Pharmacophore-based 3D QSAR studies on a series of high affinity 5-HT1A receptor ligands.
5-HT(1A) receptor antagonists have been employed to treat depression, but the lack of structural information on this receptor hampers the design of specific and selective ligands. In this study, we have performed CoMFA studies on a training set of arylpiperazines (high affinity 5-HT(1A) receptor ligands) and to produce an effective alignment of the data set, a pharmacophore model was produced using Galahad. A statistically significant model was obtained, indicating a good internal consistency and predictive ability for untested compounds. The information gathered from our receptor-independent pharmacophore hypothesis is in good agreement with results from independent studies using different approaches. Therefore, this work provides important insights on the chemical and structural basis involved in the molecular recognition of these compounds.
Departamento de Química, Universidade Federal da Paraíba, Cidade Universitária, 58051-970, João Pessoa - PB, Brazil.
Karen C
KC
Weber
Lívia B
LB
Salum
Káthia M
KM
Honório
Adriano D
AD
Andricopulo
Albérico B F
AB
da Silva
D008024:Ligands; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism
D008024:Ligands; D044282:Receptor, Serotonin, 5-HT1A