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 |
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| container_end_page | 2610 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 49 |
| creator | 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 |
| description | 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. |
| format | Article |
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| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2006-04, Vol.49 (8), p.2600-2610 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | 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 |
| title | A pyridazine series of alpha2/alpha3 subtype selective GABA A agonists for the treatment of anxiety |
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