Weber Karen C, Honório Káthia M, Andricopulo Adriano D, Da Silva Albérico B F
Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
Med Chem. 2008 Jul;4(4):328-35. doi: 10.2174/157340608784872325.
5-HT(1A) receptor plays an important role in the delayed onset of antidepressant action of a class of selective serotonin reuptake inhibitors. Moreover, 5-HT(1A) receptor levels have been shown to be altered in patients suffering from major depression. In this work, hologram quantitative structure-activity relationship (HQSAR) studies were performed on a series of arylpiperazine compounds presenting affinity to the 5-HT(1A) receptor. The models were constructed with a training set of 70 compounds. The most significant HQSAR model (q(2) = 0.81, r(2) = 0.96) was generated using atoms, bonds, connections, chirality, and donor and acceptor as fragment distinction, with fragment size of 6-9. Predictions for an external test set containing 20 compounds are in good agreement with experimental results showing the robustness of the model. Additionally, useful information can be obtained from the 2D contribution maps.
5-羟色胺（1A）受体在一类选择性5-羟色胺再摄取抑制剂的抗抑郁作用延迟起效过程中发挥重要作用。此外，在重度抑郁症患者中，5-羟色胺（1A）受体水平已显示发生改变。在本研究中，对一系列对5-羟色胺（1A）受体具有亲和力的芳基哌嗪化合物进行了全息定量构效关系（HQSAR）研究。模型构建采用了70种化合物的训练集。使用原子、键、连接、手性以及供体和受体作为片段区分，片段大小为6 - 9，生成了最显著的HQSAR模型（交叉验证系数q(2) = 0.81，决定系数r(2) = 0.96）。对包含20种化合物的外部测试集的预测与实验结果高度吻合，表明该模型具有稳健性。此外，可从二维贡献图中获得有用信息。
