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.
MeSH terms
-
Animals
-
Anti-Anxiety Agents / administration & dosage
-
Anti-Anxiety Agents / chemical synthesis
-
Anti-Anxiety Agents / pharmacology*
-
Anxiety / drug therapy*
-
Binding Sites
-
GABA Agonists / administration & dosage
-
GABA Agonists / chemical synthesis
-
GABA Agonists / pharmacology*
-
GABA-A Receptor Agonists*
-
Humans
-
Ligands
-
Molecular Structure
-
Pyridazines / administration & dosage
-
Pyridazines / chemical synthesis
-
Pyridazines / pharmacology*
-
Rats
-
Recombinant Proteins / agonists
-
Stereoisomerism
-
Structure-Activity Relationship
Substances
-
Anti-Anxiety Agents
-
GABA Agonists
-
GABA-A Receptor Agonists
-
Ligands
-
Pyridazines
-
Recombinant Proteins