Two-dimensional QSAR studies on arylpiperazines as high-affinity 5-HT(1A) receptor ligands


Autoria(s): WEBER, Karen C.; HONORIO, Kathia M.; ANDRICOPULO, Adriano Defini; SILVA, Alberico B. F. Da
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2008

Resumo

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.

Identificador

MEDICINAL CHEMISTRY, v.4, n.4, p.328-335, 2008

1573-4064

http://producao.usp.br/handle/BDPI/30020

10.2174/157340608784872325

http://dx.doi.org/10.2174/157340608784872325

Idioma(s)

eng

Publicador

BENTHAM SCIENCE PUBL LTD

Relação

Medicinal Chemistry

Direitos

restrictedAccess

Copyright BENTHAM SCIENCE PUBL LTD

Palavras-Chave #HQSAR #arylpiperazines #5-HT(1A) receptor #SSRIs #drug design #SEROTONIN REUPTAKE INHIBITORS #PLACEBO-CONTROLLED TRIAL #QUANTITATIVE STRUCTURE #DOUBLE-BLIND #MUTANT MICE #DUAL-ACTION #DERIVATIVES #PINDOLOL #ANTIDEPRESSANTS #TRANSPORTER #Chemistry, Medicinal
Tipo

article

original article

publishedVersion