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rdf:type |
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lifeskim:mentions |
umls-concept:C0003209,
umls-concept:C0038477,
umls-concept:C0205177,
umls-concept:C0205314,
umls-concept:C0205531,
umls-concept:C0220781,
umls-concept:C0226896,
umls-concept:C0243077,
umls-concept:C0442027,
umls-concept:C0679622,
umls-concept:C1527415,
umls-concept:C1883254
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pubmed:issue |
15
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pubmed:dateCreated |
2004-6-30
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pubmed:abstractText |
A series of 2-amino-3-cyano-4-alkyl-6-(2-hydroxyphenyl)pyridine derivatives was synthesized and evaluated as I kappaB kinase beta (IKK-beta) inhibitors. Modification of a novel IKK-beta inhibitor 1 (IKK-beta IC(50)=1500 nM, Cell IC(50)=8000 nM) at the 4-phenyl ring and 6-phenol group on the pyridine core ring resulted in a marked increased in biological activities. An optimized compound, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile, exhibited excellent in vitro profiles (IKK-beta IC(50)=8.5 nM, Cell IC(50)=60 nM) and a strong oral efficacy in in vivo anti-inflammatory assays (significant effects at 1mg/kg, po in arachidonic acid-induced ear edema model in mice).
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CHUK protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chuk protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/IKBKE protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbkb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ikbke protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:BaconKevin BKB,
pubmed-author:FuchikamiKinjiK,
pubmed-author:FukushimaKeikoK,
pubmed-author:KomuraHiroshiH,
pubmed-author:KoriyamaYujiY,
pubmed-author:LowingerTimothy BTB,
pubmed-author:MasudaTsutomuT,
pubmed-author:MurataToshikiT,
pubmed-author:NunamiNorikoN,
pubmed-author:SakakibaraSachikoS,
pubmed-author:SatoHirokiH,
pubmed-author:ShimadaMitsuyukiM,
pubmed-author:ShintaniTakuyaT,
pubmed-author:WatanabeAkihikoA,
pubmed-author:YamauchiMegumiM,
pubmed-author:YoshinoTakashiT,
pubmed-author:ZiegelbauerKarl BKB
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pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4019-22
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15225718-Animals,
pubmed-meshheading:15225718-Anti-Inflammatory Agents,
pubmed-meshheading:15225718-Disease Models, Animal,
pubmed-meshheading:15225718-Edema,
pubmed-meshheading:15225718-Humans,
pubmed-meshheading:15225718-I-kappa B Kinase,
pubmed-meshheading:15225718-Kinetics,
pubmed-meshheading:15225718-Mice,
pubmed-meshheading:15225718-Models, Molecular,
pubmed-meshheading:15225718-Molecular Structure,
pubmed-meshheading:15225718-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15225718-Pyridines,
pubmed-meshheading:15225718-Recombinant Proteins,
pubmed-meshheading:15225718-Structure-Activity Relationship
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pubmed:year |
2004
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pubmed:articleTitle |
Synthesis and structure-activity relationships of novel IKK-beta inhibitors. Part 3: Orally active anti-inflammatory agents.
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pubmed:affiliation |
Department of Chemistry, Research Center Kyoto, Bayer Yakuhin Ltd., Kizu, Soraku, Kyoto 619-0216, Japan. muratato@kcn.ne.jp
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pubmed:publicationType |
Journal Article
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