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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
17
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pubmed:dateCreated |
2010-9-2
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pubmed:abstractText |
The p38 mitogen-activated protein kinase (MAPK) plays an important role in the production of proinflammatory cytokines, making it an attractive target for the treatment of various inflammatory diseases. A series of pyridazinopyridinone compounds were designed as novel p38 kinase inhibitors. A structure-activity investigation identified several compounds possessing excellent potency in both enzyme and human whole blood assays. Among them, compound 31 exhibited good pharmacokinetic properties and showed excellent selectivity against other related kinases. In addition, 31 demonstrated efficacy in a collagen-induced arthritis disease model in rats.
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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 |
Sep
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:DohertyElizabeth MEM,
pubmed-author:DyeII,
pubmed-author:HenkleBradleyB,
pubmed-author:HsiehFayeF,
pubmed-author:LeeMatthew RMR,
pubmed-author:McBrideHelen JHJ,
pubmed-author:PettusLipingL,
pubmed-author:PlantMatthew HMH,
pubmed-author:SarisChristiaan J MCJ,
pubmed-author:ShermanLisaL,
pubmed-author:TaskerAndrew SAS,
pubmed-author:WangHui-LingHL,
pubmed-author:WongLu MinLM,
pubmed-author:WurzRyan PRP
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pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6398-411
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pubmed:meshHeading |
pubmed-meshheading:20712346-Activating Transcription Factor 2,
pubmed-meshheading:20712346-Animals,
pubmed-meshheading:20712346-Antirheumatic Agents,
pubmed-meshheading:20712346-Arthritis, Experimental,
pubmed-meshheading:20712346-Binding Sites,
pubmed-meshheading:20712346-Collagen,
pubmed-meshheading:20712346-Female,
pubmed-meshheading:20712346-Humans,
pubmed-meshheading:20712346-Interleukin-8,
pubmed-meshheading:20712346-Lipopolysaccharides,
pubmed-meshheading:20712346-Male,
pubmed-meshheading:20712346-Models, Molecular,
pubmed-meshheading:20712346-Phosphorylation,
pubmed-meshheading:20712346-Pyridazines,
pubmed-meshheading:20712346-Pyridones,
pubmed-meshheading:20712346-Rats,
pubmed-meshheading:20712346-Rats, Inbred Lew,
pubmed-meshheading:20712346-Rats, Sprague-Dawley,
pubmed-meshheading:20712346-Structure-Activity Relationship,
pubmed-meshheading:20712346-Tumor Necrosis Factor-alpha,
pubmed-meshheading:20712346-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2010
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pubmed:articleTitle |
Discovery of pyridazinopyridinones as potent and selective p38 mitogen-activated protein kinase inhibitors.
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pubmed:affiliation |
Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Thousand Oaks, California 91320, USA. binw@amgen.com
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pubmed:publicationType |
Journal Article
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