| 7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine: a functionally selective gamma-aminobutyric acid(A) (GABA(A)) alpha2/alpha3-subtype selective agonist that exhibits potent anxiolytic activity but is not sedating in animal models. | |
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MedLine Citation:
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PMID: 16279764 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There is increasing evidence that compounds with selectivity for gamma-aminobutyric acid(A) (GABA(A)) alpha2- and/or alpha3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABA(A) alpha2/alpha3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays. |
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Authors:
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Robert W Carling; Andrew Madin; Alec Guiblin; Michael G N Russell; Kevin W Moore; Andrew Mitchinson; Bindi Sohal; Andrew Pike; Susan M Cook; Ian C Ragan; Ruth M McKernan; Kathleen Quirk; Pushpinder Ferris; George Marshall; Sally Ann Thompson; Keith A Wafford; Gerard R Dawson; John R Atack; Timothy Harrison; José L Castro; Leslie J Street |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of medicinal chemistry Volume: 48 ISSN: 0022-2623 ISO Abbreviation: J. Med. Chem. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-11-10 Completed Date: 2006-01-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9716531 Medline TA: J Med Chem Country: United States |
Other Details:
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Languages: eng Pagination: 7089-92 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. robert_carling@merck.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Anxiety Agents / chemical synthesis*, chemistry, pharmacology Binding, Competitive Cell Line Dogs Half-Life Humans Hypnotics and Sedatives / chemical synthesis*, chemistry, pharmacology Mice Oocytes / drug effects, physiology Patch-Clamp Techniques Primates Pyridazines / chemical synthesis*, chemistry, pharmacology Radioligand Assay Rats Receptors, GABA-A / agonists*, antagonists & inhibitors, physiology Recombinant Proteins / agonists Structure-Activity Relationship Triazoles / chemical synthesis*, chemistry, pharmacology Xenopus |
| Chemical | |
Reg. No./Substance:
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0/7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo(4,3-b)pyridazine; 0/Anti-Anxiety Agents; 0/GABRA2 protein, human; 0/Hypnotics and Sedatives; 0/Pyridazines; 0/Receptors, GABA-A; 0/Recombinant Proteins; 0/Triazoles; 0/alpha1 subunit, GABA-A receptor; 0/alpha3 subunit, GABA-A receptor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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