309254-69-1Relevant articles and documents
Synthesis of (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-sp iro[4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties
Wichmann, Juergen,Adam, Geo,Roever, Stephan,Hennig, Michael,Scalone, Michelangelo,Cesura, Andrea M.,Dautzenberg, Frank M.,Jenck, Francois
, p. 839 - 851 (2000)
The development of 8-(2,3,3a,4,5,6-hexahydro-1H-phenalenl-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]de can-4-ones 3 starting from (RS)-8-acenaphten-1-yl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one 1 is reported. The synthesis and the binding affinities at human OFQ and opioid (μ, χ, δ) receptors of the stereoisomers 3a-f are described. In vitro the most selective compound, (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalenl-yl)-1-phenyl-1,3,8-triaza-spi ro[4.5]decan-4-one 3c, was found to act as a full agonist at the OFQ receptor in the GTPγ35S binding test. It turned out to be selective versus a variety of other neurotransmitter systems. When tested in vivo following intraperitoneal injection, compound 3c was found to decrease neophobia in a novel environment and to exhibit dose-dependent anxiolytic-like effects in the elevated plus-maze procedure, thus confirming the effects observed following intracerebroventricular infusion of the OFQ peptide in rat. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
