Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective kappa opioid receptor agonist.

Article Details

Citation
Copy to clipboard

Spetea M, Berzetei-Gurske IP, Guerrieri E, Schmidhammer H

Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective kappa opioid receptor agonist.

J Med Chem. 2012 Nov 26;55(22):10302-6. doi: 10.1021/jm301258w. Epub 2012 Nov 7.

PubMed ID
23134120 [ View in PubMed
]
Abstract

Here we report on the design, synthesis, and biological characterization of novel kappa opioid (KOP) receptor ligands of diphenethylamines. In opioid receptor binding and functional assays, the N-cyclobutylmethyl substituted derivative 4 (HS665) showed the highest affinity and selectivity for the KOP receptor and KOP agonist potency. Compound 4 inhibited acetic acid induced writhing after subcutaneous administration in mice via KOP receptor-mediated mechanisms, being equipotent as an analgesic to the KOP agonist U50,488.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
DopamineDopamine D1 receptorKi (nM)4470N/AN/ADetails
DopamineDopamine D2 receptorEC 50 (nM)65N/AN/ADetails
DopamineDopamine D2 receptorKi (nM)422N/AN/ADetails
DopamineDopamine D3 receptorEC 50 (nM)6.1N/AN/ADetails
DopamineDopamine D3 receptorKi (nM)20N/AN/ADetails