title: A pyridazine series of alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety.
abstract: The development of a series of GABA(A) alpha2/alpha3 subtype selective pyridazine based benzodiazepine site agonists as anxiolytic agents with reduced sedative/ataxic potential is described, including the discovery of 16, a remarkably alpha3-selective compound ideal for in vivo study. These ligands are antagonists at the alpha1 subtype, with good CNS penetration and receptor occupancy, and excellent oral bioavailability.
authors.affiliation: The Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom. richard_t_lewis@btinternet.com
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lewis
authors.forename: Wesley P
authors.initials: WP
authors.lastname: Blackaby
authors.forename: Timothy
authors.initials: T
authors.lastname: Blackburn
authors.forename: Andrew S R
authors.initials: AS
authors.lastname: Jennings
authors.forename: Andrew
authors.initials: A
authors.lastname: Pike
authors.forename: Rowan A
authors.initials: RA
authors.lastname: Wilson
authors.forename: David J
authors.initials: DJ
authors.lastname: Hallett
authors.forename: Susan M
authors.initials: SM
authors.lastname: Cook
authors.forename: Pushpinder
authors.initials: P
authors.lastname: Ferris
authors.forename: George R
authors.initials: GR
authors.lastname: Marshall
authors.forename: David S
authors.initials: DS
authors.lastname: Reynolds
authors.forename: Wayne F A
authors.initials: WF
authors.lastname: Sheppard
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Smith
authors.forename: Bindi
authors.initials: B
authors.lastname: Sohal
authors.forename: Joanna
authors.initials: J
authors.lastname: Stanley
authors.forename: Spencer J
authors.initials: SJ
authors.lastname: Tye
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wafford
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy*; D001665:Binding Sites; D018755:GABA Agonists / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011724:Pyridazines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins / Q000819:agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D008024:Ligands; D011724:Pyridazines; D011994:Recombinant Proteins