title: Discovery and pharmacological evaluation of a diphenethylamine derivative (HS665), a highly potent and selective κ opioid receptor agonist.
abstract: Here we report on the design, synthesis, and biological characterization of novel κ 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80-82, A-6020 Innsbruck, Austria.
authors.forename: Mariana
authors.initials: M
authors.lastname: Spetea
authors.forename: Ilona P
authors.initials: IP
authors.lastname: Berzetei-Gurske
authors.forename: Elena
authors.initials: E
authors.lastname: Guerrieri
authors.forename: Helmut
authors.initials: H
authors.lastname: Schmidhammer
mesh_terms: D019342:Acetic Acid / Q000633:toxicity; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D055808:Drug Discovery; D051379:Mice; D059225:Nociception / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010627:Phenethylamines / Q000138:chemical synthesis / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists*
chemical_list: C577967:3-(2-((cyclobutylmethyl)(phenethyl)amino)ethyl)phenol; D000700:Analgesics; D010627:Phenethylamines; D017473:Receptors, Opioid, kappa; D019342:Acetic Acid