Scientific Article
previous document  unige:10571  next document
add to browser collection
Title

Modeling of beta-adrenoceptors based on molecular electrostatic potential studies of agonists and antagonists

Authors
el Tayar, Nabil
Van de Waterbeemd, Hans
Testa, Bernard
Published in Journal of Medicinal Chemistry. 1988, vol. 31, no. 11, p. 2072-2081
Abstract The molecular electrostatic potential (MEP) of 32 beta-adrenoceptor ligands, mainly antagonists, was calculated by the STO-3G ab initio quantum mechanical method. The MEP of phenylethanolamines (PEAs) features a negative minimum in the meta region (designated M1) which is topographically equivalent to a minimum (designated M2) found in the vicinity of the aromatic ring in all (aryloxy)propanolamines (AOPAs). In these compounds, a second negative zone located beyond the meta position and designated M3 is found in all beta 1-selective antagonists and in some nonselective and beta 2-selective antagonists. The beta 1-selective antagonists feature in the para position an additional zone which is positive (P4) in the full antagonists and negative (M4) in the antagonists displaying intrinsic sympathomimetic activity (ISA). The MEP-based pharmacophoric models of PEAs, AOPAs, and oxime ethers show common elements and lead to a proposed general model for beta-adrenoceptor ligands.
Keywords Adrenergic beta-Agonists/*pharmacologyAdrenergic beta-Antagonists/*pharmacologyModels, MolecularReceptors, Adrenergic, betaStructure-Activity Relationship
Stable URL http://archive-ouverte.unige.ch/unige:10571
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://pubs.acs.org/doi/pdf/10.1021/jm00119a004
Identifiers
PMID: 2903243
126 hits and 0 download since 2010-08-06
Update
Export document
Format :
Citation style :