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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-4-1
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pubmed:abstractText |
We report the design and discovery of a 2-aminobenzimidazole-based series of potent and highly selective p38alphainhibitors. The lead compound 1 had low-nanomolar activity in both ATP competitive enzyme binding and inhibition of TNFalpha release in macrophages. Compound 18 showed excellent pharmacokinetics properties and oral activity in the rat collagen induced arthritis model compared with other p38 reference compounds. A SAR strategy to address CyP3A4 liability is also described.
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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 |
0022-2623
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pubmed:author |
pubmed-author:AndersonBryan DBD,
pubmed-author:Blanco-UrgoitiJaimeJ,
pubmed-author:BonjouklianRosanneR,
pubmed-author:CampbellRobert MRM,
pubmed-author:GieraDeborah DDD,
pubmed-author:JohnsonLea MLM,
pubmed-author:López de UraldeBeatrizB,
pubmed-author:LeePaul APA,
pubmed-author:LoriteMaría JoséMJ,
pubmed-author:MagnusNicholasN,
pubmed-author:Martín CabrejasLuisa MLM,
pubmed-author:McCannDenis JDJ,
pubmed-author:NevillC RichardCRJr,
pubmed-author:NonyP APA,
pubmed-author:PleiteSehilaS,
pubmed-author:SánchezConcepciónC,
pubmed-author:SchultzRichard MRM,
pubmed-author:ShihChuanC,
pubmed-author:ViethMichalM,
pubmed-author:WangYongY,
pubmed-author:WolosJeffrey AJA,
pubmed-author:YorkJeremyJ,
pubmed-author:de DiosAlfonsoA,
pubmed-author:del PradoMiriamM
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
48
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2270-3
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15801819-Administration, Oral,
pubmed-meshheading:15801819-Animals,
pubmed-meshheading:15801819-Anti-Inflammatory Agents,
pubmed-meshheading:15801819-Arthritis, Experimental,
pubmed-meshheading:15801819-Benzimidazoles,
pubmed-meshheading:15801819-Binding Sites,
pubmed-meshheading:15801819-Biological Availability,
pubmed-meshheading:15801819-Collagen,
pubmed-meshheading:15801819-Crystallography, X-Ray,
pubmed-meshheading:15801819-Drug Design,
pubmed-meshheading:15801819-Humans,
pubmed-meshheading:15801819-Lipopolysaccharides,
pubmed-meshheading:15801819-Macrophages, Peritoneal,
pubmed-meshheading:15801819-Mice,
pubmed-meshheading:15801819-Mice, Inbred BALB C,
pubmed-meshheading:15801819-Mitogen-Activated Protein Kinase 14,
pubmed-meshheading:15801819-Models, Molecular,
pubmed-meshheading:15801819-Rats,
pubmed-meshheading:15801819-Tumor Necrosis Factor-alpha
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pubmed:year |
2005
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pubmed:articleTitle |
Design of potent and selective 2-aminobenzimidazole-based p38alpha MAP kinase inhibitors with excellent in vivo efficacy.
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pubmed:affiliation |
Eli Lilly and Co., Lilly S.A., Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain. a.de_dios@lilly.com
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pubmed:publicationType |
Journal Article
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