1192807-40-1Relevant academic research and scientific papers
Development of 4-Heteroarylamino-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octanes] as α7 Nicotinic Receptor Agonists
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
, p. 133 - 137 (2017)
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.
