芳酰基类蛋白酪氨酸激酶抑制剂的合成及其活性研究

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T2、T6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T2、T6的PTK的抑制活性较强。

Synthesis and protein tyrosine kinases inhibitory activity of aroyl derivatives

Objective Using Ex-Rad as a lead compound to design and synthesize aroyl derivatives with protein tyrosine ki?nases(PTK)inhibitiory activity. Methods 1-(4-Fluorophenyl)amioncarbonyl]cyclopropanecarboxylic acid,and 2-oxo-1-phenyl-imidazolidine were used as raw materials to synthesize intermediates 3a-3d,respectively. The target compounds T1-T7 were synthe?sized by chloroformylation reaction with 3a-3d. Enzyme-linked immunosorbent assay(ELISA)was used and inhibitory rate was calcu?lated to screen out the compounds with PTK inhibitory activity. Results Seven new compounds containing aroyl groups were synthe?sized and their structures were confirmed by 1H NMR. The evaluation of the seven compounds demonstrated that PTK inhibitory activi?ty of T2 and T6 were stronger than that of the lead compound. Conclusion The synthetic method is simple,and the materials are cheap and readily available. T2 and T6 show strong PTK inhibitory activity by ELISA.