Linked Life Data

17985862

Source:http://linkedlifedata.com/resource/pubmed/id/17985862

Statements in which the resource exists.
SubjectPredicateObjectContext
pubmed-article:17985862rdf:typepubmed:Citationlld:pubmed
pubmed-article:17985862lifeskim:mentionsumls-concept:C0178539lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0002483lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0023175lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0441655lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C1454853lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0023688lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0013682lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0185125lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0243077lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0439282lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0679622lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0079411lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C1880355lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0205314lld:lifeskim
pubmed-article:17985862lifeskim:mentionsumls-concept:C0439596lld:lifeskim
pubmed-article:17985862pubmed:issue24lld:pubmed
pubmed-article:17985862pubmed:dateCreated2007-11-26lld:pubmed
pubmed-article:17985862pubmed:databankReferencehttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:databankReferencehttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:databankReferencehttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:abstractTextFragment-based lead generation has led to the discovery of a novel series of cyclic amidine-based inhibitors of beta-secretase (BACE-1). Initial fragment hits with an isocytosine core having millimolar potency were identified via NMR affinity screening. Structure-guided evolution of these fragments using X-ray crystallography together with potency determination using surface plasmon resonance and functional enzyme inhibition assays afforded micromolar inhibitors. Similarity searching around the isocytosine core led to the identification of a related series of inhibitors, the dihydroisocytosines. By leveraging the knowledge of the ligand-BACE-1 recognition features generated from the isocytosines, the dihydroisocytosines were efficiently optimized to submicromolar potency. Compound 29, with an IC50 of 80 nM, a ligand efficiency of 0.37, and cellular activity of 470 nM, emerged as the lead structure for future optimization.lld:pubmed
pubmed-article:17985862pubmed:languageenglld:pubmed
pubmed-article:17985862pubmed:journalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:citationSubsetIMlld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:chemicalhttp://linkedlifedata.com/r...lld:pubmed
pubmed-article:17985862pubmed:statusMEDLINElld:pubmed
pubmed-article:17985862pubmed:monthNovlld:pubmed
pubmed-article:17985862pubmed:issn0022-2623lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:TianGaochaoGlld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:EdwardsPhilip...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:CampbellJames...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:ChessariGiann...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:KolmodinKarin...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:AlbertJeffrey...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:AharonyDavidDlld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:AndisikDonald...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:MaugerRussell...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:FredericksonM...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:KrumrineJenni...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:FolmerRutger...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:GeschwindnerS...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:MurrayChristo...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:CongreveMiles...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:OlssonLise-Lo...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:PatelSahilSlld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:CallaghanOwen...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:CarrRobin ARAlld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:SylvesterMark...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:KoetherGerard...lld:pubmed
pubmed-article:17985862pubmed:authorpubmed-author:SpearNateNlld:pubmed
pubmed-article:17985862pubmed:issnTypePrintlld:pubmed
pubmed-article:17985862pubmed:day29lld:pubmed
pubmed-article:17985862pubmed:volume50lld:pubmed
pubmed-article:17985862pubmed:ownerNLMlld:pubmed
pubmed-article:17985862pubmed:authorsCompleteYlld:pubmed
pubmed-article:17985862pubmed:pagination5912-25lld:pubmed
pubmed-article:17985862pubmed:dateRevised2009-11-19lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:meshHeadingpubmed-meshheading:17985862...lld:pubmed
pubmed-article:17985862pubmed:year2007lld:pubmed
pubmed-article:17985862pubmed:articleTitleApplication of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency.lld:pubmed
pubmed-article:17985862pubmed:affiliationCNS Discovery Research, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, Wilmington, DE 19850-5437, USA. philip.edwards@astrazeneca.comlld:pubmed
pubmed-article:17985862pubmed:publicationTypeJournal Articlelld:pubmed
http://linkedlifedata.com/r...http://linkedlifedata.com/r...pubmed-article:17985862lld:chembl
http://linkedlifedata.com/r...pubmed:referesTopubmed-article:17985862lld:pubmed
http://linkedlifedata.com/r...pubmed:referesTopubmed-article:17985862lld:pubmed
http://linkedlifedata.com/r...pubmed:referesTopubmed-article:17985862lld:pubmed