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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 |
2002-5-6
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pubmed:abstractText |
A series of novel, selective TNF-alpha converting enzyme inhibitors based on 4-hydroxy and 5-hydroxy pipecolate hydroxamic acid scaffolds is described. The potency and selectivity of TACE inhibition is dramatically influenced by the nature of the sulfonamide group which interacts with the S1' site of the enzyme. Substituted 4-benzyloxybenzenesulfonamides exhibit excellent TACE potency with >100x selectivity over inhibition of matrix metalloprotease-1 (MMP-1). Alkyl substituents on the ortho position of the benzyl ether moiety give the most potent inhibition of TNF-alpha release in LPS-treated human whole blood.
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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 |
0960-894X
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pubmed:author |
pubmed-author:AxtMatt ZMZ,
pubmed-author:BarberiaJohn TJT,
pubmed-author:CartyThomas JTJ,
pubmed-author:DanleyDennis EDE,
pubmed-author:GeogheganKieran FKF,
pubmed-author:HalimNadia SNS,
pubmed-author:HothLise RLR,
pubmed-author:KamathAjith VAV,
pubmed-author:LairdEllen RER,
pubmed-author:LetavicMichael AMA,
pubmed-author:Lopresti-MorrowLori LLL,
pubmed-author:McClureKim FKF,
pubmed-author:MitchellPeter GPG,
pubmed-author:NatarajanVijayalakshmiV,
pubmed-author:NoeMark CMC,
pubmed-author:PanditJayvardhanJ,
pubmed-author:ReevesLisaL,
pubmed-author:SchulteGayle KGK,
pubmed-author:SnowSheri LSL,
pubmed-author:SweeneyFrancis JFJ,
pubmed-author:TanDouglas HDH,
pubmed-author:YuChul HCH
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1387-90
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11992783-ADAM Proteins,
pubmed-meshheading:11992783-Crystallography, X-Ray,
pubmed-meshheading:11992783-Drug Design,
pubmed-meshheading:11992783-Enzyme Inhibitors,
pubmed-meshheading:11992783-Humans,
pubmed-meshheading:11992783-Kinetics,
pubmed-meshheading:11992783-Metalloendopeptidases,
pubmed-meshheading:11992783-Models, Molecular,
pubmed-meshheading:11992783-Molecular Conformation,
pubmed-meshheading:11992783-Pipecolic Acids,
pubmed-meshheading:11992783-Structure-Activity Relationship,
pubmed-meshheading:11992783-Sulfonamides
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pubmed:year |
2002
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pubmed:articleTitle |
Synthesis and biological activity of selective pipecolic acid-based TNF-alpha converting enzyme (TACE) inhibitors.
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pubmed:affiliation |
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. michael_a_letavic@groton.pfizer.com
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pubmed:publicationType |
Journal Article
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