title: Structure-activity relationships of N-substituted 4-(trifluoromethoxy)benzamidines with affinity for GluN2B-containing NMDA receptors.
abstract: GluN2B subtype-selective NMDA antagonists represent promising therapeutic targets for the symptomatic treatment of multiple CNS pathologies. A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic moieties. Compounds were evaluated for activity at GluN2B containing NMDA receptors where analogues 9, 12, 16 and 18 were the most potent of the series, replacement of the benzyl ring with polycycles resulted in a complete loss of activity.
authors.affiliation: School of Chemistry, The University of Sydney, NSW 2006, Australia.
authors.forename: Corinne
authors.initials: C
authors.lastname: Beinat
authors.affiliation: School of Chemistry, The University of Sydney, NSW 2006, Australia; Brain and Mind Research Institute, Sydney, NSW 2050, Australia.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Banister
authors.affiliation: School of Chemistry, The University of Sydney, NSW 2006, Australia.
authors.forename: Jane
authors.initials: J
authors.lastname: Hoban
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: Department of Radiology & Nuclear Medicine, VU University Medical Centre, Amsterdam 1081HV, The Netherlands.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Metaxas
authors.affiliation: Department of Radiology & Nuclear Medicine, VU University Medical Centre, Amsterdam 1081HV, The Netherlands.
authors.forename: Albert D
authors.initials: AD
authors.lastname: Windhorst
authors.affiliation: School of Chemistry, The University of Sydney, NSW 2006, Australia; Brain and Mind Research Institute, Sydney, NSW 2050, Australia; Discipline of Medical Radiation Sciences, University of Sydney, NSW 2006, Australia. Electronic address: michael.kassiou@sydney.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Kassiou
mesh_terms: D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D005461:Fluorine / Q000737:chemistry*; D005971:Glutamates / Q000737:chemistry* / Q000378:metabolism; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C539201:4-trifluoromethoxy-N-(2-trifluoromethylbenzyl)benzamidine; D001550:Benzamidines; D005971:Glutamates; D011083:Polycyclic Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D005461:Fluorine
keywords: Amidine; CNS; GluN2B; NMDA; Structure–activity relationships