Two-dimensional QSAR studies on arylpiperazines as high-affinity 5-HT(1A) receptor ligands.
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.
Weber
Karen C
KC
Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
Honório
Káthia M
KM
Andricopulo
Adriano D
AD
Da Silva
Albérico B F
AB
D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D044263:Receptors, Serotonin, 5-HT1 / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists
D008024:Ligands; D010879:Piperazines; D044263:Receptors, Serotonin, 5-HT1; D058829:Serotonin 5-HT1 Receptor Antagonists; D000077489:Piperazine