title: Structure-activity relationship studies of SEN12333 analogues: determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs.
abstract: Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described α7 agonist SEN12333 (8), have resulted in the identification of compound 45, a potent and selective agonist of the α7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8).
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Beinat
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Tristan
authors.initials: T
authors.lastname: Reekie
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Banister
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: James
authors.initials: J
authors.lastname: O'Brien-Brown
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University, Washington, DC 20057, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University, Washington, DC 20057, USA.
authors.forename: Thao T
authors.initials: TT
authors.lastname: Olson
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University, Washington, DC 20057, USA.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Bionomics Limited, Thebarton, SA 5031, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Harvey
authors.affiliation: Bionomics Limited, Thebarton, SA 5031, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: O'Connor
authors.affiliation: Bionomics Limited, Thebarton, SA 5031, Australia.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Coles
authors.affiliation: Bionomics Limited, Thebarton, SA 5031, Australia.
authors.forename: Anton
authors.initials: A
authors.lastname: Grishin
authors.affiliation: Bionomics Limited, Thebarton, SA 5031, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Kolesik
authors.affiliation: CSIRO Materials Science & Engineering, Ian Wark Laboratory, Bayview Avenue, Clayton, Victoria 3168, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Tsanaktsidis
authors.affiliation: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia; Faculty of Health Sciences, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: michael.kassiou@sydney.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D055808:Drug Discovery; D055724:Electrophysiological Phenomena / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D009025:Morpholines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000737:chemistry / Q000378:metabolism*
chemical_list: C540749:5-morpholin-4-ylpentanoic acid (4-pyridin-3-ylphenyl)amide; D009025:Morpholines; D011725:Pyridines; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Acetylcholine receptor; CNS; Structure–activity relationships; α7 nicotinic receptors