芳酰基类蛋白酪氨酸激酶抑制剂的合成及其活性研究  

Synthesis and protein tyrosine kinases inhibitory activity of aroyl derivatives

作　　者：汤玉兰[1] 唐林[2] 张首国[2] 彭涛[2] 温晓雪[2] 王刚[2] 刘曙晨[2] 王林[1,2] 

机构地区：[1]安徽医科大学,合肥230032 [2]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《国际药学研究杂志》2016年第3期471-475,共5页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金资助项目(81273431;81072531;21102176)

摘　　要：目的以Ex-Rad为先导化合物,设计并合成具有蛋白酪氨酸激酶(PTK)抑制活性的芳酰基类化合物。方法分别以1-[(4-氟苯基)氨基甲酰基]环丙烷羧酸、1-苯基咪唑烷-2-酮为原料合成中间体3a^3d,将中间体与羧酸通过酰氯法合成目标化合物T1~T7。用酶联免疫吸附法(ELISA)测定PTK抑制活性,计算抑制率,筛选出具有抑制PTK活性的化合物。结果合成芳酰基类新化合物7个,结构经~1H NMR确证。活性初筛发现化合物T_2、T_6的抑制活性强于先导化合物。结论合成方法简单,原料价廉易得。ELISA法测定结果表明T_2、T_6的PTK的抑制活性较强。Objective Using Ex-Rad as a lead compound to design and synthesize aroyl derivatives with protein tyrosine kinases（PTK）inhibitiory activity. Methods 1-[（4-Fluorophenyl）amioncarbonyl]cyclopropanecarboxylic acid,and 2-oxo-1-phenylimidazolidine were used as raw materials to synthesize intermediates 3a-3d,respectively. The target compounds T_1-T_7 were synthesized by chloroformylation reaction with 3a-3d. Enzyme-linked immunosorbent assay（ELISA）was used and inhibitory rate was calculated to screen out the compounds with PTK inhibitory activity. Results Seven new compounds containing aroyl groups were synthesized and their structures were confirmed by^1 H NMR. The evaluation of the seven compounds demonstrated that PTK inhibitory activity of T_2 and T_6were stronger than that of the lead compound. Conclusion The synthetic method is simple,and the materials are cheap and readily available. T_2 and T_6show strong PTK inhibitory activity by ELISA.

关 键 词：设计合成 芳酰基 蛋白酪氨酸激酶抑制剂 

分 类 号：R914.5[医药卫生—药物化学]