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基于定量构效关系和分子对接研究理论,以34个噻吩并嘧啶酮类磷酸二酯酶7(PDE7)抑制剂为研究对象,采用比较分子相似性指数法(Co MSIA)和GOLD分子对接法研究其特征结构信息以及与靶标的作用机制。结果表明,所建立Co MSIA模型的预测能力较强(Q2=0.53,R2ncv=0.96,R2pre=0.89),结合分子对接结果还发现,抑制剂与PDE7间的作用力以氢键作用力和π-π堆积作用为主;大体积的亲水性氢键供体R1取代基、亲水性R2取代基有利于化合物活性的增强,且哌啶环上有益于结合氢键的受体基团。所得模型和信息为后续新型PDE7抑制剂的设计开发提供理论指导。
Based on the quantitative structure-activity relationship and the molecular docking theory, 34 thienopyrimidinones phosphodiesterase 7 (PDE7) inhibitors were used as the research object, and comparative molecular similarity index (Co MSIA) and GOLD docking method Its structural information and the mechanism of action with the target. The results showed that the established Co MSIA model had strong predictive ability (Q2 = 0.53, R2ncv = 0.96, R2pre = 0.89). The results of molecular docking showed that the interaction between PDE7 and inhibitor was hydrogen bond force and π- π stacking effect. The large hydrophilic donor hydrogen substituent R1, the hydrophilic R2 substituent is beneficial to the enhancement of the activity of the compound, and the acceptor group on the piperidine ring is conducive to hydrogen bonding. The obtained models and information provide theoretical guidance for the design and development of new PDE7 inhibitors.