科研之友
微信
新浪微博
Facebook
分享链接
摘要
A three dimensional-quantitative structure activity relationship (3D-QSAR) study was performed on a series of CETP inhibitors N,N-disubstituted trifluoro-3-amino-2-propanol derivatives using VolSurf descriptors and the comparative molecular field analysis (CoMFA) method. Good results were obtained and the training set was predictable for the test set. VolSurf descriptor analysis showed that suitable hydrophilicity, more hydrogen bond donors and less acceptor were favorable to activity. To some extent, high molecular weight, a smooth surface and high non-globularity were also beneficial to activity. High hydrophobicity and tin imbalance between the center of mass and the barycentre of its hydrophobic regions decreased the activity. The result of CoMFA demonstrated that the activity was influenced more by steric effect than electrostatic effect. At the phenoxy meta position in the N-phenyl substituent, groups that have a large volume and strong positive electricity increase the activity. At the meta position of the N-benzyl substituent, groups that have a large Volume and suitable electronegativity were beneficial to activity. At the para position of the benzyl group, a large steric effect was detrimental to activity. VolSurf descriptors provided the integral property information of the molecules and CoMFA gave information on substituents. Both methods complemented each other, which can provide assistance to the design of new compounds belonging to this class of inhibitors.
- 出版日期2008-12
- 单位浙江大学; 浙江大学宁波理工学院
