86215-53-4Relevant academic research and scientific papers
METHODS AND COMPOSITIONS FOR THE TREATMENT OF NEUROPATHIES AND RELATED DISORDERS
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Page/Page column 45-46, (2010/11/25)
The present invention provides novel compositions and methods for treating symptoms associated with neuropathic disorders such as hyperalgesia, allodynia, and parasthesias, using a l-aryl-3-azabicyclo[3.1.0] hexane. The invention further relates to the us
METHODS AND COMPOSITIONS FOR PRODUCTION, FORMULATION AND USE OF 1-ARYL-3-AZABICYCLO[3.1.0] HEXANES
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Page/Page column 77, (2010/11/23)
The invention provides novel l-aryl-3-azabicyclo[3.1.0] hexanes that are active for modulating biogenic amine transport, along with compositions and methods for using these compounds to treat central nervous system disorders. Certain l-aryl-3-azabicyclo[3.1.0] hexanes are provided that have at least one substituent on the aryl ring. In other embodiments l-aryl-3-azabicyclo[3.1.0] hexanes are provided that have a substitution on the nitrogen at the '3' position. In additional embodiments l-aryl-3-azabicyclo[3.1.0] hexanes are provided which have one substitution on the aryl ring, as well as a substitution on the nitrogen at the '3' position. The invention also provides novel methods of making aryl- and aza-substituted l-aryl-3-azabicyclo[3.1.0] hexanes, including synthetic methods that form novel intermediate compounds of the invention for producing aryl- and aza-substituted l-aryl-3-azabicyclo[3.1.0] hexanes.
1-Aryl-3-azabicyclohexanes, a New Series of Nonnarcotic Analgesic Agents
Epstein, Joseph W.,Brabander, Herbert J.,Fanshawe, William J.,Hofmann, Corris M.,McKenzie, Thomas C.,et al.
, p. 481 - 490 (2007/10/02)
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.
