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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2010-6-3
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pubmed:abstractText |
Structural modification of a virtual screening hit led to the identification of a new series of 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols which are potent and selective inhibitors of the norepinephrine transporter over both the serotonin and dopamine transporters. One representative compound S-17b (WYE-103231) had low nanomolar hNET potency (IC(50) = 1.2 nM) and excellent selectivity for hNET over hSERT (>1600-fold) and hDAT (>600-fold). S-17b additionally had a good pharmacokinetic profile and demonstrated oral efficacy in rat models of ovariectomized-induced thermoregulatory dysfunction and morphine dependent flush as well as the hot plate and spinal nerve ligation (SNL) models of acute and neuropathic pain.
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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 |
Jun
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:AdedoyinAdedayoA,
pubmed-author:AlfinitoPeter DPD,
pubmed-author:BrayJenifer AJA,
pubmed-author:CosmiScottS,
pubmed-author:DeecherDarlene CDC,
pubmed-author:FensomeAndrewA,
pubmed-author:HarrisonJimJ,
pubmed-author:LeventhalLizaL,
pubmed-author:MannCharlesC,
pubmed-author:McComasCasey CCC,
pubmed-author:O'NeillDavid JDJ,
pubmed-author:SpanglerTaylor BTB,
pubmed-author:SullivanNicole RNR,
pubmed-author:TrybulskiEugene JEJ,
pubmed-author:UvegesAlbert JAJ,
pubmed-author:WhitesideGarth TGT,
pubmed-author:ZhangPuwenP
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pubmed:issnType |
Electronic
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pubmed:day |
10
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4511-21
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pubmed:meshHeading |
pubmed-meshheading:20462211-Animals,
pubmed-meshheading:20462211-Cell Line,
pubmed-meshheading:20462211-Cyclic S-Oxides,
pubmed-meshheading:20462211-Drug Discovery,
pubmed-meshheading:20462211-Female,
pubmed-meshheading:20462211-Humans,
pubmed-meshheading:20462211-Male,
pubmed-meshheading:20462211-Neurotransmitter Uptake Inhibitors,
pubmed-meshheading:20462211-Norepinephrine,
pubmed-meshheading:20462211-Rats,
pubmed-meshheading:20462211-Structure-Activity Relationship,
pubmed-meshheading:20462211-Thiadiazoles
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pubmed:year |
2010
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pubmed:articleTitle |
Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231).
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pubmed:affiliation |
Chemical Sciences, Pfizer Global Research & Development, 500 Arcola Road, Collegeville, Pennsylvania 19426, USA. david.oneill@pfizer.com
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pubmed:publicationType |
Journal Article
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