表皮生长因子受体酪氨酸激酶抑制剂的药效团研究

Pharmacophore Analysis of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors

根据一系列表皮生长因子受体酪氨酸激酶抑制剂的三维定量构效关系研究 ,得到了该类抑制剂的药效团 ,研究结果与Novartis的药效团模型相当类似 .药效团包括一个氢键受体 ,一个氢键给体 ,一个疏水区和一个带有氯或溴原子的苯环 .该药效团对于研究表皮生长因子受体酪氨酸激酶抑制剂结构与活性的关系具有重要的意义 .

A three-dimensional pharmacophore of epidermal growth factor receptor tyrosine kinase inhibitors was obtained based upon 3D-QSAR of a series of these inhibitors. The result was accordant with the pharmacophore model given by the scientists at Novartis. The pharmacophore included a hydrogen bond receptor, a hydrogen bond donor, a hydrophobic area and a phenyl ring with a chlorine or a bromine atom. This pharmacophore is very useful for clarifying the structure-activity relationships of EGFR tyrosine kinase inhibitors. Some lead compounds may be acquired through dime-dimensional database searching.