Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors.
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.
Fray
M Jonathan
MJ
Sandwich Chemistry, Pfizer Global Research and Development, Kent, UK. jonathan.fray@pfizer.com
Bish
Gerwyn
G
Fish
Paul V
PV
Stobie
Alan
A
Wakenhut
Florian
F
Whitlock
Gavin A
GA
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
D000588:Amines; D000077489:Piperazine; D010879:Piperazines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors