用定量构效关系分析进行酪氨酸激酶抑制剂的结构类型衍化

THE LEAD GENERATION OF PROTEIN TYROSINE KINASE INHIBITORS BY QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS

用QSAR方法分析了取代的亚苄丙二腈类衍生物的定量构效关系,结果表明苯环上的两个或两个以上的羟基与侧链上可极化的共轭链的存在是酪氨酸激酶抑制剂的必要结构。与其它类型的抑制剂作构效分析,衍化出对这类酶有抑制作用的基本结构。

Analysis of the quantitative relationship between a series of substitutedbenzylidenemalononitriles and the inhibitory action on protein tyrosine Kinases were car-ried out using the Hansch- Fujita method. The results indicate that the presence of two orthree hydroxy groups attached to a phenyl ring, which connects an extended (trans form)conjugated chain, is essential to the inhibition. Compared with the structure of other kindsof inhibitors, a presumable basic structure for inhibiting the enzyme was generated.