- Discovery of imidazo[1,2-b][1,2,4]triazines as GABAA α2/3 subtype selective agonists for the treatment of anxiety
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The identification of a series of imidazo[1,2-b][1,2,4]triazines with high affinity and functional selectivity for the GABAA α3-containing receptor subtype is described, leading to the identification of a clinical candidate, 11. Compound 11 shows good bioavailability and half-life in preclinical species, and it is a nonsedating anxiolytic in both rat and squirrel monkey behavioral models.
- Russell, Michael G. N.,Carling, Robert W.,Street, Leslie J.,Hallett, David J.,Goodacre, Simon,Mezzogori, Elena,Reader, Michael,Cook, Susan M.,Bromidge, Frances A.,Newman, Robert,Smith, Alison J.,Wafford, Keith A.,Marshall, George R.,Reynolds, David S.,Dias, Rebecca,Ferris, Pushpindar,Stanley, Jo,Lincoln, Rachael,Tye, Spencer J.,Sheppard, Wayne F. A.,Sohal, Bindi,Pike, Andrew,Dominguez, Maria,Atack, John R.,Castro, José L.
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p. 1235 - 1238
(2007/10/03)
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- Palladium-catalyzed regioselective arylation of imidazo[1,2-b][1,2,4] triazine: Synthesis of an α2/3-selective GABA agonist
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A convergent, practical, and efficient synthesis of 2′,6-difluoro- 5′-[3-(1-hydroxy-1-methylethy)-imidazo[1,2-b][1,2,4]triazin-7-yl] biphenyl-2-carbonitrile (1), an orally active GABAA dag-selective agonist, is described. The seven-step, chromatography-fr
- Gauthier Jr., Donald R.,Limanto, John,Devine, Paul N.,Desmond, Richard A.,Szumigala Jr., Ronald H.,Foster, Bruce S.,Volante
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p. 5938 - 5945
(2007/10/03)
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- Facile Synthesis of 2-Bromo-3-fluorobenzonitrile: An Application and Study of the Halodeboronation of Aryl Boronic Acids
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A scaleable synthesis of 2-bromo-3-fluorobenzonitrile via the NaOMe-catalyzed bromodeboronation of 2-cyano-6-fluorophenylboronic acid was developed. The generality of this transformation was demonstrated through the halodeboronation of a series of aryl boronic acids. Both aryl bromides and aryl chlorides were formed in good to excellent yields when the corresponding aryl boronic acid was treated with 1,3-dihalo-5,5-dimethylhydantoin and 5 mol % NaOMe.
- Szumigala Jr., Ronald H.,Devine, Paul N.,Gauthier Jr., Donald R.,Volante
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p. 566 - 569
(2007/10/03)
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- IMIDAZO-PYRIDINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
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A class of 8-fluoro-3-phenylimidazo[1,2-a]pyridine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group, or by a pyrrolidinonyl group, which is directly attached or bridged by an oxygen atom or by a -NH- or -OCH2- linkage, being selective ligands for GABAA receptors, in particular having high affinity for the α2 and/or α3 and/or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
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- IMIDAZO-TRIAZINE DERIVATIVES AS LIGANDS FOR GABA RECEPTORS
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A class of 7-phenylimidazo[1,2-b][1,2,4]triazine derivatives, substituted at the meta position of the phenyl ring by an optionally substituted aryl or heteroaryl group which is directly attached or bridged by an oxygen atom or a -NH- linkage, and substituted on the phenyl ring by one or two further substituents as defined herein, being selective ligands for GABAA receptors, in particular having good affinity for the α2 and/or α3 and/or α5 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.
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Page/Page column 36-37
(2010/02/07)
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- Imidazo-triazine derivatives as ligands for GABA receptors
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A class of 7-phenylimidazo[1,2-b][1,2,4]triazine derivatives, substituted at the meta position of the phenyl ring by a (cyano)(fluoro)phenyl moiety, being selective ligands for GABAA receptors, in particular having good affinity for the α2 and/
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