Abstract:
:A novel class of 4-substituted-8-(1-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu opioid receptor as well as the nociceptin/orphanin FQ peptide (NOP) receptor. These molecules also exhibit superior pharmacological and pharmacokinetic parameters, relative to all GlyT1 inhibitors of the spiropiperidine family, culminating in the identification of 16b with an oral bioavailability of approximately 60%. In addition, a straightforward two-step procedure for the assembly of the target molecules is also presented.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Alberati D,Hainzl D,Jolidon S,Kurt A,Pinard E,Thomas AW,Zimmerli Ddoi
10.1016/j.bmcl.2006.05.063subject
Has Abstractpub_date
2006-08-15 00:00:00pages
4321-5issue
16eissn
0960-894Xissn
1464-3405pii
S0960-894X(06)00601-9journal_volume
16pub_type
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journal_title:Bioorganic & medicinal chemistry letters
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更新日期:2005-06-02 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
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更新日期:2018-02-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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doi:10.1016/j.bmcl.2017.09.065
更新日期:2017-12-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(03)00172-0
更新日期:2003-04-17 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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更新日期:2007-05-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2008.01.106
更新日期:2008-03-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.07.057
更新日期:2013-10-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2017.08.044
更新日期:2017-10-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(00)00634-x
更新日期:2001-01-22 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
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更新日期:2014-02-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2007.03.068
更新日期:2007-06-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2012.08.082
更新日期:2012-11-01 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/j.bmcl.2013.06.072
更新日期:2013-09-15 00:00:00
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journal_title:Bioorganic & medicinal chemistry letters
pub_type: 杂志文章
doi:10.1016/s0960-894x(98)00382-5
更新日期:1998-08-18 00:00:00