N-取代多亚甲基二甲酰胺类癌细胞分化诱导剂的合成  

SYNTHESIS OF N-SUBSTITUTED POLYMETHYLENE DICARBOXAMIDES AS INDUCERS OF DIFFERENTIATION

作　　者：文晓霞[1] 扈志勇[1] 郭佃顺[1] 王慧才[1] 赵彦伟[1] 

机构地区：[1]山东医科大学药学系,济南250012

出　　处：《药学学报》1993年第3期234-237,共4页Acta Pharmaceutica Sinica

摘　　要：癌细胞分化诱导剂通过诱导癌细胞分化成熟,降低其恶性程度以抑制肿瘤,对正常细胞无毒性,是理想的抗肿瘤剂。人工合成的六亚甲基双乙酰胺(HMBA)是迄今较理想的分化诱导剂,体外实验在5 mmol/L时能诱导99%以上的小鼠红白血病细胞(MELC)分化成熟,对HL-60人早幼粒白血病细胞及小鼠畸胎癌,小鼠神经母细胞瘤、人淋巴肉瘤等多种细胞均有诱导分化作用,现已进入临床研究。但最近报道HMBA用于临床有降低血小板数,增加血液酸度,抑制大脑功能等毒付作用。N-Alkyl polymethylene dicarboxamides are known potent inducers of erythroid differentiation in murine erythroleukemia cells. The most active inducer N, N, N', N'-tetramethyl-1, 6-hexane-dicarboxamide has the same effectiveness as HMBA which has entered clinical trials as a differentiating agent. These compounds also have inducing activity in HL-60 human promyelocytic leukemia cells. In this paper, the synthesis of a series of N,N'-bis[2-(2-thiazolinyl)], N,N'-bis [5-(1-methyl-2-pyridonyl)], N, N'-bis [3-(1- phenyl- 5- pyrazolonyl )] polymethylene dicarboxamides and 3,3'-(polymethylene dicarbonyl)bis(1-methyl-2-imidazolidine-thiones) is reported. The inducing activities of the compounds were evaluated in vitro with HL-60 human promyelocytic leukemia cell line. Among them, N, N'-bis[-2- (2-thiazolinyl)]-1,8-octamethylene-dicarboxamide (Ⅰ_4) and N, N'-bis[5- (1-methyl- 2-pyridonyl)]-1,6-hexamethylenedicarboxamide (Ⅱ_3) were shown to be relatively effective inducers of differentiation.

关 键 词：二甲酰胺 分化 诱导 癌细胞 

分 类 号：R979.1[医药卫生—药品]