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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 |
2010-2-3
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pubmed:abstractText |
We report herein a novel series of difluoropiperidine acetic acids as modulators of gamma-secretase. Synthesis of 2-aryl-3,3-difluoropiperidine analogs was facilitated by a unique and selective beta-difluorination with Selectfluor. Compounds 1f and 2c were selected for in vivo assessment and demonstrated selective lowering of Abeta42 in a genetically engineered mouse model of APP processing. Moreover, in a 7-day safety study, rats treated orally with compound 1f (250mg/kg per day, AUC(0-24)=2100microMh) did not exhibit Notch-related effects.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Acetic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid Precursor Protein Secretases,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Diazonium Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42),
http://linkedlifedata.com/resource/pubmed/chemical/selectfluor
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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:AndradePaulaP,
pubmed-author:AngagawMinilikM,
pubmed-author:BiGraceG,
pubmed-author:BlackRegina MRM,
pubmed-author:CrispinoJamieJ,
pubmed-author:CruzJonathan CJC,
pubmed-author:EleyB MBM,
pubmed-author:FarrisGeorgiaG,
pubmed-author:HamblettChristopherC,
pubmed-author:HubbsJedJ,
pubmed-author:HughesBethany LBL,
pubmed-author:KenificCandia MCM,
pubmed-author:MiddletonRichard ERE,
pubmed-author:MunozBenitoB,
pubmed-author:NikovGeorgeG,
pubmed-author:SajonzPeterP,
pubmed-author:ShahSanjivS,
pubmed-author:ShearmanMarkM,
pubmed-author:ShomerNirahN,
pubmed-author:SlomanDavidD,
pubmed-author:StantonMatthew GMG,
pubmed-author:SzewczakAlexander AAA,
pubmed-author:TangaFlobertF,
pubmed-author:TudgeMatthew TMT
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pubmed:copyrightInfo |
Copyright 2009 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 |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
755-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20005099-Acetic Acids,
pubmed-meshheading:20005099-Amyloid Precursor Protein Secretases,
pubmed-meshheading:20005099-Amyloid beta-Peptides,
pubmed-meshheading:20005099-Animals,
pubmed-meshheading:20005099-Diazonium Compounds,
pubmed-meshheading:20005099-Disease Models, Animal,
pubmed-meshheading:20005099-Fluorine,
pubmed-meshheading:20005099-Mice,
pubmed-meshheading:20005099-Mice, Transgenic,
pubmed-meshheading:20005099-Peptide Fragments,
pubmed-meshheading:20005099-Piperidines,
pubmed-meshheading:20005099-Rats,
pubmed-meshheading:20005099-Receptors, Notch
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pubmed:year |
2010
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pubmed:articleTitle |
Fluorinated piperidine acetic acids as gamma-secretase modulators.
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pubmed:affiliation |
Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. matthew_stanton@merck.com
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pubmed:publicationType |
Journal Article
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