新型1,4-双哌嗪二硫代甲酸[1-取代(1,2,3-三唑)-4]-甲酯类化合物的设计、合成和抗肿瘤活性研究  

Design, Synthesis and Antitumor Study of Novel 1,4-Bispiperazine- carbodithioic Acid [1-Substituted-(1,2,3-triazole)-4]-methyl Esters

作　　者：王盟盟[1] 段迎超[1] 叶先炜[1] 任景丽[1] 余斌[1] 张恩[1] 刘宏民[1] 

机构地区：[1]郑州大学药学院,郑州450001

出　　处：《有机化学》2013年第11期2384-2390,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(Nos.81172937;U1204206);教育部博士点新教师基金(No.20114101120013);中国博士后科学基金(Nos.20100480857;201104402)资助项目~~

摘　　要：为了寻找新型抗肿瘤活性优良的先导化合物,我们以哌嗪、二硫化碳和溴丙炔为原料一锅得哌嗪基二硫代甲酸酯双炔化合物1,再利用"点击化学"合成了未见文献报道的含有1,2,3-三唑和哌嗪二硫代甲酸酯结构单元的1,4-双哌嗪二硫代甲酸[1-取代(1,2,3-三唑)-4-]甲酯类化合物3a^3o.所有化合物结构经1H NMR,13C NMR和HRMS进行了确证.利用噻唑蓝(MTT)法测试了目标化合物对EC-9706,MGC-803,SMMC-7721和MCF-7的体外抗肿瘤活性,部分化合物表现出了较好的抗肿瘤活性,其中化合物3a对MGC-803的抗肿瘤活性与阳性对照氟尿嘧啶相当,对SMMC-7721的抗肿瘤活性优于阳性对照氟尿嘧啶,IC50分别为11.15和14.75μmol/L.In order to find novel lead compounds with promising antitumor activity, a series of novel 1, 4-bispiperazine-carbodithioic acid [1-substituted-（1, 2, 3-triazole）-4]-methyl esters were designed and synthesized. Commercially available pi-perazine reacting with CS2 and propargyl bromide in the presence of Na3PO4·12H2O in one pot gave compound 1, which was further reacted with appropriately substituted azide derivatives by click reaction to afford desired target compounds 3a～3o. The structures were characterized by 1H NMR, 13C NMR and HRMS. The compounds were evaluated for antitumor activity against four selected human tumor cell lines of EC-9706, MGC-803, SMMC-7721 and MCF-7. Several compounds exhibited moderate to potent activity. Particularly, compound 3a was more potent than 5-fluorouracil against MGC-803 and SMMC-7721 with IC50 values of 11.15 and 14.75 μmol/L.

关 键 词：1 2 3-三唑 二硫代甲酸酯 点击化学 抗肿瘤活性 

分 类 号：R914.2[医药卫生—药物化学] R96[医药卫生—药学]