Linked Life Data

2522990

Source:http://linkedlifedata.com/resource/pubmed/id/2522990

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1989-5-15
pubmed:abstractText
In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use of experimental (NMR spectroscopic studies) and theoretical (MMP2, AM1, and MNDO calculations) methods. Topographical characteristics were studied by use of molecular graphics. Results from the MMP2 calculations agree with those from the AM1 calculations and the NMR spectroscopic study--1 seems to preferentially adopt chair conformations with a pseudoequatorial C6 substituent. The MNDO calculations, however, produced results that deviate considerably from those of the other theoretical methods. Most likely, pharmacophore conformations of (S)-1 do not present volumes that are part of the DA D2 receptor essential volume. Therefore, it appears that the energy penalty paid by the pharmacophore conformations is responsible for the dopaminergic inactivity of (S)-1. The inactivity of (R)-1 may be due to high energies of pharmacophore conformations and/or to steric factors since these conformations produce large excess volumes that may be part of the DA D2 receptor essential volume. The model used in the present report--a flexible pharmacophore combined with a partial receptor-excluded volume--might be used in the design of new DA D2 receptor agonists.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
765-74
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Topography and conformational preferences of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6- ylamin e. A rationale for the dopaminergic inactivity.
pubmed:affiliation
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, University of Uppsala, Sweden.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't