几种新型4-芳酰基-1-亚硝基肼甲酰胺的合成及其抗肿瘤活性

Synthesis and antitumour activity of several new 4-aroyl-1-nitrosohydrazinecarboxamides.

作者信息

Gugova R, Topakbashian V, Lozeva S, Dimov S, Golovinsky E

机构信息

Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria.

出版信息

Drugs Exp Clin Res. 1997;23(2):71-5.

PMID:9309382

Abstract

Six new analogues of nitrosoureas containing aroylhydrazine residue have been synthesized: (I) 4-(2-fluorobenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxamide++ +; (II) 4-(4-bromobenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxam ide; (III) 4-(4-hydroxybenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarboxamide+ ++; (IV) 4-(3-methoxybenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarbox amide; (V) 4-(4-methoxybenzoyl)-1-(2-chloroethyl)-1-nitrosohydrazinecarbox amide; (VI) 4-(4-fluorophenylacetyl)-1-(2-chloroethyl)-1-nitrosohydrazineca rboxamide. All six compounds showed a dose-dependent in vivo activity against leukaemias L1210 and P388. Compounds I and III were soluble in water. The antitumour effects were highly expressed in compound III, yielding a T/C% value of 402% in leukaemia P388, and in compound VI, 356% in leukaemia L1210.

摘要

已合成六种含有芳酰肼残基的亚硝基脲类似物

（I）4-（2-氟苯甲酰基）-1-（2-氯乙基）-1-亚硝基肼甲酰胺；（II）4-（4-溴苯甲酰基）-1-（2-氯乙基）-1-亚硝基肼甲酰胺；（III）4-（4-羟基苯甲酰基）-1-（2-氯乙基）-1-亚硝基肼甲酰胺；（IV）4-（3-甲氧基苯甲酰基）-1-（2-氯乙基）-1-亚硝基肼甲酰胺；（V）4-（4-甲氧基苯甲酰基）-1-（2-氯乙基）-1-亚硝基肼甲酰胺；（VI）4-（4-氟苯基乙酰基）-1-（2-氯乙基）-1-亚硝基肼甲酰胺。所有六种化合物对白血病L1210和P388均表现出剂量依赖性的体内活性。化合物I和III可溶于水。化合物III的抗肿瘤作用高度显著，在白血病P388中T/C%值为402%；化合物VI在白血病L1210中T/C%值为356%。