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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2008-7-25
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pubmed:abstractText |
A series of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes were prepared and evaluated for affinities at dopamine, serotonin, and norepinephrine transporters using competitive radioligand binding assays. The 2beta-[3'-(substituted benzyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes (3a-h) showed high binding affinities for the dopamine transporter (DAT). The IC(50) values ranged from 5.9 to 22nM. On the other hand, the 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes (4a-h), with IC(50) values ranging from 65 to 173nM, were approximately 3- to 25-fold less potent than the corresponding 2beta-[3'-(substituted benzyl)isoxazol]tropanes. All tested compounds were selective for the DAT relative to the norepinephrine transporter (NET) and serotonin transporter (5-HTT). 3Beta-(4-Methylphenyl)-2beta-[3'-(4-fluorobenzyl)isoxazol-5-yl]tropane (3b) with IC(50) of 5.9nM at the DAT and K(i)s of 454 and 113nM at the NET and 5-HTT, respectively, was the most potent and DAT-selective analog. Molecular modeling studies suggested that the rigid conformation of the isoxazole side chain in 4a-h might play an important role on their low DAT binding affinities.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-10029980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-10195128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-11255924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-12210554,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-12723940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-14612141,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-14711303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-15351386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-1552510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-16584128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-17017960,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-17067572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-1719677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-17602602,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-1826041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-1895292,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-2529365,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-2820058,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-4747968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-7480530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-7658431,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-8176704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-8411004,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-8709106,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-9083474,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-9126740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18556210-9836615
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1464-3391
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6682-8
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pubmed:dateRevised |
2010-12-3
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pubmed:meshHeading |
pubmed-meshheading:18556210-Animals,
pubmed-meshheading:18556210-Binding, Competitive,
pubmed-meshheading:18556210-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:18556210-Humans,
pubmed-meshheading:18556210-Inhibitory Concentration 50,
pubmed-meshheading:18556210-Models, Molecular,
pubmed-meshheading:18556210-Norepinephrine Plasma Membrane Transport Proteins,
pubmed-meshheading:18556210-Plasma Membrane Neurotransmitter Transport Proteins,
pubmed-meshheading:18556210-Radioligand Assay,
pubmed-meshheading:18556210-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:18556210-Structure-Activity Relationship,
pubmed-meshheading:18556210-Tropanes
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pubmed:year |
2008
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pubmed:articleTitle |
Synthesis and monoamine transporter binding properties of 2beta-[3'-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3'-methyl-4'-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes.
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pubmed:affiliation |
Organic and Medicinal Chemistry, Research Triangle Institute, PO Box 12194, Research Triangle Park, NC 27709-2194, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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