喹唑啉类作为二氢叶酸还原酶抑制剂。3. 蝶酸和异蝶酸类似物。

Quinazolines as inhibitors of dihydrofolate reductase. 3. Analogs of pteroic and isopteroic acids.

作者信息

Hynes J B, Buck J M, D'Souza L, Freisheim J H

出版信息

J Med Chem. 1975 Dec;18(12):1191-4. doi: 10.1021/jm00246a004.

Abstract

A series of 19 quinazoline analogs of pteroic and isopteroic acid was prepared with particular emphasis being placed upon carboxylic acid esters. Each compound was evaluated as an inhibitor of the dihydrofolate reductases from rat liver as well as from Streptococcus faecium. Several of the more potent inhibitors were found to be inactive against L1210 leukemia in mice at low dose levels and were lethal to mice at 100 mg/kg. Six compounds were also evaluated for antimalarial activity against Plasmodium berghei in mice. Three of these were found to be curative at higher levels, while the remaining compounds were found to be toxic.

摘要

制备了一系列19种蝶酸和异蝶酸的喹唑啉类似物，特别强调了羧酸酯。每种化合物都作为大鼠肝脏和粪肠球菌二氢叶酸还原酶的抑制剂进行了评估。发现几种更有效的抑制剂在低剂量水平对小鼠L1210白血病无活性，而在100mg/kg时对小鼠致死。还评估了六种化合物对小鼠伯氏疟原虫的抗疟活性。其中三种在较高剂量时具有治愈作用，而其余化合物则有毒性。