4-二苯基亚甲基色满类化合物的设计合成及抗肿瘤活性评价  

Design,synthesis and antitumor activity evaluation of 4-(diphenylmethylene)chroman derivatives

作　　者：童丰 侯世澄 张德良 王世辉[2] 李阳[2] 周晓光 胡春[2] TONG Feng;HOU Shi-cheng;ZHANG De-liang;WANG Shi-hui;LI Yang;ZHOU Xiao-guang;HU Chun(Beijing Chengji Pharmaceutical Co.,Ltd.,Beijing 101301,China;Key Laboratory of Structure-Based Drugs Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)

机构地区：[1]北京诚济制药股份有限公司,北京101301 [2]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《中国药物化学杂志》2022年第12期901-908,共8页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21072130)。

摘　　要：目的设计并合成具有组织特异性的4-二苯基亚甲基色满类化合物,以期发现高选择性的雌激素受体拮抗剂。方法在保留三苯乙烯基本骨架的基础上,利用生物电子等排原理,对他莫昔芬及其类似物进行结构修饰,设计并合成结构对称的4-二苯基亚甲基色满类化合物。以人乳腺癌细胞株MCF-7对所合成的目标化合物进行体外抗增殖活性筛选。结果与结论合成了9个未见文献报道的4-二苯基亚甲基色满类化合物,其结构经1H-NMR和ESI-MS谱确证。9个目标化合物均能抑制MCF-7细胞增殖。其中,化合物3a~3f对MCF-7细胞的体外抗增殖活性略优于化合物3g~3i。In order to discover novel selective estrogen receptor antagonists,based on the structures of clinical drug tamoxifen and its analogues with the triphenylethylene scaffold,a novel series of 4-(diphenyl-methylene)chroman derivatives with symmetrical structures were designed by the principle of bioisosterism,and nine target compounds(3 a-3 i)were synthesized.All the target compounds were characterized by~1H-NMR and ESI-MS.All the target compounds were evaluated for anticancer activity against the human breast cancer cell line MCF-7 in vitro using the MTT colorimetric assay.The results of biological activity evaluation showed that all the nine target compounds exhibited anti-proliferative activity against MCF-7.Among them,compounds 3 a-3 f have slightly better anti-proliferative activity than compounds 3g-3i.

关 键 词：色满类化合物 三苯乙烯骨架 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]