Artículos de revistas
Two- and three-dimensional quantitative structure-activity relationships studies on a series of liver x receptor ligands
Fecha
2008Registro en:
Open Medicinal Chemistry Journal, Bussum : Bentham Open, v. 2, p. 87-96, 2008
1874-1045
Autor
Honório, Káthia Maria
Salum, Lívia B.
Garratt, Richard Charles
Polikarpov, Igor
Andricopulo, Adriano Defini
Institución
Resumen
Liver X receptor (LXR) is an attractive drug target for the development of novel therapeutic agents for the treatment of dyslipidaemia and cholestasis. In the present work, comparative molecular field analysis (CoMFA) and hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of potent LXR ligands. Significant correlation coefficients (CoMFA, 'r POT. 2' = 0.98 and 'q POT. 2' = 0.69; HQSAR, 'r POT. 2' = 0.99 and 'q POT. 2' = 0.85) were obtained, indicating the potential of the models for untested compounds. The models were then used to predict the potency of an external test set, and the predicted values obtained from the 2D and 3D models were in good agreement with the experimental results. The final QSAR models, along with the information obtained from 3D steric and electrostatic contour maps and 2D contribution maps should be useful for the design of novel LXR ligands having improved potency.