Linked Life Data

6980283

Source:http://linkedlifedata.com/resource/pubmed/id/6980283

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1982-9-24
pubmed:abstractText
Resolution of the unique dopamine receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (1) was achieved by a stereospecific multistep conversion of the readily separated enantiomers of its O,O,N-trimethylated precursor 2. The absolute stereochemistry of the antipodes of 2-MeI was determined by single-crystal X-ray diffractometric analysis, thus permitting assignment of the configuration of stereospecifically related 1, as well as that of the synthetic intermediates. High-performance liquid chromatography of diastereoisomeric derivatives was utilized to determine the enantiomeric excess of the R (greater than 97%) and S (greater than 89%) isomers of 1. Examination of the isomers in several in vitro and in vivo tests for both central and peripheral dopaminergic activity revealed that activity resided almost exclusively in the R isomer. The results suggest that the properly oriented 1-phenyl substituent of 1 is important for dopamine-like activity; it may contribute to receptor binding by interaction with a chirally defined accessory site. Configurational and conformational requirements for receptor binding of 1 are considered in relationship to previously described dopaminergic agents. These studies, in accord with previous suggestions, indicate that (R)-1 interacts with dopamine receptors in a conformation in which the catecholic hydroxyls and basic nitrogen are at least nearly maximally separated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
697-703
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1982
pubmed:articleTitle
Absolute stereochemistry and dopaminergic activity of enantiomers of 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine.
pubmed:publicationType
Journal Article, In Vitro