Journal of Medicinal Chemistry p. 481 - 490 (1981)
Update date:2022-07-29
Topics:
Epstein, Joseph W.
Brabander, Herbert J.
Fanshawe, William J.
Hofmann, Corris M.
McKenzie, Thomas C.
et al.
A series of 1-aryl-3-azabicyclo<3.1.0>hexanes 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-azabicyclo<3.1.0>hexane (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.
View MoreShandong Jincheng Zhonghua Bio-pharmaceutical Co.,Ltd
Contact:+86-533-5415882
Address:Zichuan Economic Development Zone,Zibo City,Shandong Province,China
Xi'an caijing Opto-Electrical Science & Technology Co., LTD
Contact:+86-29-88294447
Address:NO.168 Zhangba Rd. East, Xi'an, P.R.China
Contact:86-310-8067016
Address:East Fuhua Road,Tiexi Chemical Industrial Estate,Hebei,China
Zibo Jujin Chemical Industry Co., Ltd.(Dongming Jujin Chemical Industry Co., Ltd. )
Contact:+86-533-2975022
Address:No.99 Shanquan Road, Zhangdian District
website:http://www.easchem.com
Contact:+86-731-89722861 89722891
Address:2/F-4/Bld Colorful Palace, No.605 Changsha Ave, Yuhua Area Changsha Hunan China.
Doi:10.1002/ejoc.200300474
(2004)Doi:10.1039/DT9770002139
()Doi:10.1002/adsc.201800366
(2018)Doi:10.1080/00304940409355375
(2004)Doi:10.1002/jhet.2374
(2016)Doi:10.1002/anie.200351886
(2004)