Synthesis of (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonist with anxiolytic-like properties

Add time:07/13/2019    Source:sciencedirect.com

The development of 8-(2,3,3a,4,5,6-hexahydro-1H-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-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, κ, 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-phenalen1-yl)-1-phenyl-1,3,8-triaza-spiro[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.

We also recommend Trading Suppliers and Manufacturers of (1S,3aS)-1,5,6,8,9,14bβ-Hexahydro-2-methoxy-1α,9α-epoxy-4H-cyclopenta[a][1,3]dioxolo[4,5-h]pyrrolo[2,1-b][3]benzazepin-1β-ol (cas 49686-61-5). Pls Click Website Link as below: cas 49686-61-5 suppliers

Prev:A novel and reliable method for tetrahydrobiopterin quantification: Benzoyl chloride derivatization coupled with liquid chromatography-tandem mass spectrometry analysis
Next:PETHOXAMID (cas 106700-29-2) dissipation and microbial activity and structure in an agricultural soil: Effect of herbicide rate and organic residues)