含1,2-苯并噻嗪结构的[1,3,4]噻二唑并[3,2-a][1,3,5]三嗪衍生物的合成及其抗肿瘤活性  

Synthesis and antitumor activities of 1,2-benzothiazines[1,3,4]thiadiazolo[3,2-a][1,3,5]triazin derivatives

作　　者：赵小美 王新 汲霞 张华 张平平 胡国强[2] ZHAO Xiaomei;WANG Xin;JI Xia;ZHANG Hua;ZHANG Pingping;HU Guoqiang(College of Pharmacy,Qilu Medical University,Zibo 255300;Institute of Pharmacy,Henan University,Kaifeng 475001,China)

机构地区：[1]齐鲁医药学院药学院,淄博255300 [2]河南大学药物研究所,开封475001

出　　处：《中国药科大学学报》2020年第1期24-28,共5页Journal of China Pharmaceutical University

基　　金：山东省高校科研计划资助项目(No.J18KB122);齐鲁医药学院应用药学科研创新平台资助项目(No.2018ZBXC423)。

摘　　要：以吡罗昔康合成中间体(CAS:35511-15-0)为原料,利用活性拼接等药物设计原理,设计并合成了9个结构新颖的目标化合物,其结构经1H NMR、MS等表征。通过测定对胰腺癌细胞Capan-1、白血病细胞L1210和人肝癌细胞SMMC-7721的抑制活性,评价目标化合物的体外抗肿瘤活性。结果表明,化合物6f(IC50=2.4±0.5μmol/L)对胰腺癌细胞Capan-1表现出较好的抑制活性;化合物6h(IC50=5.4±0.2μmol/L)对白血病细胞L1210表现出较好的抑制活性;化合物6g(IC50=3.8±0.2μmol/L)对人肝癌细胞SMMC-7721表现出较好的抑制活性。初步的抗肿瘤活性实验结果表明,将吡罗昔康3位的侧链替代为噻二唑并三嗪侧链,对提高该类化合物的抗肿瘤活性有一定的作用。Based on the drug design principle of reactive functional group splicing,nine novel title compounds were designed and synthesized with piroxicam intermediate as the starting material.Their structures were characterized by 1H NMR and MS analysis.The in vitro antitumor activity evaluation suggested that compounds 6f,6h and 6g exhibited good inhibitory reactivity on pancreatic cancer cell line Capan-1(IC50=2.4±0.5μmol/L),leukemia cell line L1210(IC50=5.4±0.2μmol/L),and human liver cancer cell line SMMC-7721(IC50=3.8±0.2μmol/L),respectively.The introduction of thiadiazolo[3,2-a]triazine side chain could improve the antitumor activity of these compounds.

关 键 词：[1 3 4]噻二唑并[3 2-a][1 3 5]三嗪 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]