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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。
Starting from 4-chloro-6,7-dimethoxyquinazoline, 8-bromooctanoic acid ethyl ester and n-butyl bromide, according to the pharmacodynamic structure of quinazolines, N- (3- Chloro-4-alkoxyphenyl) quinazolin-4-amine (ARRY-334543) was synthesized and the tyrosine kinase inhibitors with anti-tumor cell activity (Ⅷa ~ c, Ⅸa and Ⅸb ). The structure of the inhibitor was characterized by NMR and MS, and its anti-tumor cell activity was tested. The obtained compounds IXa and IXb all have certain antitumor activities against MCF-7, BGC-823, A549, DU145 and H1975 cells, wherein the most active compounds are compounds IXa which have a half inhibitory concentration ( GI50) was 0.37 μmol / L.