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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2008-4-15
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pubmed:abstractText |
The synthesis and structure-activity relationships (SAR) of p38 alpha MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound 2x as a potent and selective inhibitor of p38 alpha MAP kinase with excellent cellular potency toward the inhibition of TNFalpha production. Compound 2x was highly efficacious in vivo in inhibiting TNFalpha production in an acute murine model of TNFalpha production. X-ray co-crystallography of a pyrazolo-pyrimidine analog 2b bound to unphosphorylated p38 alpha is also disclosed.
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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 |
Apr
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:BarrishJoel CJC,
pubmed-author:DasJagabandhuJ,
pubmed-author:DoddJohn HJH,
pubmed-author:DoweykoArthur MAM,
pubmed-author:GilloolyKathleenK,
pubmed-author:KieferSusan ESE,
pubmed-author:KishKevinK,
pubmed-author:LeftherisKaterinaK,
pubmed-author:McIntyreKim WKW,
pubmed-author:McKinnonMurrayM,
pubmed-author:MoquinRobert VRV,
pubmed-author:PittSidneyS,
pubmed-author:SackJohn SJS,
pubmed-author:SchievenGary LGL,
pubmed-author:ShenDing RenDR,
pubmed-author:ZhangHongjianH,
pubmed-author:ZhangRosemaryR
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2652-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18359226-Crystallography, X-Ray,
pubmed-meshheading:18359226-Humans,
pubmed-meshheading:18359226-Models, Molecular,
pubmed-meshheading:18359226-Molecular Structure,
pubmed-meshheading:18359226-Protein Kinase Inhibitors,
pubmed-meshheading:18359226-Pyrazoles,
pubmed-meshheading:18359226-Pyrimidines,
pubmed-meshheading:18359226-Structure-Activity Relationship,
pubmed-meshheading:18359226-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2008
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pubmed:articleTitle |
Pyrazolo-pyrimidines: a novel heterocyclic scaffold for potent and selective p38 alpha inhibitors.
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pubmed:affiliation |
Bristol-Myers Squibb Research and Development, PO Box 4000, Princeton, NJ 08543-4000, USA. jagabandhu.das@bms.com
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pubmed:publicationType |
Journal Article
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