Linked Life Data

9357521

Source:http://linkedlifedata.com/resource/pubmed/id/9357521

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1997-12-11
pubmed:abstractText
The synthesis and binding affinity at cloned h5-HT1D, h5-HT1D, and h5-HT1A receptors of 3-[3-(N,N-dimethylamino)propyl]-4-hydroxy- N-[4-(pyridin-4-yl)phenyl]benzamide (2, GR-55562) and four O-methylated analogs are described. The functional activity of these compounds was determined at the h5-HT1B receptor using a [35S]GTP gamma S binding assay. The four analogs have been prepared in order to evaluate the influence of the alkylamino side chain conformation on binding and intrinsic activity. Whereas 2 and its derivatives display a similar binding affinity profile, major differences arise from analysis of the intrinsic activity data at h5-HT1B receptors. The O-methylated analog of 2, 3-[3-(N,N-dimethylamino)propyl]-4-methoxy- N-[4-(pyridin-4-yl)phenyl]benzamide (3a), and the (1Z)-3-(N,N-dimethylamino)prop-1-enyl derivative (3c) act as neutral and potent antagonists (in a similar way to 2), while the 3-(N,N-dimethylamino)-prop-1-ynyl (3b) and (1E)-3-(N,N-dimethylamino)prop-1-enyl (3d) analogs display nonnegligible agonist activity. Molecular modeling studies show that, when the common triaryl portions of the molecules are overlapped, the partial agonists and the neutral antagonists differ by a near-orthogonal orientation of the NH+ projection to the hydrogen-bond receptor site.
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
24
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3542-50
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Differentiation between partial agonists and neutral 5-HT1B antagonists by chemical modulation of 3-[3-(N,N-dimethylamino)propyl]-4-hydroxy- N-[4-(pyridin-4-yl)phenyl]benzamide (GR-55562).
pubmed:affiliation
Cellular and Molecular Biology Department, Centre de Recherche Pierre FABRE, Castres, France.
pubmed:publicationType
Journal Article