Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors.

Article Details

Citation
Copy to clipboard

Fray MJ, Bish G, Fish PV, Stobie A, Wakenhut F, Whitlock GA

Structure-activity relationships of N-substituted piperazine amine reuptake inhibitors.

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4349-53. Epub 2006 Jun 5.

PubMed ID
16750363 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DuloxetineSodium-dependent dopamine transporterIC 50 (nM)870N/AN/ADetails
DuloxetineSodium-dependent noradrenaline transporterIC 50 (nM)19N/AN/ADetails
DuloxetineSodium-dependent serotonin transporterIC 50 (nM)6N/AN/ADetails
FluoxetineSodium-dependent serotonin transporterIC 50 (nM)16N/AN/ADetails