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Two-Dimensional QSAR Studies on Arylpiperazines as High-Affinity 5-HT1A Receptor Ligands

[ Vol. 4 , Issue. 4 ]

Author(s):

Karen C. Weber, Kathia M. Honorio, Adriano D. Andricopulo and Alberico B. F. Da Silva   Pages 328 - 335 ( 8 )

Abstract:


5-HT1A receptor plays an important role in the delayed onset of antidepressant action of a class of selective serotonin reuptake inhibitors. Moreover, 5-HT1A 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-HT1A receptor. The models were constructed with a training set of 70 compounds. The most significant HQSAR model (q2 = 0.81, r2 = 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.

Keywords:

HQSAR, arylpiperazines, 5-HT1A receptor, SSRIs, drug design

Affiliation:

Instituto de Quimica de Sao Carlos, Universidade de Sao Paulo, Av. Trabalhador Sao-Carlense, 400,13560-970, Sao Carlos, SP, Brazil.



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