3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (σ1) receptor.
Bioorg Med Chem Lett
; 23(6): 1707-11, 2013 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-23414839
ABSTRACT
Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure-activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (σ1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q(2)) regression value of 0.6, and a non-cross validated r(2) of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of a test set with an r(2) >0.7. We also describe here the docking of the PCU-derived compounds into a homology model of the sigma-1 (σ1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [(3)H]pentazocine binding assay an oxa-PCU, NGP1-01 (IC50=1.78µM) and its phenethyl derivative (IC50=1.54µM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(σ1) receptor.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores sigma
/
Relação Quantitativa Estrutura-Atividade
/
Aminas
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article