title: Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors.
abstract: We report the structure-activity relationships of further analogues in a series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake, that is, with additional substitution of the phenyl rings, or their replacement by heterocycles. The enantiomers of compounds 1 and 2 were also profiled, and possessed drug-like physicochemical properties. In particular, compound (-)-2 lacked potent inhibitory activity against any of the important cytochromes P(450) and high selectivity over a wide range of receptors, which is unusual for a compound that inhibits human amine transporters.
authors.affiliation: Sandwich Chemistry, Pfizer Global Research and Development, Kent, UK. jonathan.fray@pfizer.com
authors.forename: M Jonathan
authors.initials: MJ
authors.lastname: Fray
authors.forename: Gerwyn
authors.initials: G
authors.lastname: Bish
authors.forename: Paul V
authors.initials: PV
authors.lastname: Fish
authors.forename: Alan
authors.initials: A
authors.lastname: Stobie
authors.forename: Florian
authors.initials: F
authors.lastname: Wakenhut
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Whitlock
mesh_terms: D000588:Amines / Q000737:chemistry; D001692:Biological Transport; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000077489:Piperazine; D010879:Piperazines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors