1,4-苯并二氮-3-取代氨基乙酸酯类化合物的合成

本文报道了一系列1,4-苯并二氮(艹卓)-3-取代氮基乙酸酯类化合物的合成。A_3与取代氨基乙酸直接酯化制备最终产物,用DCC作缩合剂时只分离到反应的中间体;改用活性更大的1,1′-碳酰二咪唑作缩合剂,反应获得成功。合成的新化合物能溶于水。放射配体-受体抑制试验表明,这些化合物与苯并二氮革受体的亲和力较强,IC_(50)在10~(-8)～10~(-10)之间,其中A_9与苯并二氮(艹卓)受体的亲和力比氟安定高一个数量级,比安定高两个数量级。

SYNTHESIS OF 3-SUBSTITUTED AMINOACETIC ACID ESTERS OF 1,4-BENZODIAZEPINE

Eight 3-substituted aminoacetic acid esters of 1,4-benzodiazepine were synthesized. Intermediate A_3 was obtained by oxidation of A_1 with lead tetraacetate and subsequent hydrolysis of the oxidation product. Esterification of A_3 with chloroacetyl chloride produced A_6. The esterification of A_3 and substituted aminoacetic acids with N, N'-dicyclohexylcarbodiimide (DCC)as a catalyst afforded only reaction intermediates (ca A_3). Their structures were identified. The end products were obtained when the more active 1,1'-carbonyldiimidazole was used. All synthesized compounds were water-soluble. The labelled ligand-receptor inhibition tests showed that these compounds possessed higher affinity to the benzodiazepine receptor. The range of IC_(50) was 10~(-8)10~(-10). Among them A_9 had the highest affinity.