Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
|
pubmed:dateCreated |
1997-5-1
|
pubmed:abstractText |
In search of an alpha2-antagonist/5-HT uptake inhibitor as a potential new class of antidepressant with a more rapid onset of action, compound 3 was prepared and observed to possess high affinity for the alpha2-receptor (K(i) = 6.71 nM) and the 5-HT uptake site (20.6 nM). A series of tertiary amine analogs of 3 were synthesized and assayed for their affinity at both the alpha2-receptor and the 5-HT uptake site. The structure-activity relationship reveals that a variety of structural modifications to the arylethyl fragment are possible with retention of this dual activity. On the tetralin portion, 5-OMe substitution and the (R) stereochemistry at C-1 are optimal with alternate substitutions producing compounds retaining high affinity for the alpha2-receptor but lacking affinity for the 5-HT uptake site. Data for several rigidified 5-O-alkyl analogs suggests that the favored orientation of the oxygen lone pairs may be away from the 6-position of the tetralin.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-2 Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Methylamines,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
0022-2623
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
28
|
pubmed:volume |
40
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
1049-62
|
pubmed:dateRevised |
2010-11-18
|
pubmed:meshHeading |
pubmed-meshheading:9089327-Adrenergic alpha-2 Receptor Antagonists,
pubmed-meshheading:9089327-Adrenergic alpha-Antagonists,
pubmed-meshheading:9089327-Animals,
pubmed-meshheading:9089327-Cerebral Cortex,
pubmed-meshheading:9089327-Magnetic Resonance Spectroscopy,
pubmed-meshheading:9089327-Methylamines,
pubmed-meshheading:9089327-Rats,
pubmed-meshheading:9089327-Serotonin Uptake Inhibitors,
pubmed-meshheading:9089327-Stereoisomerism,
pubmed-meshheading:9089327-Structure-Activity Relationship
|
pubmed:year |
1997
|
pubmed:articleTitle |
Structure-activity studies for a novel series of N-(arylethyl)-N-(1,2,3,4-tetrahydronaphthalen-1-ylmethyl)-N-methylamine s possessing dual 5-HT uptake inhibiting and alpha2-antagonistic activities.
|
pubmed:affiliation |
Neuroscience Research, Department 47C, Pharmaceutical Products Division, Abbott Park, Illinois 60064, USA.
|
pubmed:publicationType |
Journal Article
|