抗癌药研究 Ⅰ.谷氨酰胺衍生物的合成
POTENTIAL ANTICANCER AGENTS Ⅰ. SYNTHESIS OF DERIVATIVES OF GLUTAMINE AND RELATED COMPOUNDS
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摘要: 企图由抑制谷氨酰胺酶的活性来寻找抗肿瘤药物,因而合成了邻苯二甲酰谷氨酰胺及邻苯二甲酰谷氨酸酯衍生物以及相应的谷氨酰胺及谷氨酸酯衍生物等23个化合物。所有化合物系从邻苯二甲酰谷氨酸酐与相当的胺或醇进行反应制备的,然后在碳酸鈉水溶液中用肼水解,除去邻苯二甲酰基.化合物系列I中1,2,5,7,8,9,10有抑制谷氨酰胺酶的活性,I8对动物肿瘤有效,但不带邻苯二甲酰基的谷氨酰胺衍生物則无活性.Abstract: Twenty three glutamine derivatives (5-N-substituted amides and 5-alkylesters of phthalimido-α-aminoglutarid acid) were synthesized for anticancer and glutaminase inhibitory tests. These compounds were prepared from a-phthalimido-glutaric anhydride and appropriate amines and alcohols. The phthalyl group was removed by hydrolysis with aqueous hydrazine hydrate and sodium carbonate solution. Compound I8 shows significant inhibitory activity against S 180 and several other animal tumors, while compounds I1,2,5,7-10 inhibit the activity of glutaminase. On the contrary, compounds of type II are inactive.
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