Imidazo[1,2-b][1,2,4]triazines as alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety.
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.
Jennings
Andrew S R
AS
Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. andrew_jennings@merck.com
Lewis
Richard T
RT
Russell
Michael G N
MG
Hallett
David J
DJ
Street
Leslie J
LJ
Castro
José L
JL
Atack
John R
JR
Cook
Susan M
SM
Lincoln
Rachael
R
Stanley
Joanna
J
Smith
Alison J
AJ
Reynolds
David S
DS
Sohal
Bindi
B
Pike
Andrew
A
Marshall
George R
GR
Wafford
Keith A
KA
Sheppard
Wayne F A
WF
Tye
Spencer J
SJ
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*
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