86215-33-0

Upstream product

• 66504-33-4 (1S,2R)-1-(4-Methoxy-phenyl)-cyclopropane-1,2-dicarboxylic acid diethyl ester 
• 66504-34-5 (1R,2S)-1-(4-Methoxy-phenyl)-cyclopropane-1,2-dicarboxylic acid 
• 77629-83-5 ethyl 2-bromo-2-(4-methoxyphenyl) acetate 
• 14062-18-1 ethyl p-methoxyphenylacetate 
• 66504-35-6 1-(p-methoxyphenyl)-1,2-cyclopropanedicarboximide 

Relevant academic research and scientific papers

1-Aryl-3-azabicyclohexanes, a New Series of Nonnarcotic Analgesic Agents

A series of 1-aryl-3-azabicyclohexanes was synthesized by hydride reduction of 1-arylcyclopropanedicarboximides.Hydroxyphenyl analogues 20, 22, and 24 were prepared by EtSNa-DMF ether cleavage of the corresponding methoxyphenyl analogues 2m, 2n, and 23, respectively, with the secondary amines 20 and 22 going through the N-formyl intermediates 19 and 21.The p-ethoxy analogue 26 was obtained by O-ethylation of 19, followed by base hydrolysis of the amide 25.The greatest analgesic potency in mouse writhing and rat paw-pain assays was observed for para-substituted compounds.Bicifadine, 1-(4-methylphenyl)-3-azabicyclohexane (2b), was the most potent member of the series and is presently undergoing clinical trials in man.Analgesic activity of 2b is limited to the (+) enantiomer 2v, which has the 1R,5S absolute configuration as determined by single-crystal X-ray analysis.The N-methyl analogue (27d) of 2b showed significant analgesic potency, whereas the N-allyl (27a), N-(cyclopropylmethyl) (27b), and N-(n-hexyl) (27c) analogues were inactive.Bicifadine (2b) showed a nonnarcotic profile different from analogous azabicycloalkane and 3-phenylpyrrolidine analgesics.

Azabicyclohexanes

Substituted 3-azabicyclo[3.1.0]hexanes, acid addition salts, method of use and method of preparation are described. The compounds have anxiolytic and analgesic activity.