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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2001-10-9
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pubmed:abstractText |
Directed screening of a carboxylic acid-containing combinatorial library led to the discovery of potent inhibitors of the integrin VLA-4. Subsequent optimization by solid-phase synthesis afforded a series of sulfonylated dipeptide inhibitors with structural components that when combined in a single hybrid molecule gave a sub-nanomolar inhibitor as a lead for medicinal chemistry. Preliminary metabolic studies led to the discovery of substituted biphenyl derivatives with low picomolar activities. SAR and pharmacokinetic characterization of this series are presented.
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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 |
Oct
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:ChangL LLL,
pubmed-author:CollettiAA,
pubmed-author:DuretteP LPL,
pubmed-author:EggerL ALA,
pubmed-author:FanJ SJS,
pubmed-author:Fenyk-MelodyJJ,
pubmed-author:HagmannW KWK,
pubmed-author:KameneckaTT,
pubmed-author:KevinN JNJ,
pubmed-author:KidambiUU,
pubmed-author:KimPP,
pubmed-author:KopkaI EIE,
pubmed-author:LanzaTT,
pubmed-author:LevorseDD,
pubmed-author:LyonsKK,
pubmed-author:MICC,
pubmed-author:MacCossMM,
pubmed-author:MagriotisP APA,
pubmed-author:McCauleyEE,
pubmed-author:MillsS GSG,
pubmed-author:MumfordR ARA,
pubmed-author:OwensKK,
pubmed-author:SchmidtJ AJA,
pubmed-author:StearnsRR,
pubmed-author:TefferaJJ,
pubmed-author:TongSS,
pubmed-author:Van RiperGG,
pubmed-author:VincentSS,
pubmed-author:WilsonJJ,
pubmed-author:YanoOO,
pubmed-author:YoungDD,
pubmed-author:de LaszloS ESE
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pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2709-13
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pubmed:dateRevised |
2003-11-14
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pubmed:meshHeading |
pubmed-meshheading:11591507-Animals,
pubmed-meshheading:11591507-Biological Availability,
pubmed-meshheading:11591507-Dipeptides,
pubmed-meshheading:11591507-Dogs,
pubmed-meshheading:11591507-Integrin alpha4beta1,
pubmed-meshheading:11591507-Integrins,
pubmed-meshheading:11591507-Macaca mulatta,
pubmed-meshheading:11591507-Metabolic Clearance Rate,
pubmed-meshheading:11591507-Rats,
pubmed-meshheading:11591507-Receptors, Lymphocyte Homing,
pubmed-meshheading:11591507-Structure-Activity Relationship,
pubmed-meshheading:11591507-Sulfonic Acids
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pubmed:year |
2001
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pubmed:articleTitle |
The discovery of sulfonylated dipeptides as potent VLA-4 antagonists.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. william_hagmann@merck.com
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pubmed:publicationType |
Journal Article
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