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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2011-5-2
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pubmed:abstractText |
A weak, UDP-competitive antagonist of the pyrimidinergic receptor P2RY(14) with a naphthoic acid core was identified through high-throughput screening. Optimization provided compounds with improved potency but poor pharmacokinetics. Acylglucuronidation was determined to be the major route of metabolism. Increasing the electron-withdrawing nature of the substituents markedly reduced glucuronidation and improved the pharmacokinetic profile. Additional optimization led to the identification of compound 38 which is an 8 nM UDP-competitive antagonist of P2Y(14) with a good pharmacokinetic profile.
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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 |
May
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:BelleyMichelM,
pubmed-author:BlackW CameronWC,
pubmed-author:DeschênesDenisD,
pubmed-author:FournierJean-FrançoisJF,
pubmed-author:GagnéSébastienS,
pubmed-author:GareauYvesY,
pubmed-author:GauthierJacques YvesJY,
pubmed-author:HénaultMartinM,
pubmed-author:HamelMartineM,
pubmed-author:HyjazieHudaH,
pubmed-author:KargmanStaciaS,
pubmed-author:KwaDD,
pubmed-author:LavalléeGenevièveG,
pubmed-author:LevesqueJean-FrançoisJF,
pubmed-author:LiLianhaiL,
pubmed-author:MamaneYaëlY,
pubmed-author:ManciniJosephJ,
pubmed-author:MorinNicolasN,
pubmed-author:MulrooneyErinE,
pubmed-author:RobichaudJoëlJ,
pubmed-author:ThérienMichelM,
pubmed-author:TranmerGeoffreyG,
pubmed-author:WangZhaoyinZ
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2836-9
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pubmed:meshHeading |
pubmed-meshheading:21507640-Animals,
pubmed-meshheading:21507640-Binding, Competitive,
pubmed-meshheading:21507640-Carboxylic Acids,
pubmed-meshheading:21507640-Mice,
pubmed-meshheading:21507640-Molecular Structure,
pubmed-meshheading:21507640-Naphthalenes,
pubmed-meshheading:21507640-Pan troglodytes,
pubmed-meshheading:21507640-Protein Binding,
pubmed-meshheading:21507640-Purinergic P2 Receptor Antagonists,
pubmed-meshheading:21507640-Receptors, Purinergic P2,
pubmed-meshheading:21507640-Structure-Activity Relationship,
pubmed-meshheading:21507640-Uridine Diphosphate
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pubmed:year |
2011
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pubmed:articleTitle |
The identification of 4,7-disubstituted naphthoic acid derivatives as UDP-competitive antagonists of P2Y14.
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pubmed:affiliation |
Merck Frosst Centre for Therapeutic Research, 16711 TransCanada Hwy, Kirkland, Quebec, Canada H9H 3L1.
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pubmed:publicationType |
Journal Article
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