Abstract:
:The structure-activity relationship and the synthesis of novel N-[(3S)-pyrrolidin-3-yl]benzamides as dual serotonin and noradrenaline monoamine reuptake inhibitors (SNRI) is described. Preferred compound 9 aka PF-184,298 is a potent SNRI with good selectivity over dopamine reuptake inhibition (DRI), good in vitro metabolic stability, weak CYP inhibition and drug-like physicochemical properties consistent with CNS target space. Evaluation in an in vivo preclinical model of stress urinary incontinence showed 9 significantly increased urethral tone at free plasma concentrations consistent with its in vitro primary pharmacology.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Wakenhut F,Allan GA,Fish PV,Fray MJ,Harrison AC,McCoy R,Phillips SC,Ryckmans T,Stobie A,Westbrook D,Westbrook SL,Whitlock GAdoi
10.1016/j.bmcl.2009.07.049subject
Has Abstractpub_date
2009-09-01 00:00:00pages
5078-81issue
17eissn
0960-894Xissn
1464-3405pii
S0960-894X(09)01001-4journal_volume
19pub_type
杂志文章abstract::A new synthesis of (R,S)-PPG (4-phosphonophenylglycine) and the separation of the protected enantiomers leading after deprotection to (+)- and (-)-PPG are described. Pharmacological characterization at the group III metabotropic glutamate receptors hmGluR4a and hmGluR7b revealed (+)-PPG as the active enantiomer. ...
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
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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
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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
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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
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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
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