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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
2011-5-2
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pubmed:abstractText |
The first highly potent and selective PDE8 inhibitors are disclosed. The initial tetrahydroisoquinoline hit was transformed into a nipecotic amide series in order to address a reactive metabolite issue. Reduction of lipophilicity to address metabolic liabilities uncovered an interesting diastereomer-dependent trend in turnover by human microsomes.
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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 |
May
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pubmed:issn |
1464-3405
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pubmed:author |
pubmed-author:AndrewsMelissa PMP,
pubmed-author:BoscoeBrian PBP,
pubmed-author:BoyerDavid DDD,
pubmed-author:DeNinnoMichael PMP,
pubmed-author:DoranShawn DSD,
pubmed-author:EtienneJohn BJB,
pubmed-author:HouseknechtKaren LKL,
pubmed-author:MillhamMichele LML,
pubmed-author:MooreDianna EDE,
pubmed-author:OlsonThanh VTV,
pubmed-author:RockeBenjamin NBN,
pubmed-author:VisserMichael SMS,
pubmed-author:WrightStephen WSW,
pubmed-author:ZarboCynthiaC
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3095-8
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pubmed:meshHeading |
pubmed-meshheading:21459572-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:21459572-Amides,
pubmed-meshheading:21459572-Enzyme Inhibitors,
pubmed-meshheading:21459572-Humans,
pubmed-meshheading:21459572-Inhibitory Concentration 50,
pubmed-meshheading:21459572-Ligands,
pubmed-meshheading:21459572-Microsomes,
pubmed-meshheading:21459572-Models, Molecular,
pubmed-meshheading:21459572-Molecular Structure,
pubmed-meshheading:21459572-Nipecotic Acids
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pubmed:year |
2011
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pubmed:articleTitle |
1,5-Substituted nipecotic amides: selective PDE8 inhibitors displaying diastereomer-dependent microsomal stability.
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pubmed:affiliation |
Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. mike_deninno@sd.vrtx.com
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pubmed:publicationType |
Journal Article
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