具有抗组胺（H1）活性的一系列稠合噻吩并[2,3-d]嘧啶-4(3H)-酮的 CoMFA 和 CoMSIA 3D-QSAR 模型。

CoMFA and CoMSIA 3D QSAR models for a series of some condensed thieno[2,3-d]pyrimidin-4(3H)-ones with antihistaminic (H1) activity.

机构信息

Department of Pharmaceutical Chemistry, L.M. College of Pharmacy, Navrangpura, Gujarat, India.

出版信息

Med Chem. 2013 May;9(3):389-401. doi: 10.2174/1573406411309030010.

Abstract

Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies were carried out for a series of thienopyrimidines, novel Histamine H1 receptor antagonists. Various models were generated. The best predictive CoMFA model gave significant correlation coefficients (cross-validated r2 (q2) = 0.514, non-cross-validated r2 = 0.925), showing the influence of steric and electrostatic fields. Likewise, the best predictive CoMSIA model gave cross-validated r2 (q2) = 0.541, non-cross-validated r2 = 0.862, eliciting the influence of steric, electrostatic, hydrophobic and hydrogen bond acceptor fields. The generated models were externally validated and well correlated with calculated (predicted) and experimental inhibitory concentration (IC50) values, using test sets. The analysis of the contour maps of both CoMFA and CoMSIA models offer important structural insight for designing novel and more active Histamine H1 receptor antagonists prior to their synthesis.

摘要

对一系列噻吩并嘧啶类新型组胺 H1 受体拮抗剂进行了比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）研究。生成了各种模型。最佳预测 CoMFA 模型给出了显著的相关系数（交叉验证 r2（q2）= 0.514，非交叉验证 r2 = 0.925），表明了立体和静电场的影响。同样，最佳预测 CoMSIA 模型给出了交叉验证 r2（q2）= 0.541，非交叉验证 r2 = 0.862，表明了立体、静电、疏水和氢键接受场的影响。使用测试集对生成的模型进行了外部验证，并与计算（预测）和实验抑制浓度（IC50）值进行了很好的相关性。CoMFA 和 CoMSIA 模型的等高线图分析为在合成之前设计新型和更有效的组胺 H1 受体拮抗剂提供了重要的结构见解。