2. Academic Validation
  3. Structure-activity relationship studies of SEN12333 analogues: determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs

Structure-activity relationship studies of SEN12333 analogues: determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs

  • Eur J Med Chem. 2015 May 5:95:277-301. doi: 10.1016/j.ejmech.2015.03.025.
Corinne Beinat 1,  Tristan Reekie 2,  Samuel D Banister 3,  James O'Brien-Brown 2,  Teresa Xie 4,  Thao T Olson 4,  Yingxian Xiao 4,  Andrew Harvey 5,  Susan O'Connor 5,  Carolyn Coles 5,  Anton Grishin 5,  Peter Kolesik 5,  John Tsanaktsidis 6,  Michael Kassiou 7
Affiliations

Affiliations

  • 1 School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia; Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2 School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
  • 3 Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 4 Department of Pharmacology and Physiology, Georgetown University, Washington, DC 20057, USA.
  • 5 Bionomics Limited, Thebarton, SA 5031, Australia.
  • 6 CSIRO Materials Science & Engineering, Ian Wark Laboratory, Bayview Avenue, Clayton, Victoria 3168, Australia.
  • 7 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.
PMID: 25827398 DOI: 10.1016/j.ejmech.2015.03.025
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).

Keywords

Acetylcholine receptor; CNS; Structure–activity relationships; α7 nicotinic receptors.

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