A pyridazine series of alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety

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...

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Veröffentlicht in:	Journal of medicinal chemistry 2006-04, Vol.49 (8), p.2600-2610
Hauptverfasser:	Lewis, Richard T, Blackaby, Wesley P, Blackburn, Timothy, Jennings, Andrew S R, Pike, Andrew, Wilson, Rowan A, Hallett, David J, Cook, Susan M, Ferris, Pushpinder, Marshall, George R, Reynolds, David S, Sheppard, Wayne F A, Smith, Alison J, Sohal, Bindi, Stanley, Joanna, Tye, Spencer J, Wafford, Keith A, Atack, John R
Format:	Artikel
Sprache:	eng
Schlagworte:	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
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Zusammenfassung:	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.
ISSN:	0022-2623