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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2011-2-7
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pubmed:abstractText |
Preclinical and emerging clinical evidence suggests that inhibiting insulin-like growth factor 1 receptor (IGF-1R) signaling may offer a promising therapeutic strategy for the treatment of several types of cancer. This Letter describes the medicinal chemistry effort towards a series of 8-amino-imidazo[1,5-a]pyrazine derived inhibitors of IGF-1R which features a substituted quinoline moiety at the C1 position and a cyclohexyl linking moiety at the C3 position. Lead optimization efforts which included the optimization of structure-activity relationships and drug metabolism and pharmacokinetic properties led to the identification of compound 9m, a potent, selective and orally bioavailable inhibitor of IGF-1R with in vivo efficacy in an IGF-driven mouse xenograft model.
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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 |
Feb
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:BCC,
pubmed-author:BittnerMark AMA,
pubmed-author:CookeAndyA,
pubmed-author:DongHanqingH,
pubmed-author:ForemanKennethK,
pubmed-author:GokhalePrafulla CPC,
pubmed-author:JiQunshengQ,
pubmed-author:JinMeizhongM,
pubmed-author:KleinbergAndrewA,
pubmed-author:LandfairDarlaD,
pubmed-author:MakGildaG,
pubmed-author:MulvihillKristen MKM,
pubmed-author:MulvihillMark JMJ,
pubmed-author:O'ConnorMatthewM,
pubmed-author:PachterJonathan AJA,
pubmed-author:Rosenfeld-FranklinMarylandM,
pubmed-author:SiuKam WKW,
pubmed-author:WildRobertR
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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 |
1176-80
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pubmed:meshHeading |
pubmed-meshheading:21251824-Animals,
pubmed-meshheading:21251824-Antineoplastic Agents,
pubmed-meshheading:21251824-Benzimidazoles,
pubmed-meshheading:21251824-Imidazoles,
pubmed-meshheading:21251824-Mice,
pubmed-meshheading:21251824-Neoplasms,
pubmed-meshheading:21251824-Protein Kinase Inhibitors,
pubmed-meshheading:21251824-Pyrazines,
pubmed-meshheading:21251824-Receptor, IGF Type 1,
pubmed-meshheading:21251824-Structure-Activity Relationship,
pubmed-meshheading:21251824-Transplantation, Heterologous
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pubmed:year |
2011
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pubmed:articleTitle |
Potent and selective cyclohexyl-derived imidazopyrazine insulin-like growth factor 1 receptor inhibitors with in vivo efficacy.
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pubmed:affiliation |
(OSI) Oncology, OSI Pharmaceuticals, Inc., 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. mjin@osip.com
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pubmed:publicationType |
Journal Article
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