Structural requirements of Na+-dependent antidopaminergic agents: Tropapride, Piquindone, Zetidoline, and Metoclopramide Comparison with Na+-independent ligands
- 1 March 1989
- journal article
- conference paper
- Published by Springer Nature in Journal of Computer-Aided Molecular Design
- Vol. 3 (1) , 39-53
- https://doi.org/10.1007/bf01590994
Abstract
Molecular graphic design coupled with PCILO and crystallographic results have been used to investigate the three-dimensional structure of Tropapride, Piquindone, Zetidoline, and Metoclopramide, four dopamine D-2 receptor antagonists showing Na+-dependent binding. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring and a carbonyl moiety, are similarly oriented in all the Na+-dependent drugs. Conversely, for Na+-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two Π-electron regions are systematically localized on the other side of the molecule: the first is a phenyl group while the second is a carbonyl function as in butyrophenones, a cyano group as in R48455, or a phenyl ring as in diphenylbutylpiperidines or tricyclics. The presence of a benzyl ring on this side in Tropapride might explain its weak extrapyramidal effects.Keywords
This publication has 32 references indexed in Scilit:
- Interactive flexible molecular fitting program to be integrated into computer-aided molecular modelling systemsJournal of Molecular Graphics, 1986
- Improving the flexible molecular fitting technique using distance matricesJournal of Computational Chemistry, 1986
- Crystal and molecular structure analysis of benzamide neuroleptics and analogs (VIII):endo- andexo-2,3-dimethoxy-N-[8-(phenylmethyl)-8-azabicyclo[3.2.1]oct-2-y1]-benzamide hydrochloride: C23H28N2O3·HClJournal of Chemical Crystallography, 1986
- Characterization of [3 H]zetidoline binding to rat striatal membranesJournal of Pharmacy and Pharmacology, 1985
- Structure Moléculaire De Neuroleptiques Derives Du 3‐Benzamido‐N‐Benzyl‐Nortropane. II. Maléate de N‐(8‐benzyl‐1αH, 5αH‐nortropan‐3 (β‐yl) 2,3,5‐triméthoxy benzamide: C24H30N2O4.C4H4O4Bulletin des Sociétés Chimiques Belges, 1984
- Molecular Structure Analyses of Neuroleptics Derived from 3‐Benzamido‐N‐Benzyl Nortropane. I. N‐(8‐Benzyl‐LαH, 5αH‐Nortropan‐3 β‐yl) 2‐Ethoxy, 3‐Methoxy Benzamide Hydrochloride: C24H30N2O3.HClBulletin des Sociétés Chimiques Belges, 1984
- Molecular Structure of Benzamide Neuroleptics V. Amino‐2, Methoxy‐4 N‐(α‐Methylphenylmethyl)‐8 Aza‐8 Bicyclo [3.2.1] Octyl‐3] Pyrimidine Carboxamide‐5 (Exo)Bulletin des Sociétés Chimiques Belges, 1984
- Molecular Structure of Benzamide Neuroleptics IV. Amino‐4, Bromo‐5, Methoxy‐2 π‐π (Chloro‐2 Phenylmethyl)‐8 Aza‐8 Bicyclo [ 3.2.1] Octyl‐3°] Benzamide (exo)Bulletin des Sociétés Chimiques Belges, 1984
- A theoretical conformational study of substituted o-anisamides as models of a class of dopamine antagonistsJournal of Pharmacy and Pharmacology, 1981
- A comparison between the conformation of dexclamol and the tricyclic and butyrophenone type dopamine antagonistsLife Sciences, 1978