STRUCTURE OF PROTOCATECHUIC ACID DEIRVATIVES AND CARDIAC OXYGEN CONSUMPTION AND CORONARY FLOWJ. Acta Pharmaceutica Sinica, 1980, 15(11): 641-647.

原儿茶酸衍生物的化学结构与冠脉流量、心肌耗氧量关系的探讨

EXPERIMENTAL STUDIES ON RELATIONSHIP OF CHEMICAL STRUCTURE OF PROTOCATECHUIC ACID DEIRVATIVES AND CARDIAC OXYGEN CONSUMPTION AND CORONARY FLOW

  • 摘要: 本文研究原儿茶酸的三类衍生物,(1)原儿茶酸的四甲基吡嗪盐,(2)原儿茶酸与β-阻断剂有效基团相结合的衍生物,(3)原儿茶酸的同分异构物。利用测定猫冠状窦流量、心肌耗氧量、动静脉氧差、血压、心率等指标以及大、小鼠整体耐缺氧以探讨改变原儿茶酸的化学结构与药理作用间的关系。适量的吡嗪原儿茶酸在轻度增加冠脉流量的同时能较明显降低心肌耗氧量,而同剂量的四甲基吡嗪则明显增加心肌耗氧量,吡嗪原儿茶酸降低心肌耗氧量的程度较单用原儿茶酸约强14倍。四甲基吡嗪增强了原儿茶酸降低心肌耗氧量的作用。而原儿茶酸又能使四甲基吡嗪从增加心肌耗氧量反转为降低心肌耗氧量。原儿茶酸与β-阻断剂有效基团相结合合成的7704(异)、7704(叔)的作用基本上与β-阻断剂相似,但作用强度较心得宁弱。原儿茶酸同分异构物2,5-二羟基苯甲酸与2,6-二羟基苯甲酸虽能明显延长整体动物耐缺氧,但对猫心肌耗氧量则无明显作用。

     

    Abstract: In an earlier paper we reported that administration of protocatechuic acid (PAC), isolated from leaves of Ilex chinensis Sims, decreased myocardial oxygen consumption in cats and increased tolerance to anoxia in rat heart-lung preparations. In this paper, three groups of PAC derivatives were studied on their influence on cardiac oxygen consumption and coronary flow in open chest cats. The first group of compound, PAC-1, was obtained by neutralizing PAC with tetramethylpyrazine. PAC-1 decreased the myocardial oxygen consumption with a potency higher than that of PAC, but didn't influence the coronary flow. On the contrary, tetramethyl pyrazine at the same dosage increased the coronary flow and didn't decrease the myocardial oxygen consumption. Three compounds of the second group were PAC derivatives bearing various functionary moieties of β-receptor blocking agents, namely: 7704-1: 1-(2-methoxy-4-methoxycarbonyl-1-phenoxy) 3-isopropyl-amino-2-propanol, 7704-T: 1-(2-methoxy-4-methoxycarbonyl)-3-tertiary butylamino-2-propanol, 7704-H: 1-(2-methoxyl-4-methoxycarbonyl-1-phenoxy)-3-(3,4-dimethoxy phenyl ethyl amino)-2-propanol. Their effects on myocardial oxygen consumption, coronary flow, arterial pressure and heart rate were similar to that of praetolol but weaker in potency. Two compounds of the third group were isomers of PAC, namely, 2,5-dihydrobenzoic acid and 2,6-dihydrobenzoic acid. Both drugs increased tolerance to anoxia in intact mice, but didn't influence tbe cardiac oxygen consumption and coronary flow.

     

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