组胺H_4受体配体的3D-QSAR模型分析

The 3D-QSAR model analysis of histamine H_4 receptor ligands.

组胺H4受体配体对于治疗哮喘、肿瘤、风湿性关节炎和瘙痒症等疾病具有一定作用.本文对一系列组胺H4受体配体进行了基于VolSurf参数的QSAR建模分析,得到了较好的结果(r2=0.86,q2=0.64),训练集模型对预测集具有良好的预测能力.参数分析表明分子体积与其活性成反比.具有适当的亲水性和较大的局部疏水体积的分子活性较高,分子内亲水区和疏水区具有合适的体积比也很关键,并且亲水区中心距离疏水区中心越远,分子的活性越高.氢键给体与受体的量对活性也有影响.分子平均极化率越高,配体的活性越低.

Histamine H4 receptor ligands are useful in the treatment of disease such as asthma,tumor,rheumatoid arthritis,and pruritus.The QSAR modeling analysis of a series of histamine H4 receptor ligands was given based on VolSurf parameters in this paper,nice result was got（r2=0.86,q2=0.64）,the model of the training set had a good predictive capability to the test set.The analysis of VolSurf descriptors demonstrated that the molecular volume is reversely proportional to its activity and molecules with proper hydrophilicity and voluminous local hydrophobicity have higher activity.Also,it is of great importance for an appropriate volume ratio of hydrophilic region to hydrophobic domain and the longer the distance between both centers of hydrophilic region and hydrophobic domain is,the more active is the molecule.Besides,the amount of hydrogen bond donors and acceptors could also weighes a lot and molecules with higher POL value have lower activity.