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rdf:type |
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lifeskim:mentions |
umls-concept:C0205531,
umls-concept:C0220781,
umls-concept:C0226896,
umls-concept:C0243077,
umls-concept:C0442027,
umls-concept:C0935763,
umls-concept:C1120843,
umls-concept:C1366876,
umls-concept:C1527415,
umls-concept:C1707689,
umls-concept:C1883254
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pubmed:issue |
2
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pubmed:dateCreated |
2002-12-16
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pubmed:abstractText |
The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC(50)=10nM) and good oral exposure in rats (F=68%, AUCn PO=0.58 microM h).
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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 |
Jan
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:CameronPatricia MPM,
pubmed-author:DohertyJames BJB,
pubmed-author:HopCornelis E C ACE,
pubmed-author:LiuLupingL,
pubmed-author:NicholsElizabeth AEA,
pubmed-author:O'KeefeStephen JSJ,
pubmed-author:O'NeillEdward AEA,
pubmed-author:PatelSangita BSB,
pubmed-author:PivnichnyJames VJV,
pubmed-author:ScapinGiovannaG,
pubmed-author:SchmatzDennis MDM,
pubmed-author:SchwartzCheryl DCD,
pubmed-author:SinghSureshS,
pubmed-author:StelmachJohn EJE,
pubmed-author:StraussJohn RJR,
pubmed-author:ThompsonChris MCM,
pubmed-author:WangZhenZ,
pubmed-author:ZallerDennis MDM
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
277-80
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12482439-Animals,
pubmed-meshheading:12482439-Area Under Curve,
pubmed-meshheading:12482439-Biological Availability,
pubmed-meshheading:12482439-Drug Design,
pubmed-meshheading:12482439-Enzyme Inhibitors,
pubmed-meshheading:12482439-Microsomes, Liver,
pubmed-meshheading:12482439-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12482439-Models, Molecular,
pubmed-meshheading:12482439-Molecular Conformation,
pubmed-meshheading:12482439-Monocytes,
pubmed-meshheading:12482439-Quinazolines,
pubmed-meshheading:12482439-Rats,
pubmed-meshheading:12482439-Structure-Activity Relationship,
pubmed-meshheading:12482439-Tumor Necrosis Factor-alpha,
pubmed-meshheading:12482439-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2003
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pubmed:articleTitle |
Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. john_stelmach@merck.com
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pubmed:publicationType |
Journal Article,
In Vitro
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