Pharmacophore-based 3D QSAR studies on a series of high affinity 5-HT(1A) 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. (C) 2010 Elsevier Masson SAS. All rights reserved.

National Council for Scientific and Technological Development (CNPq, Conselho Nacional de Pesquisa e Desenvolvimento)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The State of Sao Paulo Research Foundation (FAPESP, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Foundation for the Coordination of Higher Education and Graduate Training (CAPES, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior), Brazil