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使用Catalyst软件中的HipHop模块分别产生了AT1受体拮抗剂和ETA受体拮抗剂的三维药效团模型。AT1受体拮抗剂最优药效团模型(Hypo-AT1-7)和ETA受体拮抗剂最优药效团模型(Hypo-ETA-1)均经过仔细的验证。两种药效团含有5个药效团特征[氢键受体(A)、脂肪族疏水(Z)、阴离子基团(N)、芳环(R)及芳环疏水(Y)],这5个特征是受体结合力的决定性因素。双重AT1和ETA受体拮抗剂可以分别与药效团模型Hypo-AT1-7和Hypo-ETA-1叠合。通过比较叠合最优模型Hypo-AT1-7和Hypo-ETA-1,发现两种模型不仅总结了两种拮抗剂的必要结构特征,并具有共同之处。这个研究结果将作为一个有效的工具用于设计和研究新型AT1和ETA双重受体拮抗剂及其结构关系。
Using the HipHop module in the Catalyst software, three-dimensional pharmacophore models of AT1 receptor antagonists and ETA receptor antagonists were generated, respectively. The best pharmacophore model of AT1 receptor antagonist (Hypo-AT1-7) and the best pharmacophore model of ETA receptor antagonist (Hypo-ETA-1) were carefully examined. The two pharmacophores contain five pharmacophore features [hydrogen bond acceptor (A), aliphatic hydrophobic (Z), anionic group (N), aromatic ring (R) and aromatic ring hydrophobic Five characteristics are the decisive factors of receptor binding. Dual AT1 and ETA receptor antagonists can be superimposed on the pharmacophore models Hypo-AT1-7 and Hypo-ETA-1, respectively. By comparing the optimal models Hypo-AT1-7 and Hypo-ETA-1, we found that the two models not only sum up the essential structural features of the two antagonists, but also have similarities. The results of this study will serve as an effective tool for designing and studying new AT1 and ETA dual receptor antagonists and their structural relationships.