title: 2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective GABAA alpha3-subtype agonists.
abstract: Novel synthetic routes have been devised for the preparation of previously inaccessible 2,3,7-trisubstituted pyrazolo[1,5-d][1,2,4]triazines 2. These compounds are high affinity ligands for the GABA(A) benzodiazepine binding site and some analogues show functional selectivity for agonism at alpha3-containing receptors over alpha1-containing receptors with the lead compound being 32.
authors.affiliation: Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK. robert.carling@virgin.net
authors.forename: Robert W
authors.initials: RW
authors.lastname: Carling
authors.forename: Michael G N
authors.initials: MG
authors.lastname: Russell
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Moore
authors.forename: Andrew
authors.initials: A
authors.lastname: Mitchinson
authors.forename: Alexander
authors.initials: A
authors.lastname: Guiblin
authors.forename: Alison
authors.initials: A
authors.lastname: Smith
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wafford
authors.forename: George
authors.initials: G
authors.lastname: Marshall
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Street
mesh_terms: D001665:Binding Sites; D058785:GABA-A Receptor Agonists; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D011963:Receptors, GABA-A; D011994:Recombinant Proteins / Q000819:agonists; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D058785:GABA-A Receptor Agonists; C546257:GABRA3 protein, human; D008024:Ligands; D011720:Pyrazoles; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D014227:Triazines