N-Benzyl-N-(pyrrolidin-3-yl)carboxamides as a new class of selective dual serotonin/noradrenaline reuptake inhibitors.
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.
Wakenhut
Florian
F
Department of Genitourinary Chemistry, Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. florian.wakenhut@pfizer.com
Fish
Paul V
PV
Fray
M Jonathan
MJ
Gurrell
Ian
I
Mills
James E
JE
Stobie
Alan
A
Whitlock
Gavin A
GA
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
D000577:Amides; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D018765:Dopamine Uptake Inhibitors; D009638:Norepinephrine; D011759:Pyrrolidines; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors