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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2010-3-18
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pubmed:abstractText |
The discovery of new highly potent and selective triple reuptake inhibitors is reported. The new classes of 1-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes are described together with detailed SAR. Appropriate decoration of the scaffolds was achieved with the help of a triple reuptake inhibitor pharmacophore model detailed here. Selected derivatives showed good oral bioavailability (>30%) and brain penetration (B/B > 4) in rats associated with high in vitro potency and selectivity at SERT, NET, and DAT. Among these compounds, microdialysis and in vivo experiments confirm that derivative 15 has an appropriate developability profile to be considered for further progression.
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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 |
Mar
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pubmed:issn |
1520-4804
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pubmed:author |
pubmed-author:ArbanRobertoR,
pubmed-author:BenedettiRobertoR,
pubmed-author:BertaniBarbaraB,
pubmed-author:BettatiMichelaM,
pubmed-author:BetteliniLetiziaL,
pubmed-author:BonanomiGiorgioG,
pubmed-author:BraggioSimoneS,
pubmed-author:CavanniPaoloP,
pubmed-author:ChecchiaAnnaA,
pubmed-author:DavalliSilviaS,
pubmed-author:Di FabioRomanoR,
pubmed-author:FazzolariElettraE,
pubmed-author:FontanaStefanoS,
pubmed-author:MarchioroCarlaC,
pubmed-author:MicheliFabrizioF,
pubmed-author:MinickDougD,
pubmed-author:NegriMicheleM,
pubmed-author:OliosiBeatriceB,
pubmed-author:ReadKevin DKD,
pubmed-author:SartoriIlariaI,
pubmed-author:TarsiLucaL,
pubmed-author:TedescoGiovannaG,
pubmed-author:TerreniSilviaS,
pubmed-author:VisentiniFilippoF,
pubmed-author:ZocchiAlessandroA,
pubmed-author:ZonziniLauraL
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2534-51
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pubmed:meshHeading |
pubmed-meshheading:20170186-Animals,
pubmed-meshheading:20170186-Azabicyclo Compounds,
pubmed-meshheading:20170186-Binding, Competitive,
pubmed-meshheading:20170186-Biogenic Monoamines,
pubmed-meshheading:20170186-Biological Availability,
pubmed-meshheading:20170186-Biological Transport,
pubmed-meshheading:20170186-Cell Line,
pubmed-meshheading:20170186-Chromatography, High Pressure Liquid,
pubmed-meshheading:20170186-Cytochrome P-450 Enzyme System,
pubmed-meshheading:20170186-Dopamine Plasma Membrane Transport Proteins,
pubmed-meshheading:20170186-Humans,
pubmed-meshheading:20170186-Male,
pubmed-meshheading:20170186-Mice,
pubmed-meshheading:20170186-Microdialysis,
pubmed-meshheading:20170186-Microsomes, Liver,
pubmed-meshheading:20170186-Models, Chemical,
pubmed-meshheading:20170186-Molecular Structure,
pubmed-meshheading:20170186-Motor Activity,
pubmed-meshheading:20170186-Norepinephrine Plasma Membrane Transport Proteins,
pubmed-meshheading:20170186-Prefrontal Cortex,
pubmed-meshheading:20170186-Rats,
pubmed-meshheading:20170186-Serotonin Plasma Membrane Transport Proteins,
pubmed-meshheading:20170186-Structure-Activity Relationship
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pubmed:year |
2010
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pubmed:articleTitle |
1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: a new series of potent and selective triple reuptake inhibitors.
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pubmed:affiliation |
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline Medicine Research Centre, Via Fleming 4, 37135 Verona, Italy. Fabrizio.E.Micheli@gsk.com
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pubmed:publicationType |
Journal Article
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