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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 γ-Aminobutyric AcidA (GABAA) α2/α3-Subtype Selective Agonist That Exhibits Potent Anxiolytic Activity but Is Not Sedating in Animal Models

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Departments of Medicinal Chemistry, Biochemistry, and Pharmacology, Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, U.K.
Cite this: J. Med. Chem. 2005, 48, 23, 7089–7092
Publication Date (Web):October 14, 2005
Copyright © 2005 American Chemical Society

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    There is increasing evidence that compounds with selectivity for γ-aminobutyric acidA (GABAA) α2- and/or α3-subtypes may retain the desirable anxiolytic activity of nonselective benzodiazepines but possess an improved side effect profile. Herein we describe a novel series of GABAA α2/α3 subtype-selective agonists leading to the identification of the development candidate 17, a nonsedating anxiolytic in preclinical animal assays.


     To whom correspondence should be addressed. For R. C.:  phone, (+1279) 440000; fax, (+1279) 440187; e-mail, [email protected]. For J.L.C.:  phone, (+1279) 440000; fax, (+1279) 440187; e-mail, [email protected]. For L.J.S.:  phone, (+1279) 440000; fax, (+1279) 440187; e-mail, [email protected].

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