2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective GABAA alpha3-subtype agonists.
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.
Carling
Robert W
RW
Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre, Terlings Park, Harlow, Essex, CM20 2QR, UK. robert.carling@virgin.net
Russell
Michael G N
MG
Moore
Kevin W
KW
Mitchinson
Andrew
A
Guiblin
Alexander
A
Smith
Alison
A
Wafford
Keith A
KA
Marshall
George
G
Atack
John R
JR
Street
Leslie J
LJ
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*
D058785:GABA-A Receptor Agonists; C546257:GABRA3 protein, human; D008024:Ligands; D011720:Pyrazoles; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D014227:Triazines