Linked Life Data

16202587

Source:http://linkedlifedata.com/resource/pubmed/id/16202587

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2005-10-19
pubmed:abstractText
N-(4-Methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea (AR-A014418), a highly selective inhibitor of glycogen synthase kinase-3beta (GSK-3beta), was radiolabelled with carbon-11 (half-life=20.4min) for cerebral positron emission tomography (PET) studies. Reaction of desmethyl AR-A014418 with [(11)C]CH(3)I produced [(11)C]AR-A014418 in 17% decay-corrected radiochemical yield, based on [(11)C]CO(2), with 3230mCi/micromol specific activity after a 30min synthesis time. The desmethyl precursor of AR-A014418 was synthesized in 23% yield by a novel one-pot reaction of 2-amino-5-nitrothiazole with in situ generated TMS-protected 4-hydroxybenzylisocyanate, following deprotection with acid. Ex vivo biodistribution studies were conducted after [(11)C]AR-A014418 was administered via tail vein injection into Sprague-Dawley rats. Very low levels of radioactivity were found in all brain regions (0.08% injected dose/gram of tissue) at 5 and 30min post-injection, uncorrected for vascular compartment. Considering the extremely poor brain penetration of [(11)C]AR-A014418 this compound cannot be used to study GSK-3beta in cerebral PET studies. Furthermore, the specific pharmacological mechanism(s) of antidepressant-like activity attributed to AR-A014418 should be investigated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0960-894X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5270-3
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Synthesis and ex vivo evaluation of carbon-11 labelled N-(4-methoxybenzyl)-N'-(5-nitro-1,3-thiazol-2-yl)urea ([11C]AR-A014418): a radiolabelled glycogen synthase kinase-3beta specific inhibitor for PET studies.
pubmed:affiliation
PET Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, Ont., Canada M5T-1R8. neil.vasdev@camhpet.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't