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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2008-2-5
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pubmed:abstractText |
Proteolytic cleavage of amyloid precursor protein by beta-secretase (BACE-1) and gamma-secretase leads to formation of beta-amyloid (A beta) a key component of amyloid plaques, which are considered the hallmark of Alzheimer's disease. Small molecule inhibitors of BACE-1 may reduce levels of A beta and thus have therapeutic potential for treating Alzheimer's disease. We recently reported the identification of a novel small molecule BACE-1 inhibitor N-[2-(2,5-diphenyl-pyrrol-1-yl)-acetyl]guanidine (3.a.1). We report here the initial hit-to-lead optimization of this hit and the SAR around the aryl groups occupying the S(1) and S(2') pockets leading to submicromolar BACE-1 inhibitors.
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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:BardJonathanJ,
pubmed-author:ChopraRajivR,
pubmed-author:ColeDerek CDC,
pubmed-author:CowlingRebeccaR,
pubmed-author:EllingboeJohn WJW,
pubmed-author:FanKristi YKY,
pubmed-author:HarrisonBoyd LBL,
pubmed-author:HuYunY,
pubmed-author:JacobsenSteveS,
pubmed-author:JenningsLee DLD,
pubmed-author:JinGuixianG,
pubmed-author:LohsePeter APA,
pubmed-author:MalamasMichael SMS,
pubmed-author:ManasEric SES,
pubmed-author:MooreWilliam JWJ,
pubmed-author:O'DonnellMary-MargaretMM,
pubmed-author:OllandAndrea MAM,
pubmed-author:RobichaudAlbert JAJ,
pubmed-author:StockJoseph RJR,
pubmed-author:SvensonKristineK,
pubmed-author:WagnerEricE,
pubmed-author:WuJunJunJ
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1063-6
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:18162398-Alzheimer Disease,
pubmed-meshheading:18162398-Amyloid Precursor Protein Secretases,
pubmed-meshheading:18162398-Amyloid beta-Peptides,
pubmed-meshheading:18162398-Combinatorial Chemistry Techniques,
pubmed-meshheading:18162398-Crystallography, X-Ray,
pubmed-meshheading:18162398-Guanidines,
pubmed-meshheading:18162398-Molecular Conformation,
pubmed-meshheading:18162398-Molecular Structure,
pubmed-meshheading:18162398-Pyrroles,
pubmed-meshheading:18162398-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets.
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pubmed:affiliation |
Chemical & Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, NY 10965, USA. coledc@wyeth.com
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pubmed:publicationType |
Journal Article
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