Structure-activity relationships of N-substituted ligands for the alpha7 nicotinic acetylcholine receptor.
A series of alpha7 neuronal nicotinic acetylcholine receptor ligands were designed based on a structural combination of a potent, but non-selective ligand, epibatidine, with a selective lead structure, 2. Three series of compounds in which aryl moieties were attached via a linker to different positions on the core structure were studied. A potent and functionally efficacious analog, (3aR,6aS)-2-(6-phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)octahydropyrrolo[3,4-c]pyrrole (3a), was identified.
Mortell
Kathleen H
KH
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. kathleen.mortell@abbott.com
Schrimpf
Michael R
MR
Bunnelle
William H
WH
Anderson
David J
DJ
Gronlien
Jens Halvard
JH
Hagene
Kirsten Thorin
KT
Gopalakrishnan
Murali
M
D000818:Animals; D006801:Humans; D008024:Ligands; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014981:Xenopus; D064569:alpha7 Nicotinic Acetylcholine Receptor
C549130:2-(6-phenylpyridazin-3-yl)-5-(pyridin-3-ylmethyl)octahydropyrrolo(3,4-c)pyrrole; C579167:Chrna7 protein, human; D008024:Ligands; D018722:Nicotinic Agonists; D011724:Pyridazines; D011758:Pyrroles; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor