280783-56-4

Upstream product

• 309254-70-4 β-(3,4-Dihydro-1-naphthyl)propionic acid 
• 100371-82-2 2,3,3a,4,5,6-hexahydro-phenalen-1-one oxime 
• 62715-22-4 (RS)-2,3,3a,4,5,6-hexahydro-phenalen-1-one 
• 70067-71-9 (RS)-3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-propionic acid 
• 309254-78-2 (1S,3aS)-1-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-4-phenylamino-piperidine-4-carbonitrile 
• 159949-24-3 (S)-3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-propionic acid 
• 159949-23-2 (S)-2,3,3a,4,5,6-hexahydro-phenalen-1-one 
• 309254-84-0 (1S,3aR)-1-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl)-4-phenylamino-piperidine-4-carbonitrile 
• 309254-80-6 (R)-3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-propionic acid 
• 309254-81-7 (R)-2,3,3a,4,5,6-hexahydro-phenalen-1-one 

Relevant academic research and scientific papers

1,3,8-triazaspiro[4,5]decan-4-one derivatives

The present invention relates to compounds of the formula wherein R1 and R2 are each independently hydrogen, lower alkyl, lower alkoxy or halogen; R3 is phenyl, which is unsubstituted or substituted by lower alkyl, CF3, lower alkoxy or halogen; R4 is hydrogen, lower alkyl, lower alkenyl, -C(O)-lower alkyl, -C(O)-phenyl, lower alkyl-C(O)-phenyl, lower alkylene-C(O)O-lower alkyl, lower alkantriyl-di-C(O)O-lower alkyl, hydroxy-lower alkyl, lower alkyl-O-lower alkyl, lower alkyl-CH(OH)CF3, phenyl or benzyl, R5 and R6 are each independently hydrogen, phenyl, lower alkyl or di-lower alkyl or R5 and R6 together with the carbon atoms to which they are bound form a phenyl ring, or R5 and one of R1 or R2 together with the carbon atoms to which they are bound form a saturated or unsaturated 6 membered ring, A is a 4-7 membered saturated ring, their racemates and the enantiomers thereof, and the pharmaceutically acceptable acid addition salts thereof which are agonists and/or antagonists of the OFQ receptor.

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

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.