ACS Medicinal Chemistry Letters p. 133 - 137 (2017)
Update date:2022-08-04
Topics:
Hill, Matthew D.
Fang, Haiquan
King, H. Dalton
Iwuagwu, Christiana I.
McDonald, Ivar M.
Cook, James
Zusi, F. Christopher
Mate, Robert A.
Knox, Ronald J.
Post-Munson, Debra
Easton, Amy
Miller, Regina
Lentz, Kimberley
Clarke, Wendy
Benitex, Yulia
Lodge, Nicholas
Zaczek, Robert
Denton, Rex
Morgan, Daniel
Bristow, Linda
Macor, John E.
Olson, Richard
We describe the synthesis of quinuclidine-containing spiroimidates and their utility as α7 nicotinic acetylcholine receptor (nAChR) partial agonists. A convergent synthetic route allowed for rapid SAR investigation and provided a diverse set of fused 6,5-heteroaryl analogs. Two potent and selective α7 nAChR partial agonists, (1′S,3′R,4′S)-N-(7-bromopyrrolo[2,1-f ][1,2,4]triazin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (20) and (1′S,3′R,4′S)-N-(7-chloropyrrolo[2,1-f ][1,2,4]triazin-4-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (21), were identified. Both agonists improved cognition in a preclinical rodent model of learning and memory. Additionally, 5-HT3A receptor SAR suggested the presence of a steric site that when engaged led to significant loss of affinity at that receptor.
View MoreShanghai agrotree chemical co.,ltd.
Contact:+86-21-50117563
Address:Room 8A,liangfeng building,No.8 dongfang RD.pudong,shanghai,China
website:http://www.greenutra.cn
Contact:0086-411-39553357
Address:No. 7-1-1802, Huizhi Garden,Ocean Square,Dalian, 116033, China
Ji'nan Orgachem Pharmaceutical Co.,Ltd
Contact:+86-531-82687810
Address:Jinan
Zibo Linzi Darong Fine Chemical Co., Ltd(expird)
Contact:86-532-67773200; 15689126900
Address:Qidu town,Linzi district,Zibo city,Shandong province,China
Chengdu Chengnuo New-Tech Co., Ltd
Contact:0086-028-85749078
Address:4 Jiuyang road,Jiulong industrial port,Chengdu, China
Doi:10.1016/0031-9422(88)80232-2
(1988)Doi:10.1016/j.mencom.2009.09.010
(2009)Doi:10.1002/asia.201300360
(2013)Doi:10.1016/j.jorganchem.2008.12.064
(2009)Doi:10.1002/adsc.201100153
(2011)Doi:10.1016/j.jorganchem.2008.12.014
(2009)