title: Imidazo[1,2-b][1,2,4]triazines as alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety.
abstract: Imidazo[1,2-a]pyrimidines and imidazo[1,2-b][1,2,4]triazines are ligands for the benzodiazepine binding site of GABA(A) receptors that are functionally selective for the alpha2/alpha3 subtypes over the alpha1 subtype. SAR studies to optimise this functional selectivity, pharmacokinetic and behavioural data are described.
authors.affiliation: Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. andrew_jennings@merck.com
authors.forename: Andrew S R
authors.initials: AS
authors.lastname: Jennings
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lewis
authors.forename: Michael G N
authors.initials: MG
authors.lastname: Russell
authors.forename: David J
authors.initials: DJ
authors.lastname: Hallett
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Street
authors.forename: José L
authors.initials: JL
authors.lastname: Castro
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
authors.forename: Susan M
authors.initials: SM
authors.lastname: Cook
authors.forename: Rachael
authors.initials: R
authors.lastname: Lincoln
authors.forename: Joanna
authors.initials: J
authors.lastname: Stanley
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Smith
authors.forename: David S
authors.initials: DS
authors.lastname: Reynolds
authors.forename: Bindi
authors.initials: B
authors.lastname: Sohal
authors.forename: Andrew
authors.initials: A
authors.lastname: Pike
authors.forename: George R
authors.initials: GR
authors.lastname: Marshall
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wafford
authors.forename: Wayne F A
authors.initials: WF
authors.lastname: Sheppard
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Tye
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy*; D001259:Ataxia / Q000188:drug therapy; D001665:Binding Sites; D001682:Biological Availability; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D018755:GABA Agonists / Q000493:pharmacokinetics / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D007093:Imidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015394:Molecular Structure; D021122:Protein Subunits / Q000819:agonists* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D012453:Saimiri; D013329:Structure-Activity Relationship; D014227:Triazines / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; C493920:Gabra2 protein, mouse; C546258:Gabra3 protein, mouse; D007093:Imidazoles; D021122:Protein Subunits; D011963:Receptors, GABA-A; D014227:Triazines