厄洛替尼衍生物的合成及抗肿瘤活性研究  

Synthesis and antitumor activity of erlotinib derivatives

作　　者：赵智伟 田思琪 杜宇 王春光 陈晓杰[1,2] 郝雪琴[1,2] Zhao Zhiwei;Tian Siqi;Du Yu;Wang Chunguang;Chen Xiaojie;Hao Xueqin(School of Basic Medical Sciences,The First Affiliated Hospital,Henan University of Science and Technology,Luoyang 471003,China;Henan Provincial Key Laboratory of Tumor Epigenetics,Henan University of Science and Technology,Luoyang 471003,China;Henan Wanliu Biotechnology Co.,Ltd.,Luoyang 471000,China)

机构地区：[1]河南科技大学基础医学院,第一附属医院,河南洛阳471003 [2]河南科技大学河南省肿瘤表观遗传重点实验室,河南洛阳471003 [3]河南湾流生物科技有限公司,河南洛阳471000

出　　处：《河南师范大学学报（自然科学版）》2023年第2期102-108,共7页Journal of Henan Normal University(Natural Science Edition)

基　　金：河南省自然科学基金(182300410370);河南省科技攻关项目(222102310362).

摘　　要：以2-氨基-4,5-双(2-甲氧基乙氧基)苯甲酸乙酯盐酸盐为起始原料,经过环合、氯化、取代得到厄洛替尼,然后在其端基炔结构上通过点击化学反应与苄基叠氮反应得到4种1,2,3-三氮唑类化合物,其中化合物5a对肺癌细胞HCC827及其吉非替尼耐药细胞的HCC827GR具有一定的抑制效果,优于厄洛替尼,并且引起HCC827细胞阻滞在G2/M期,引起HCC827GR细胞在G0/G1期阻滞.Erlotinib was obtained from 2-amino-4,5-bis(2-methoxyethoxy)ethyl benzoate hydrochloride by cyclization,chlorination and substitution.Then four erlotinib derivatives were designed and synthesized from erlotinib with azido compounds via click reaction.Their anti-tumor activity were evaluated against HCC827 and HCC827GR tumor cells.Compound 5a showed a certain inhibitory effect on non-small cell lung cancer HCC827 cell and corresponding gefitinib-resistant cell HCC827GR cell,which was superior to erlotinib.Compound 5a also can block HCC827 cells in G2/M phase and HCC827GR cells in G0/G1 phase.

关 键 词：厄洛替尼 1 2 3-三氮唑 抗肿瘤药物 细胞周期 

分 类 号：R914.5[医药卫生—药物化学]