1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究  

Design,Synthesis and Biological Activities of Compounds Containing 1,3,4-Oxadiazole or 1,3,4-Thiadiazole

作　　者：鄢龙家 黎永良[1] 邓明高 陈安超 杜志云[1] 董长治[1,3] 陈惠雄 Yan Longjia;Li Yongliang;Deng Minggao;Chen Anchao;Du Zhiyun;Dong Changzhi;Chen Huixiong(Faculty of Light Industry and Chemical Engineering,Guangdong University of Technology,Guangzhou,510006,China;Biomedicale,Universite Paris Descartes,75006 Paris,France;Universite Paris Diderot,75013 Paris,France)

机构地区：[1]广东工业大学轻工化工学院,广州510006 [2]巴黎笛卡尔大学生物医学系,巴黎75006 [3]巴黎狄德罗大学,巴黎75013

出　　处：《有机化学》2020年第3期731-739,共9页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.21672043)资助项目。

摘　　要：为了寻求新型抗肿瘤药物,设计并合成了一系列新型1,3,4-噁二唑和1,3,4-噻二唑衍生物,对这些化合物在人类四种癌细胞:B-16(皮肤黑色素瘤细胞)、PC-3(人前列腺癌细胞)、U87(人原发性胶质母细胞瘤细胞)和A549(人非小细胞肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性,尤其是5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(2-甲氧基苯基)酰胺(8b)]和5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(4-甲氧基苯基)酰胺(8c)],对四种癌细胞都显示出较高的抗肿瘤活性,其抑制活性均优于阳性对照达沙替尼,随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.In order to find new anti-tumor drugs,a series of novel 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives were designed and synthesized.The target compounds were evaluated for antitumor activity in vitro on four human cancer cell lines including B-16(skin melanoma cells),PC-3(human prostate cancer cells),U87(human primary glioblastoma celis)and A549(human non-small cell lung cancer cells).The results displayed that some of the compounds had good activities,especially,(5(-6-(4-(2-hydroxyethyl)piperazin-l-yl)-2-methylpyrimidin-4-yl)amino)-N-(2-methoxyphenyl)-1,3,4-thiadiazole-2-carboxamide(8b)and 5-((6-(4-(2-hydroxyethyl)piperazin-l-yl)-2-methylpyrimidin-4-yl)amino)-N-(4-methoxyphenyl)-1,3,4-thiadiazole-2-carboxamide(8c)showed high antitumor activities against four cancer cell lines,which was better than dasatinib.These compounds were further studied for their possible target of tumor suppression.

关 键 词：1 3 4-噁二唑 1 3 4-噻二唑 抗肿瘤 Src抑制剂 

分 类 号：O626[理学—有机化学] TQ463.5[理学—化学]