巯基苯甲酰-甘氨酰-甘氨酸衍生物的合成

SYNTHESIS OF DISULFIDES OF N-[N-(2-MERCAPTOBENZOYL)-GLYCYL]-N-ALKYL/ARYL-GLYCINE

为寻找新的口服有效的血管紧张素转化酶(ACE)抑制剂,以硫代水杨酸双硫化合物为原料制得N,N′-(2,2′-二硫-双-苯甲酰)-双-甘氨酸,在DCC作用下与N-取代甘氨酸缩合合成了8个N,N′-[N,N′-(2,2′-二硫-双-苯甲酰)-双-甘氨酰]-N,N′-双-烃基取代-双-甘氨酸类化合物(DL_(1-8))。化合物DL_5和DL_8对大鼠ACE抑制活性较强。

Eight compounds of N, N'-[ N,N'-(2,2/-disulfidibenzoyl)-diglycyl]-N, N'-dialkyl/diaryi-diglycines (DL_(1-8)) were designed and synthesized as new angiotensin-converting enzyme inhibitors (ACEI). 2-Mereaptobenzoyl glycine disulfide was prepared by the condensation of 2, 2′-dithiobisbenzoyl dichloride with methyl glycinate, followed by reduction, hydrolysis and oxidation. Compounds (DL_(1-8)) were prepared by the condensation of 2-mereaptobenzoyl glycine disulfide with ethyl N-alkyl/aryl glycinate, followed by reduetion, hydrolysis and oxidation. In preliminary pharmacological test in rats, the compounds showed varied degree of inhibitory activity to ACE, and DL, and were found to be more active.