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采用分子全息定量构效关系(HQSAR)方法,研究了21个HIV-1逆转录酶抑制剂苯基氨基吡啶派生物(Phenylaminopyridine,PAP)类化合物的构效关系;探讨了碎片区分参数、分子碎片大小和分子全息长度对模型质量的影响;建立了一组以16个化合物为训练集的最优模型,其交叉验证相关系数q~2为0.801,非交叉验证相关系数r~2为0.963,标准偏差为0.363;对5个化合物构成的测试集进行了预测,其相关系数r_(pred)~2为0.92,表明该模型具有良好的预测能力。最后,通过HQSAR模型色码图对PAP类化合物的活性起重要作用的片段与结构进行了讨论,并根据HQASR最佳模型图设计出了20种PAP派生物类化合物,这些化合物理论上均具有较好的抗HIV-1活性,为PAP派生物类化合物的进一步合成提供理论指导。
The structure-activity relationship of 21 compounds of phenylaminopyridine (PAP), a HIV-1 reverse transcriptase inhibitor, was investigated by using molecular holographic quantitative structure-activity relationship (HQSAR) method. The effects of fragmentation parameters, molecular fragmentation Size and molecular holographic length on the model quality. A set of optimal models with 16 compounds as the training set was established. The correlation coefficient of cross-validation was 0.801, the correlation coefficient of non-cross-validation was 0.963. The standard The deviation was 0.363. The test set composed of five compounds was predicted with a correlation coefficient r_ (pred) ~ 2 of 0.92, indicating that the model has good predictive ability. Finally, the fragments and structures that play an important role in the activity of PAP compounds are discussed by the HQSAR model color-coded map. According to the HQASR best model diagram, 20 PAP derivatives are designed, and these compounds are theoretically more efficient The good anti-HIV-1 activity provides theoretical guidance for the further synthesis of PAP derivatives.