ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The conformational behaviour of metoclopramide, a neuroleptic benzamide, and model compounds was investigated byt 1 H-NMR spectroscopy. An intramolecular amide-methoxy H-bond is shown to exist in CDCl3-solution, but not in D2O-solution, independently of the length and protonation state of the basic side-chain. This H-bond creates a virtual cycle which may be a key feature for the binding of neuroleptic benzamides to the dopamine receptor. The conformational behaviour of the aminoethyl side-chain is shown to be markedly condition-dependent. For metoclopramide and its analogues in their protonated form, the gauche- and trans- rotamers have identical energies in D2O-as well as in CDCl3-solutins. For the non-protonated molecules, the trans-rotamer is favoured in D2O-solutin, while the gauche-rotamer is favoured in CDCl3-solution (ΔG°≃|0.5|kcal/mol in both cases). The side-chain conformation of neuroleptic benzamides is discussed in terms of receptor affinity.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19840670310
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