Scientific Article
previous document  unige:10576  next document
add to browser collection
Title

Binding of arylpiperazines, (aryloxy)propanolamines, and tetrahydropyridylindoles to the 5-HT1A receptor: contribution of the molecular lipophilicity potential to three-dimensional quantitative structure-affinity relationship models

Authors
Gaillard, Patrick
Testa, Bernard
Schambel, P.
Published in Journal of Medicinal Chemistry. 1996, vol. 39, no. 1, p. 126-134
Abstract A set of 280 5-HT1A receptor ligands were selected from available literature data according to predefined criteria and subjected to three-dimensional quantitative structure-affinity relationship analysis using comparative molecular field analysis. No model was obtained for serotonin analogues (19 compounds) and aminotetralins (60 compounds), despite a variety of alignment hypotheses being tried. In contrast, the steric, electrostatic, and lipophilicity fields alone and in combination yielded informative models for arylpiperazines (101 training compounds and 12 test compounds), (aryloxy)propanolamines (30 training compounds and four test compounds), and tetrahydropyridylindoles (54 training compounds) taken separately (models A, B, and C). Arylpiperazines and (aryloxy)propanolamines were then combined successfully to yield reasonably good models for 131 compounds (model D). In a last step, the three chemical classes (185 compounds) were combined, again successfully (model E). This stepwise procedure not only ascertains self-consistency in alignments but it also allows statistical signals (i.e., favorable or unfavorable regions around molecules) to emerge which cannot exist in a single chemical class. The models so obtained reveal a number of interaction sites between ligands and the 5-HT1A receptor, and extend the information gathered from a model based on homology modeling.
Keywords Indoles/chemistry/*metabolismLigandsModels, MolecularMolecular ConformationMolecular StructurePiperazines/chemistry/*metabolismPropanolamines/chemistry/*metabolismReceptors, Serotonin/*metabolismReceptors, Serotonin, 5-HT1Serotonin/metabolismStructure-Activity RelationshipTetrahydronaphthalenes/chemistry/metabolism
Stable URL http://archive-ouverte.unige.ch/unige:10576
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://pubs.acs.org/doi/pdf/10.1021/jm950410b
Identifiers
PMID: 8568799
133 hits and 0 download since 2010-08-06
Update
Export document
Format :
Citation style :