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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2006-7-17
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pubmed:abstractText |
Recently, we reported potent and small-sized beta-secretase (BACE1) inhibitors KMI-570 and KMI-684 in which we replaced carboxylic acid groups at the P(1)(') position of KMI-420 and KMI-429, respectively, with tetrazole derivatives as carboxylic acid bioisosteres. These modifications improved significantly BACE1 inhibitory activity and chemical stability. In this study, the acidic tetrazole ring of the P(4) position of KMI-420 and KMI-570, respectively, was replaced with various hydrogen bond acceptor groups. We found BACE1 inhibitor KMI-574 that exhibited potent inhibitory activity in cultured cells as well as in vitro enzymatic assay.
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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 |
Aug
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:EbinaMaikoM,
pubmed-author:HamadaYoshioY,
pubmed-author:HayashiYoshioY,
pubmed-author:HidakaKoushiK,
pubmed-author:IgawaNaotoN,
pubmed-author:IkariHayatoH,
pubmed-author:IshiuraShoichiS,
pubmed-author:KimuraTooruT,
pubmed-author:KisoYoshiakiY,
pubmed-author:NguyenJeffrey-TriJT,
pubmed-author:SaitoKazukiK,
pubmed-author:YamaniAbdellahA,
pubmed-author:ZioraZytaZ
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4354-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16757166-Amyloid Precursor Protein Secretases,
pubmed-meshheading:16757166-Aspartic Acid Endopeptidases,
pubmed-meshheading:16757166-Carboxylic Acids,
pubmed-meshheading:16757166-Cells, Cultured,
pubmed-meshheading:16757166-Chemistry, Pharmaceutical,
pubmed-meshheading:16757166-Drug Design,
pubmed-meshheading:16757166-Endopeptidases,
pubmed-meshheading:16757166-Esters,
pubmed-meshheading:16757166-Humans,
pubmed-meshheading:16757166-Models, Chemical,
pubmed-meshheading:16757166-Models, Molecular,
pubmed-meshheading:16757166-Protease Inhibitors,
pubmed-meshheading:16757166-Tetrazoles
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pubmed:year |
2006
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pubmed:articleTitle |
beta-Secretase inhibitors: modification at the P4 position and improvement of inhibitory activity in cultured cells.
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pubmed:affiliation |
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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