Abstract
The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABA(A) alpha3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models.
MeSH terms
-
Animals
-
Anti-Anxiety Agents / chemical synthesis*
-
Anti-Anxiety Agents / chemistry
-
Anti-Anxiety Agents / pharmacology
-
Biological Availability
-
GABA-A Receptor Agonists*
-
Half-Life
-
Humans
-
Imidazoles / chemical synthesis*
-
Imidazoles / chemistry
-
Imidazoles / pharmacology
-
Patch-Clamp Techniques
-
Radioligand Assay
-
Rats
-
Receptors, GABA-A / physiology
-
Saimiri
-
Structure-Activity Relationship
-
Triazines / chemical synthesis*
-
Triazines / chemistry
-
Triazines / pharmacology
Substances
-
Anti-Anxiety Agents
-
GABA-A Receptor Agonists
-
GABRA2 protein, human
-
GABRA3 protein, human
-
Gabra3 protein, rat
-
Imidazoles
-
Receptors, GABA-A
-
Triazines