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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 |
2007-8-7
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pubmed:abstractText |
Pyrrolotriazine dual EGFR/HER2 kinase inhibitors with a 5-((4-aminopiperidin-1-yl)methyl) solubilizing group were found to be superior to analogs with previously reported C-5 solubilizing groups. New synthetic methodology was developed for the parallel synthesis of C-4 analogs with the new solubilizing group. Interesting new leads were evaluated in tumor xenograft models and the C-4 aminofluorobenzylindazole, 1c, was found to exhibit the best antitumor activity. It is hypothesized that this solubilizing group extends into the ribose-phosphate portion of the ATP binding pocket and enhances the binding affinity of the inhibitor.
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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 |
0960-894X
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pubmed:author |
pubmed-author:ChangMingM,
pubmed-author:ChenPingP,
pubmed-author:FinkBrian EBE,
pubmed-author:GavaiAshvinikumarA,
pubmed-author:HanWen-ChingWC,
pubmed-author:JohnsonWalterW,
pubmed-author:LangleyDavidD,
pubmed-author:LeavittKennethK,
pubmed-author:LeeFrancis YFY,
pubmed-author:MarathePunitP,
pubmed-author:MastalerzHaroldH,
pubmed-author:NorrisDerekD,
pubmed-author:OppenheimerSimoneS,
pubmed-author:SleczkaBogdanB,
pubmed-author:TarrantJamesJ,
pubmed-author:TokarskiJohn SJS,
pubmed-author:ViteGregory DGD,
pubmed-author:VyasDolatrai MDM,
pubmed-author:WongHenryH,
pubmed-author:WongTai WTW,
pubmed-author:ZhangGuifenG,
pubmed-author:ZhangHongjianH
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4947-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17606372-Adenosine Triphosphate,
pubmed-meshheading:17606372-Animals,
pubmed-meshheading:17606372-Antineoplastic Agents,
pubmed-meshheading:17606372-Cell Line, Tumor,
pubmed-meshheading:17606372-Chemistry, Pharmaceutical,
pubmed-meshheading:17606372-Drug Design,
pubmed-meshheading:17606372-Drug Screening Assays, Antitumor,
pubmed-meshheading:17606372-Humans,
pubmed-meshheading:17606372-Inhibitory Concentration 50,
pubmed-meshheading:17606372-Insects,
pubmed-meshheading:17606372-Models, Chemical,
pubmed-meshheading:17606372-Neoplasm Transplantation,
pubmed-meshheading:17606372-Neoplasms,
pubmed-meshheading:17606372-Piperidines,
pubmed-meshheading:17606372-Pyrroles,
pubmed-meshheading:17606372-Receptor, Epidermal Growth Factor,
pubmed-meshheading:17606372-Receptor, erbB-2,
pubmed-meshheading:17606372-Triazines
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pubmed:year |
2007
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pubmed:articleTitle |
5-((4-Aminopiperidin-1-yl)methyl)pyrrolotriazine dual inhibitors of EGFR and HER2 protein tyrosine kinases.
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pubmed:affiliation |
Department of Oncology Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-1951, USA. harold.mastalerz@bms.com
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pubmed:publicationType |
Journal Article
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