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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 |
2007-2-23
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pubmed:abstractText |
A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.
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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 |
0960-894X
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pubmed:author |
pubmed-author:BarrowJames CJC,
pubmed-author:CollusiDennisD,
pubmed-author:EspesethAmy SAS,
pubmed-author:GrahamSamuel LSL,
pubmed-author:GregroAlison RAR,
pubmed-author:HochmanJerome HJH,
pubmed-author:HollowayM KatharineMK,
pubmed-author:LaiMing-TainMT,
pubmed-author:McGaugheyGeorgia BGB,
pubmed-author:MunshiSanjeev KSK,
pubmed-author:NantermetPhilippe GPG,
pubmed-author:PietrakBeth LBL,
pubmed-author:RittleKenneth EKE,
pubmed-author:SelnickHarold GHG,
pubmed-author:ShafferJennifer RJR,
pubmed-author:SimonAdam JAJ,
pubmed-author:StantonMatthew GMG,
pubmed-author:StaufferShaun RSR,
pubmed-author:SteinbeiserMelissa AMA,
pubmed-author:VaccaJoseph PJP
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1788-92
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17257835-Amyloid Precursor Protein Secretases,
pubmed-meshheading:17257835-Animals,
pubmed-meshheading:17257835-Aspartic Acid Endopeptidases,
pubmed-meshheading:17257835-Baculoviridae,
pubmed-meshheading:17257835-Biological Availability,
pubmed-meshheading:17257835-Cells, Cultured,
pubmed-meshheading:17257835-Enzyme Inhibitors,
pubmed-meshheading:17257835-Magnetic Resonance Spectroscopy,
pubmed-meshheading:17257835-Models, Molecular,
pubmed-meshheading:17257835-Molecular Conformation,
pubmed-meshheading:17257835-Molecular Weight,
pubmed-meshheading:17257835-Niacinamide,
pubmed-meshheading:17257835-Rats,
pubmed-meshheading:17257835-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation.
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pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. shaun_stauffer@merck.com
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pubmed:publicationType |
Journal Article
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