7-(4-烃氧基苯基)-4-(4-芳基哌嗪-1-基)-5,6,7,8-四氢苯并[4,5]噻吩并[2,3-d]嘧啶类化合物的合成与抗肿瘤活性研究  

Synthesis and antiproliferative activity of 7-(4- hydrocarbonoxyphenyl)-4-(4-arylpiperazin-1-yl)-5,6,7,8- tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives

作　　者：尹秀娥 焦娣 孙冰[2] 麻卿卿 冯健 刘晓平[2] 胡春[2] YIN Xiue;JIAO Di;SUN Bing;MA Qingqing;FENG Jian;LIU Xiaoping;HU Chun(Liaoning Grand Nuokang Biopharmaceutical Co.,Ltd.,Shenyang 110171,China;Key Laboratary of Structure-Based Drug Design and Discovery(Shenyang Pharmaceutical University),Ministry of Education,Shenyang 110016,China)

机构地区：[1]辽宁远大诺康生物制药有限公司,辽宁沈阳110171 [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：《沈阳药科大学学报》2020年第2期118-125,共8页Journal of Shenyang Pharmaceutical University

摘　　要：目的设计合成一系列7-(4-烃氧基苯基)-4-(4-芳基哌嗪-1-基)-5,6,7,8-四氢苯并[4,5]噻吩并[2,3-d]嘧啶类化合物并进行抗肿瘤活性研究。方法以4-(4-羟基苯基)环己酮、氰乙酰胺、单质硫作为起始原料,通过Gewald反应、改进后的Niementowski喹唑啉缩合反应、三氯氧磷氯代反应、亲核取代反应、脱乙基反应及Williamson反应得到相应的目标化合物,采用MTT法测定目标化合物体外抑制人类肺癌细胞株A549增殖的活性,并初步探究其构效关系。结果与结论目标化合物8a、8c、8f和8k在10μmol·L-1浓度下对肿瘤细胞的抑制率达到30%以上,有进一步研究的价值。Objective To explore the synthesis and the biological activity of 7-(4-hydrocarbonoxyphenyl)-4-(4-arylpiperazin-1-yl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives.based on the influenza virus ribonucleoprotein complex,and the preliminary action mechanism of 3-aryl-quinazolin-4(3H)-one derivatives.Methods Using 4-(4-hydroxyphenyl)cyclohexanone,cyanoacetamide and sulfur as starting materials,the target compounds were synthesized via Gewald reaction,modified Niementowski quinazoline condensation,chlorination,nucleophilic substitution,deethylation and Williamson reactions,and the biological activity were tested.Results and Conclusions Fourteen 7-(4-hydrocarbonoxyphenyl)-4-(4-arylpiperazin-1-yl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives were synthesized and characterized by IR,1H-NMR and MS.The antiproliferative activity of the target compounds were evaluated against human pulmonary carcinoma cell line A549 by MTT assay in vitro.Preliminary results showed that tumor cell inhibitory ratios of the target compounds 8 a,8 c,8 f and 8 k were more than 30% at 10μmol·L-1 concentration.These compounds were worthy of further study.

关 键 词：杂环化合物 四氢苯并[4 5]噻吩并[2 3-d]嘧啶 合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]