Imidazo-triazine derivatives as ligands for GABA receptors
AssigneeMerck Sharp & Dohme Corp.
InventorsWilliam Robert Carling, Alexander Richard Guiblin, Kevin William Moore, Christopher Richard Moyes, Michael Rowley, Leslie Joseph Street
Life of this patent
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Abstract
A class of substituted 1,2,4-triazolo[4,3-]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position, a substituted alkoxy moiety at the 6-position, and an optionally substituted bicycloalkyl ring system at the 7-position, are selective ligands for GABAA receptors, in particular having high affinity for the α2 and/or α3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.
Claims9
A compound of formula I, or a salt thereof:
- wherein
- Y represents hydrogen, C1-6 alkyl or C3-7 cycloalkyl;
- Z represents C1-6 alkyl, C3-7 cycloalkyl, C4-7 cycloalkenyl, C6-8 bicycloalkyl, aryl, C3-7 heterocycloalkyl, heteroaryl or di(C1-6)alkylamino, any of which groups may be optionally substituted;
- R1 represents C3-7 cycloalkyl, phenyl, furyl, thienyl or pyridinyl, any of which groups may be optionally substituted;
- and
- R2 represents C3-7 cycloalkyl(C1-6)alkyl, aryl(C1-6)alkyl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted.
A compound selected from:
- 3,8-diphenyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 8-(2-fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-phenyl-imidazo[1,2-d][1,2,4]triazine;
- 8-(2-fluorophenyl)-2-(1-methyl-1H-[1,2,4]triazol-3-ylmethoxy)-3-phenyl-imidazo[1,2-d][1,2,4]triazine;
- 8-(2,5-difluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-phenylimidazo[1,2-d][1,2,4]triazine;
- 8-(4-fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-phenyl-imidazo[1,2-d][1,2,4]triazine;
- 8-(2,6-difluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-phenylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclobutyl-8-(2-fluorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-imidazo[1,2-d][1,2,4]triazine;
- 3-(3-chlorophenyl)-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-phenyl-imidazo[1,2-d][1,2,4]triazine;
- 3-cyclobutyl-5-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-phenylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-5-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-phenylimidazo[1,2-d][1,2,4]triazine;
- 8-(2-fluorophenyl)-5-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-3-phenylimidazo[1,2-d][1,2,4]triazine;
- or a salt thereof.
A compound selected from:
- 3-cyclopentyl-5-ethyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-phenylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-5-ethyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-phenylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-5-cyclopropyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-phenylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-8-(2,6-difluorophenyl)-5-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3-cyclohexyl-8-(2-fluorophenyl)-5-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3,8-bis(2-fluorophenyl)-5-methyl-72-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-8-(2,6-difluorophenyl)-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-5-methylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-8-(2-fluorophenyl)-5-methyl-2-(3-methyl-3H-[1,2,3]triazol-4-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-8-(2-fluorophenyl)-5-methyl-2-(1-methyl-1H-[1,2,4]triazol-3-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-8-(2-fluorophenyl)-5-methyl-2-(1-methyl-1H-[1,2,3]triazol-4-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-(2-fluorophenyl)-5-methylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-8-(2-fluorophenyl)-5-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)imidazo[1,2-d][1,2,4]triazine;
- 3-cyclohexyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-8-(2-fluorophenyl)-5-methylimidazo[1,2-d][1,2,4]triazine;
- 3-cyclopentyl-2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-5-methyl-8-phenyl-imidazo[1,2-d][1,2,4]triazine;
- 2-(2-ethyl-2H-[1,2,4]triazol-3-ylmethoxy)-5-methyl-8-phenyl-3-(thien-2-yl)-imidazo[1,2-d][1,2,4]triazine;
- or a salt thereof.
Dependencies are inferred from the claim text.