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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2008-3-20
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pubmed:abstractText |
A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.
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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 |
Mar
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BorgGeorgeG,
pubmed-author:BreadyJamesJ,
pubmed-author:ChenDanlinD,
pubmed-author:ChoquetteDeborahD,
pubmed-author:CoxonAngelaA,
pubmed-author:DeMelfiTomT,
pubmed-author:DiPietroLucianL,
pubmed-author:DoerrNicholasN,
pubmed-author:EstradaJuanJ,
pubmed-author:FlynnJulieJ,
pubmed-author:GermainJulieJ,
pubmed-author:GraceffaRussell FRF,
pubmed-author:HarmangeJean-ChristopheJC,
pubmed-author:HarrimanShawn PSP,
pubmed-author:KaufmanStephenS,
pubmed-author:LaDaniel SDS,
pubmed-author:LongAlexanderA,
pubmed-author:MartinMatthew WMW,
pubmed-author:NeervannanSeshaS,
pubmed-author:PatelVinod FVF,
pubmed-author:PolverinoAnthony JAJ,
pubmed-author:PotashmanMicheleM,
pubmed-author:RegalKellyK,
pubmed-author:RovetoPhillip MPM,
pubmed-author:SchragMichael LML,
pubmed-author:StarnesCharlieC,
pubmed-author:TaskerAndrewA,
pubmed-author:TefferaYohannesY,
pubmed-author:WangLingL,
pubmed-author:WeissMatthew MMM,
pubmed-author:WhiteRyan DRD,
pubmed-author:WhittingtonDouglas ADA,
pubmed-author:ZanonRogerR
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pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
51
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1649-67
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18324761-Administration, Oral,
pubmed-meshheading:18324761-Animals,
pubmed-meshheading:18324761-Antineoplastic Agents,
pubmed-meshheading:18324761-Cell Line, Tumor,
pubmed-meshheading:18324761-Cell Proliferation,
pubmed-meshheading:18324761-Corneal Neovascularization,
pubmed-meshheading:18324761-Crystallography, X-Ray,
pubmed-meshheading:18324761-Dose-Response Relationship, Drug,
pubmed-meshheading:18324761-Drug Design,
pubmed-meshheading:18324761-Drug Evaluation, Preclinical,
pubmed-meshheading:18324761-Endothelial Cells,
pubmed-meshheading:18324761-Female,
pubmed-meshheading:18324761-Humans,
pubmed-meshheading:18324761-Inhibitory Concentration 50,
pubmed-meshheading:18324761-Injections, Intravenous,
pubmed-meshheading:18324761-Male,
pubmed-meshheading:18324761-Mice,
pubmed-meshheading:18324761-Mice, Inbred BALB C,
pubmed-meshheading:18324761-Mice, Nude,
pubmed-meshheading:18324761-Microsomes, Liver,
pubmed-meshheading:18324761-Models, Molecular,
pubmed-meshheading:18324761-Molecular Structure,
pubmed-meshheading:18324761-Naphthalenes,
pubmed-meshheading:18324761-Protein Kinase Inhibitors,
pubmed-meshheading:18324761-Protein-Tyrosine Kinases,
pubmed-meshheading:18324761-Rats,
pubmed-meshheading:18324761-Rats, Sprague-Dawley,
pubmed-meshheading:18324761-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:18324761-Reproducibility of Results,
pubmed-meshheading:18324761-Stereoisomerism,
pubmed-meshheading:18324761-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Naphthamides as novel and potent vascular endothelial growth factor receptor tyrosine kinase inhibitors: design, synthesis, and evaluation.
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pubmed:affiliation |
Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Cambridge, MA 02139, USA. harmange@amgen.com
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pubmed:publicationType |
Journal Article
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