一类酪氨酸激酶抑制剂的合成及抗肿瘤活性

Synthesis and Antitumor Activity Research of A Kind of Tyrosine Kinase Inhibitor

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。采用NMR和MS对化合物的结构进行了表征，并对其进行了抗肿瘤细胞活性测试。得到的化合物IX a ~ b均对MCF-7、BGC-823、A549、DU145和H1975细胞有一定的抗肿瘤活性，活性最好的是化合物IX a，其半数抑制浓度（GI50）为0.37μmol/L。

Abstract:

A series of tyrosine kinase inhibitors which showed antitumor activity were synthesized with 4-chloro-6,7-dimethoxy quinazoline, ethyl 8-bromooctanoate, n-butylbromide and other raw materials, the structuralmodification of N-(3-chloro-4-alkoxyphenyl)quinazolin-4-amine (ARRY-334543) was based on structure-activity relationship of quinazoline derivatives.Structure of these compounds were characterized by NMR and MS , and anti-tumor activity test of the compounds were conducted. Both target compound IX a ~ b posed antitumor activity to MCF-7, BGC-823, A549, DU145 and H1975 cells. Particularly, compound IX a showed the best antitumor activity which 50% concentration inhibition (GI50) is 0.37 μmol/L.