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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2011-1-11
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pubmed:abstractText |
Elaboration of the SAR around a series of 2,4-diaminopyrimidines led to a number of c-Met inhibitors in which kinase selectivity was modulated by substituents appended on the C4-aminobenzamide ring and the nature of the C2-aminoaryl ring. Further lead optimization of the C2-aminoaryl group led to benzoxazepine analogs whose pharmaceutical properties were modulated by the nature of the substituent on the benzoxazepine nitrogen. Tumor stasis (with partial regressions) were observed when an orally bioavailable analog was evaluated in a GTL-16 tumor xenograft mouse model. Subsequent PK/PD studies suggested that a metabolite contributed to the overall in vivo response.
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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 |
1464-3405
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pubmed:author |
pubmed-author:AimoneLisa DLD,
pubmed-author:AlbomMark SMS,
pubmed-author:AngelesThelma STS,
pubmed-author:BrownRebecca ARA,
pubmed-author:DorseyBruce DBD,
pubmed-author:GalinisDeborahD,
pubmed-author:GrobelnyJennifer VJV,
pubmed-author:HerbertzTorstenT,
pubmed-author:HustenJeanJ,
pubmed-author:KocsisLaura SLS,
pubmed-author:LoSardoChristineC,
pubmed-author:MiknyoczkiSheila JSJ,
pubmed-author:MurthySeethaS,
pubmed-author:Rolon-SteeleDamarisD,
pubmed-author:TheroffJay PJP,
pubmed-author:UnderinerTed LTL,
pubmed-author:Wells-KnechtKevin JKJ,
pubmed-author:WorrellCandace SCS,
pubmed-author:ZeiglerKelli SKS,
pubmed-author:ZificsakCraig ACA
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pubmed:copyrightInfo |
Copyright © 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
660-3
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pubmed:meshHeading |
pubmed-meshheading:21190849-Administration, Oral,
pubmed-meshheading:21190849-Animals,
pubmed-meshheading:21190849-Antineoplastic Agents,
pubmed-meshheading:21190849-Humans,
pubmed-meshheading:21190849-Mice,
pubmed-meshheading:21190849-Mice, Nude,
pubmed-meshheading:21190849-Neoplasms,
pubmed-meshheading:21190849-Protein Kinase Inhibitors,
pubmed-meshheading:21190849-Proto-Oncogene Proteins c-met,
pubmed-meshheading:21190849-Pyrimidines,
pubmed-meshheading:21190849-Xenograft Model Antitumor Assays
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pubmed:year |
2011
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pubmed:articleTitle |
2,4-Diaminopyrimidine inhibitors of c-Met kinase bearing benzoxazepine anilines.
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pubmed:affiliation |
Worldwide Discovery Research, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. czificsa@cephalon.com
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pubmed:publicationType |
Journal Article
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