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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
19
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pubmed:dateCreated |
2008-9-23
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pubmed:abstractText |
We describe here orally active and brain-penetrant cathepsin S selective inhibitors, which are virtually devoid of hERG K(+) channel affinity, yet exhibit nanomolar potency against cathepsin S and over 100-fold selectivity to cathepsin L. The new non-peptidic inhibitors are based on a 2-cyanopyrimidine scaffold bearing a spiro[3.5]non-6-yl-methyl amine at the 4-position. The brain-penetrating cathepsin S inhibitors demonstrate potential clinical utility for the treatment of multiple sclerosis and neuropathic pain.
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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 |
Oct
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:BevanStuart JSJ,
pubmed-author:CulshawAndrew JAJ,
pubmed-author:EharaTakeruT,
pubmed-author:FoxAlyson JAJ,
pubmed-author:GunjiHirokiH,
pubmed-author:HallettAllanA,
pubmed-author:HartTerance WTW,
pubmed-author:HiestandPeter CPC,
pubmed-author:HiraoHajimeH,
pubmed-author:HitomiYukoY,
pubmed-author:IrieOsamuO,
pubmed-author:IwakiYukiY,
pubmed-author:IwasakiAtsukoA,
pubmed-author:IwasakiGenjiG,
pubmed-author:KanazawaTakanoriT,
pubmed-author:KishidaMasashiM,
pubmed-author:KonishiKazuhideK,
pubmed-author:KosakaTakatoshiT,
pubmed-author:MalcangioMarziaM,
pubmed-author:MasuyaKeiichiK,
pubmed-author:SakakiJunichiJ,
pubmed-author:TanabeKeikoK,
pubmed-author:TenoNaokiN,
pubmed-author:ToyaoAtsushiA,
pubmed-author:YaqoobMohammedM,
pubmed-author:YokokawaFumiakiF
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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 |
5280-4
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18783943-Administration, Oral,
pubmed-meshheading:18783943-Animals,
pubmed-meshheading:18783943-Brain,
pubmed-meshheading:18783943-Cathepsin L,
pubmed-meshheading:18783943-Cathepsins,
pubmed-meshheading:18783943-Combinatorial Chemistry Techniques,
pubmed-meshheading:18783943-Cysteine Endopeptidases,
pubmed-meshheading:18783943-Ether-A-Go-Go Potassium Channels,
pubmed-meshheading:18783943-Humans,
pubmed-meshheading:18783943-Male,
pubmed-meshheading:18783943-Molecular Structure,
pubmed-meshheading:18783943-Multiple Sclerosis,
pubmed-meshheading:18783943-Pain,
pubmed-meshheading:18783943-Pyrimidines,
pubmed-meshheading:18783943-Rats,
pubmed-meshheading:18783943-Rats, Sprague-Dawley,
pubmed-meshheading:18783943-Structure-Activity Relationship
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pubmed:year |
2008
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pubmed:articleTitle |
Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-cyanopyrimidines. Part 2.
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pubmed:affiliation |
Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Ohkubo 8, Tsukuba, Ibaraki 300-2611, Japan. osamu.irie@novartis.com
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pubmed:publicationType |
Journal Article
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