title: N-Benzyl-N-(pyrrolidin-3-yl)carboxamides as a new class of selective dual serotonin/noradrenaline reuptake inhibitors.
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.
authors.affiliation: Department of Genitourinary Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. florian.wakenhut@pfizer.com
authors.forename: Florian
authors.initials: F
authors.lastname: Wakenhut
authors.forename: Paul V
authors.initials: PV
authors.lastname: Fish
authors.forename: M Jonathan
authors.initials: MJ
authors.lastname: Fray
authors.forename: Ian
authors.initials: I
authors.lastname: Gurrell
authors.forename: James E
authors.initials: JE
authors.lastname: Mills
authors.forename: Alan
authors.initials: A
authors.lastname: Stobie
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Whitlock
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004285:Dogs; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D015195:Drug Design; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008968:Molecular Conformation; D009638:Norepinephrine / Q000032:analysis*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D018765:Dopamine Uptake Inhibitors; D009638:Norepinephrine; D011759:Pyrrolidines; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors