关键词: 激酶, 酪氨酸酶, 抑制剂, 定量构效关系, 柔性结构, 原子, 受体, 模型, 药物, 设计

A set of pyrimidine derivatives, tyrosine kinase inhibitors were investigated by using flexible atom receptor model. 3D-QSAR models were built with high correlation coefficients. The prediction results of these models on the biological activity of compounds in the test set show that they have high predictability. The flexible atom receptor model also gives the pesudo receptor model, which indicates possible interactions between the receptor and the ligands. The possible interactions include two hydrogen bonds, one hydrophobic interaction and one sulfur-aromatic interaction, which is highly accordant with the Novartis pharmacophore model.

Key words: KINASE, TYROSINASE, INHIBITOR, QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP, FLEXIBLE STRUCTURE, ATOM, ACCEPTOR, MODELS, DRUGS, DESIGN