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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 |
4-Sulfamoyl pyrroles were designed as novel hepatoselective HMG-CoA reductase inhibitors (statins) to reduce myalgia, a statin-induced adverse effect. The compounds were prepared via a [3+2] cycloaddition of a Münchnone with a sulfonamide-substituted alkyne. We identified compounds with greater selectivity for hepatocytes compared to L6-myocytes than rosuvastatin and atorvastatin. There was an inverse correlation of myocyte potencies and ClogP values. A number of analogs were effective at reducing cholesterol in acute and chronic in vivo models but they lacked sufficient chronic in vivo activity to warrant further development.
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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:AskewValerieV,
pubmed-author:AuerbachBruceB,
pubmed-author:DillonLisaL,
pubmed-author:HanselmanJeffrey CJC,
pubmed-author:KennedyRobert MRM,
pubmed-author:KowalaMark CMC,
pubmed-author:LarsenScott DSD,
pubmed-author:LinZhiwuZ,
pubmed-author:LuGina HGH,
pubmed-author:MillerSteveS,
pubmed-author:ParkWilliam K CWK,
pubmed-author:RobertsonAndrewA,
pubmed-author:RothBruce DBD,
pubmed-author:SekerkeCatherineC,
pubmed-author:SongYuntaoY,
pubmed-author:SteinbaughBruce ABA,
pubmed-author:SunKevinK,
pubmed-author:TaitBradley DBD,
pubmed-author:TrivediBharat KBK
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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 |
1151-6
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pubmed:meshHeading |
pubmed-meshheading:18155906-Animals,
pubmed-meshheading:18155906-Combinatorial Chemistry Techniques,
pubmed-meshheading:18155906-Disease Models, Animal,
pubmed-meshheading:18155906-Fluorobenzenes,
pubmed-meshheading:18155906-Hepatocytes,
pubmed-meshheading:18155906-Heptanoic Acids,
pubmed-meshheading:18155906-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:18155906-Mice,
pubmed-meshheading:18155906-Molecular Structure,
pubmed-meshheading:18155906-Muscle Cells,
pubmed-meshheading:18155906-Pyrimidines,
pubmed-meshheading:18155906-Pyrroles,
pubmed-meshheading:18155906-Sulfonamides
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pubmed:year |
2008
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pubmed:articleTitle |
Hepatoselectivity of statins: design and synthesis of 4-sulfamoyl pyrroles as HMG-CoA reductase inhibitors.
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pubmed:affiliation |
Department of Chemistry, CVMED, Pfizer Global Research and Development, Michigan Laboratories, Ann Arbor, MI, USA. wkcpark@gmail.com
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pubmed:publicationType |
Journal Article
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