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N-Benzyl-N-(pyrrolidin-3-yl)carboxamides as a new class of selective dual serotonin/noradrenaline reuptake inhibitors |
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| Authors: | Wakenhut Florian Fish Paul V Fray M Jonathan Gurrell Ian Mills James E Stobie Alan Whitlock Gavin A |
| Institution: | aDepartment of Genitourinary Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK;bDepartment of Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK |
| Abstract: | The structure–activity relationship and the synthesis of novel N-benzyl-N-(pyrrolidin-3-yl)carboxamides as dual serotonin (5-HT) and noradrenaline (NA) monoamine reuptake inhibitors are described. Compounds such as 18 exhibited dual 5-HT and NA reuptake inhibition, good selectivity over dopamine (DA) reuptake inhibition and drug-like physicochemical properties consistent with CNS target space. Compound 18 was selected for further preclinical evaluation. |
| Keywords: | N-benzyl-N-(pyrrolidin-3-yl)carboxamides Serotonin reuptake Noradrenaline reuptake Metabolic profile Metabolic stability CYP2D6 inhibition Lipophilicity SNRI |
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