Linked Life Data

8893836

Source:http://linkedlifedata.com/resource/pubmed/id/8893836

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1996-12-10
pubmed:abstractText
A series of secondary and tertiary N-alkyl derivatives of (R)-2-amino-5-fluorotetralin have been prepared. The affinities of the compounds for [3H]raclopride-labeled cloned human dopamine (DA) D2 and D3 receptors as well as [3H]-8-OH-DPAT-labeled rat hippocampal 5-HT1A receptors were determined. In order to selectively determine affinities for the high-affinity agonist binding site at DA D2 receptors, the agonist [3H]quinpirole was used. The intrinsic activities of the compounds at DA D2 and D3 receptors were evaluated in a [35S]GTP gamma S binding assay. The novel compounds were characterized as dopaminergic antagonists or inverse agonists. The antagonist (R)-2-(butylpropylamino)-5-fluorotetralin (16) bound with high affinity (Ki = 4.4 nM) to the DA D3 receptor and was the most D3-selective compound (10-fold). (R)-2-[[4-(8-Aza-7, 9-dioxospiro[4.5]decan-8-yl)butyl]propylamino]-5-fluorote tralin (18) bound with very high affinity to both DA D3 and 5-HT1A receptors (Ki = 0.2 nM) and was also characterized as a dopaminergic antagonist. (R)-2-(Benzylpropylamino)-5-fluorotetralin (10) behaved as an inverse agonist at both DA D2 and D3 receptors. It decreased the basal [35S]GTP gamma S binding and potently inhibited the DA-stimulated [35S]GTP gamma S binding. It is apparent that the intrinsic activity of a 2-aminotetralin derivative may be modified by varying the N-alkyl substituents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4421-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Novel (R)-2-amino-5-fluorotetralins: dopaminergic antagonists and inverse agonists.
pubmed:affiliation
Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, Uppsala University, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't