摘要
以4-氯-6,7-二甲氧基喹唑啉、8-溴辛酸乙酯及溴代正丁烷等为原料,根据喹唑啉类化合物药效结构关系,对N-(3-氯-4-烷氧苯基)喹唑啉-4-胺类化合物(ARRY-334543)进行了结构修饰,合成了具有抗肿瘤细胞活性的酪氨酸激酶抑制剂(Ⅷa^c、Ⅸa和Ⅸb)。采用NMR和MS对抑制剂的结构进行了表征,并对其进行了抗肿瘤细胞活性测试。得到的化合物Ⅸa和Ⅸb均对MCF-7、BGC-823、A549、DU145和H1975细胞有一定的抗肿瘤活性,其中,活性最好的是化合物Ⅸa,其对MCF-7细胞的半数抑制浓度(GI50)为0.37μmol/L。
A series of tyrosine kinase inhibitors with antitumor activity were synthesized from 4-chloro-6,7-dimethoxy quinazoline,ethyl 8-bromooctanoate,n-butylbromide and other materials by the structural modification of N-（3-chloro-4-alkoxyphenyl） quinazolin-4-amine（ARRY-334543） based on the structure-activity relationship of the quinazoline derivatives. These compounds were characterized by NMR and MS. Subsequently,their antitumor activity tests were conducted. The results showed that although both compound Ⅸa and Ⅸb posed antitumor activity to MCF-7,BGC-823,A549,DU145 and H1975 cells,compound IXa showed better antitumor activity to MCF-7 than compound Ⅸ b,and the50% concentration inhibition（GI50） of compound IXa was 0. 37 μmol/L.
作者
宗豪强
姚志艺
ZONG Hao-qiang YAO Zhi-yi(College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai 210032, China)
出处
《精细化工》
EI
CAS
CSCD
北大核心
2017年第7期814-820,833,共8页
Fine Chemicals
基金
国家自然科学基金项目(2117220)~~
