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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2010-2-22
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pubmed:abstractText |
This Letter describes the one pot synthesis of tertiary carbinamine 3 and related analogs of brain penetrant BACE-1 inhibitors via the alkylation of the Schiff base intermediate 2. The methodology developed for this study provided a convenient and rapid means to explore the P1 region of these types of inhibitors, where the P1 group is installed in the final step using a one-pot two-step protocol. Further SAR studies led to the identification of 10 which is twofold more potent in vitro as compared to the lead compound. This inhibitor was characterized in a cisterna magna ported rhesus monkey model, where significant lowering of CSF Abeta40 was observed.
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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 |
1464-3405
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pubmed:author |
pubmed-author:ColussiDennisD,
pubmed-author:CookJacquelynn JJJ,
pubmed-author:GrahamSamuel LSL,
pubmed-author:HazudaDaria JDJ,
pubmed-author:HolahanMarie AMA,
pubmed-author:LaiMing-TainMT,
pubmed-author:MichenerMaria SMS,
pubmed-author:NantermetPhilippe GPG,
pubmed-author:PietrakBethB,
pubmed-author:PriceEric AEA,
pubmed-author:RajapakseHemaka AHA,
pubmed-author:SankaranarayananSethuS,
pubmed-author:ShiXiao-PingXP,
pubmed-author:SimonAdamA,
pubmed-author:TugushevaKatherineK,
pubmed-author:VaccaJoseph PJP,
pubmed-author:YoungMary BMB,
pubmed-author:ZhuHongH
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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 |
1
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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 |
1779-82
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:20122828-Amyloid Precursor Protein Secretases,
pubmed-meshheading:20122828-Amyloid beta-Peptides,
pubmed-meshheading:20122828-Animals,
pubmed-meshheading:20122828-Aspartic Acid Endopeptidases,
pubmed-meshheading:20122828-Brain,
pubmed-meshheading:20122828-Enzyme Inhibitors,
pubmed-meshheading:20122828-Humans,
pubmed-meshheading:20122828-Macaca mulatta,
pubmed-meshheading:20122828-Oxadiazoles,
pubmed-meshheading:20122828-Peptide Fragments,
pubmed-meshheading:20122828-Structure-Activity Relationship,
pubmed-meshheading:20122828-Sulfonamides
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pubmed:year |
2010
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pubmed:articleTitle |
Rapid P1 SAR of brain penetrant tertiary carbinamine derived BACE inhibitors.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
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pubmed:publicationType |
Journal Article
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