酪氨酸蛋白激酶抑制剂的合成及生物活性

SYNTHESIS AND BIOLOGICAL ACTIVITY OF TYROSINE PROTEIN KINASE INHIBITORS

摘要: 设计并合成了四类共25个酪氨酸蛋白激酶(TPK)抑制剂。用ATP参入法测定了化合物1～10对HL-60白血病来源的TPK的抑制作用,有些化合物表现出明显的抑制活性。构效关系(SAR)表明,呈现抑制活性的必要结构或基团与文献报道的构效关系相一致。还尝试了酶联免疫吸附法(ELISA)测定化合物11～25对正常鼠脾来源的TPK的抑制作用,结果表明这种方法与ATP参入法所得的构效关系有很大的不同。

Abstract: Four classes of 25 tyrosine protein kinase (TPK) inhibitors were designed and synthesized. Compounds 1 ～ 10 were tested to inhibit TPK of HL-60 leukemia cell using ³²P-ATP method, and some of them exhibit evident inhibitory activities. Their structure-activity relationship is similar to that of TPK inhibitors reported in literatures. Compounds 11 ～ 25 were tested to inhibit TPK of normal rat spleen cell using ELISA method and their SAR is different from that using ³²P-ATP method.