冠心病药物的研究——Ⅰ.带有取代胺基乙酰胺基的环状化合物的合成

心绞痛是由于心肌对氧的供需失去平衡而引起暂时性缺血的临床症状。很多治疗心绞痛的药物可以增加心肌缺氧的耐受力。因此寻找能耐缺氧的化合物对冠心病的治疗可能具有实用价值与理论意义。鉴于维生素B₁₅能改善缺氧的能力,以及利多卡因有抗心律不齐的作用。作者将两类化合物进行拼合,合成了一系列带有取代胺基乙酰胺基的环状化合物。合成方法是以取代的苯胺或醇与氯乙酰氯缩合,再与各种胺类反应,即形成所需产物。药理试验结果显示,其中许多化合物具有良好的耐缺氧作用,尤以异丙胺乙酰(2,4-二甲基苯胺)(15)、异丙胺乙酰苯胺盐酸盐(19)及二乙胺乙酰(3,4-二氯苯胺)盐酸盐(11)的作用更为显著,而4,6-双(异丙胺乙酰胺基)1,3-二甲苯(61)、4,6-双(仲丁胺乙酰胺基)1,3-二甲苯(62)及4,6-双(二异丙胺乙酰胺基)1,3-二甲苯(60)虽无耐缺氧作用,但却具有较强的抗心律不齐作用。

STUDIES ON DRUGS FOR CORONARY HEART DISEASE (Ⅰ) SYNTHESIS OF RING COMPOUNDS WITH SUBSTITUTED AMINO-ACETYL-AMINO GROUP

Angina pectoris is a clinical syndrome caused by transient myocardial ischemia which is due to an imbalance between myocardial oxygen supply and demand. Many drugs for the treatment of angina pectoris have been shown to increase myocardial tolerance of hypoxia, so it is of theoretical significance and practical value to search for compounds for improving the myocardial tolerance of hypoxia. In view of the fact that vitamin B₁₅ can improve the tolerance of hypoxia and Lidocaine possesses antiarrythmic activity, a series of ring compounds carrying substituted amino acetylamino groups were synthesized by combining these two structures in one molecule. These compounds were synthesized by condensation of suitable aniline or alcohol with chloroacetylchloride, followed by reacting with corresponding amines. Preliminary pharmacological examination revealed that some of the compounds especially ω-isopropylamino-2,4-dimethylacetanilide (15), the hydrochloride of ω-isopropylamino acetanilide (19) as well as the hydrocbloride of ω-diethylamino-3,4-dichloro-acetanilide (11) showed significant activity to improve the tolerance of hypoxia for heart, while, 4,6-Bis (isopropyl-amino acetylamino) 1,3-xylol (61), 4,6-Bis-(s-butylamino acetylamino) 1,3-xylol (62), 4,6-Bis (diisopropylaminoacetyl-amino) 1,3-xylol (60) did not exhibit such activity but possessed a strong antiarrythmic action.