Syntheses and structure-activity relationship (SAR) studies of 2,5-diazabicyclo[2.2.1]heptanes as novel alpha7 neuronal nicotinic receptor (NNR) ligands.
Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha7 NNR agonist activity.
Li
Tao
T
Neuroscience Research, GPRD, Abbott, Abbott Park, IL 60064-6117, USA. Tao.Li@abbott.com
Bunnelle
William H
WH
Ryther
Keith B
KB
Anderson
David J
DJ
Malysz
John
J
Helfrich
Rosalind
R
Grønlien
Jens H
JH
Håkerud
Monika
M
Peters
Dan
D
Schrimpf
Michael R
MR
Gopalakrishnan
Murali
M
Ji
Jianguo
J
D000818:Animals; D006536:Heptanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D009474:Neurons / Q000378:metabolism; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D006536:Heptanes; D008024:Ligands; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic