Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
Bioorg Med Chem Lett. 2010 Nov 15;20(22):6764-72. doi: 10.1016/j.bmcl.2010.08.131. Epub 2010 Sep 24.
3D-QSAR and docking studies were performed on a series of pyrazolo[4,3-h]quinazoline-3-carboxamides as CDK2/CyA inhibitors. The CoMFA and CoMSIA models using 54 molecules in the training set, gave r(cv)(2) values of 0.644 and 0.507, r(2) values of 0.959 and 0.951, respectively. 3D contour maps generated from the two models were applied to identify features important for the activity and better understand the interaction between the inhibitors and the receptor. Molecular docking was employed to explore the binding mode between these compounds and the receptor, as well as help understanding the structure-activity relationship revealed by CoMFA and CoMSIA. The results provide a useful guideline for the rational design of novel CDKs inhibitors.
采用 CoMFA 和 CoMSIA 方法对一系列作为 CDK2/CyA 抑制剂的吡唑并[4,3-h]喹唑啉-3-甲酰胺类化合物进行了 3D-QSAR 和对接研究。在训练集中使用 54 个分子，CoMFA 和 CoMSIA 模型的 r(cv)(2) 值分别为 0.644 和 0.507，r(2) 值分别为 0.959 和 0.951。从这两个模型生成的 3D 等高线图可用于确定对活性很重要的特征，从而更好地了解抑制剂与受体之间的相互作用。采用分子对接研究了这些化合物与受体之间的结合模式，以帮助理解 CoMFA 和 CoMSIA 揭示的构效关系。研究结果为合理设计新型 CDK 抑制剂提供了有用的指导。
