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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2008-6-10
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pubmed:abstractText |
We herein disclose a novel series of 4-aminopyrimidine-5-carbaldehyde oximes that are potent and selective inhibitors of both EGFR and ErbB-2 tyrosine kinases, with IC(50) values in the nanomolar range. Structure-activity relationship (SAR) studies elucidated a critical role for the 4-amino and C-6 arylamino moieties. The X-ray co-crystal structure of EGFR with 37 was determined and validated our design rationale.
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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 |
Jun
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:AbadMarta CMC,
pubmed-author:AdamsMaryM,
pubmed-author:BeckAmanda KAK,
pubmed-author:ConnollyPeter JPJ,
pubmed-author:EmanuelStuart LSL,
pubmed-author:Fuentes-PesqueraAngel RAR,
pubmed-author:GreenbergerLee MLM,
pubmed-author:GruningerRobert HRH,
pubmed-author:HughesTerry VTV,
pubmed-author:MiddletonSteven ASA,
pubmed-author:Moreno-MazzaSandraS,
pubmed-author:NeeperMichael PMP,
pubmed-author:PandeyNiranjanN,
pubmed-author:SearleLily LeeLL,
pubmed-author:SpringerBarry ABA,
pubmed-author:StrubleGeoffrey TGT,
pubmed-author:XuGuozhangG
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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 |
3495-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18508264-Animals,
pubmed-meshheading:18508264-Antineoplastic Agents,
pubmed-meshheading:18508264-Binding Sites,
pubmed-meshheading:18508264-Cell Line, Tumor,
pubmed-meshheading:18508264-Cell Proliferation,
pubmed-meshheading:18508264-Crystallography, X-Ray,
pubmed-meshheading:18508264-Dose-Response Relationship, Drug,
pubmed-meshheading:18508264-Drug Design,
pubmed-meshheading:18508264-Drug Screening Assays, Antitumor,
pubmed-meshheading:18508264-Humans,
pubmed-meshheading:18508264-Hydrogen Bonding,
pubmed-meshheading:18508264-Inhibitory Concentration 50,
pubmed-meshheading:18508264-Models, Molecular,
pubmed-meshheading:18508264-Molecular Structure,
pubmed-meshheading:18508264-Oximes,
pubmed-meshheading:18508264-Pyrimidines,
pubmed-meshheading:18508264-Rats,
pubmed-meshheading:18508264-Rats, Sprague-Dawley,
pubmed-meshheading:18508264-Receptor, Epidermal Growth Factor,
pubmed-meshheading:18508264-Receptor, erbB-2,
pubmed-meshheading:18508264-Stereoisomerism,
pubmed-meshheading:18508264-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Discovery of novel 4-amino-6-arylaminopyrimidine-5-carbaldehyde oximes as dual inhibitors of EGFR and ErbB-2 protein tyrosine kinases.
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pubmed:affiliation |
Johnson & Johnson Pharmaceutical Research & Development, Medicinal Chemistry, 8 Clarke Drive, Cranbury, NJ 08512, USA. gxu4@prdus.jnj.com
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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