基于构效关系的非肽类血管紧张素Ⅱ受体阻滞剂分子设计

Molecular design of non-peptide angiotensin II receptor blockers based on quantitative structure-activity relationship

目的:研究非肽类血管紧张素Ⅱ(AngⅡ)受体阻滞剂定量构效关系及分子设计。方法:应用半经验量子化学方法和误差反向传播人工神经网络方法建立AngⅡ受体阻滞剂的定量构效关系(QSAR)模型,用该模型预测新设计的化合物的药效参数。结果:系统地计算了70个非肽类血管紧张素Ⅱ受体阻滞剂的18个量化参数,从中筛选出5个建立QSAR模型。随机挑选6个化合物作为验证集,剩余64个化合物作为学习集,验证结果表明:所建立的QSAR模型具有较高的精度。设计并预测了30个新化合物的药效参数,其中5个化合物的预测药效较好。结论:成功建立非肽类AngⅡ受体阻滞剂的QSAR模型,该模型为此类药物的结构改造和新药设计提供了参考意见和有效途径。

Objective：To investigate and the QSAR model molecular design of the non-peptide angiotensin Ⅱ （Ang Ⅱ） receptor blockers. Methods： A QSAR model of Ang Ⅱ receptor blockers was established based on the methods of Semi-empirical quantum chemistry and Back-Propagation network. The pharmacodynamic parameters of new compounds were mimicked with the established model. Results： 18 molecular quantum chemical parameters of 70 Ang Ⅱ receptor blockers have been calculated,5 were used to build the QSAR model 6 out of the 70 Ang Ⅱ receptor blockers were randomly selected as a validation set for the QSAR model. 64 out of the 70 Ang Ⅱ receptor blockers were used as a training set for the QSAR model. The error analysis showed the high precision of the QSAR model. The pharmacodynamic parameters of 30 new compounds were predicted using the QSAR model, of which 5 were disclosed to have better biological prognosis. Conclusion ： The QSAR model of non-peptide angiotensin Ⅱ receptor blockers can provide a rationale in the structural modification and new drug design of such non-peptide angiotensin II receptor blockers.