6,7-二甲氧基-4-芳胺基喹唑啉衍生物的合成与活性筛选  

Synthesis and Bioactivity of 6,7-Dimethoxy-Quinazoline-4-Arylamine Derivatives

作　　者：许传莲[1] 郭宗香[1] 章砚东[2] 赵辅昆[1] 许根俊[1] 俞永平[2] 

机构地区：[1]浙江理工大学生命科学学院,杭州310018 [2]浙江大学药学院,杭州310031

出　　处：《中国药学杂志》2007年第22期1748-1752,共5页Chinese Pharmaceutical Journal

基　　金：浙江省科技厅重点项目资助(2004C21019)

摘　　要：目的合成6,7-二甲氧基-4-芳胺基喹唑啉衍生物及其抗肿瘤活性筛选。方法以2-氨基-4,5-二甲氧基苯甲酸和醋酸甲脒为原料,合成了10个4位芳胺取代的6,7-二甲氧基喹唑啉衍生物,利用酶联免疫吸附分析法(ELISA)PTK-101试剂盒并对化合物进行活性筛选。结果合成的化合物经IR,1H-NMR,MS结构表征。初步的生物活性测试表明,这类化合物对表皮生长因子受体(EGFR)酪氨酸激酶有明显的抑制活性。其苯环4′位的取代基变化对活性具有显著影响。结论6,7-二甲氧基-4-芳胺基喹唑啉衍生物可能会在治疗肿瘤特别是非小细胞肺癌方面发挥更大。OBJECTIVE To study the synthesis of 4-arylamino substituted 6,7-dimethoxylqui-nazoline and its derivatives.METHOD 4-Arylamino substituted 6,7-dimethoxylquinzoline were synthesized by 2-amion-4,5-dimethoxylbenzoicacid and formamidine acetate.RESULT The structures of the compounds were confirmed by IR, ^1H-NMR MS and melting point. The bioassay results indicated that some of the compounds show certain inhibition against EGFR-TK. In addition,varying substituents on 4-arylaniline in the compormd leadsed to different bioactivities.CONCLUSION 4-Arylamino substituted 6,7-dimethoxylquinazoline and the its derivatives may develop a new drug against non small cell lung cane-er.

关 键 词：喹唑啉衍生物 EGFR抑制剂 生物活性 

分 类 号：R914.5[医药卫生—药物化学]