Imidazo-triazine derivatives as ligands for GABA receptors
AssigneeMerck Sharp & Dohme Corp.
InventorsWilliam Robert Carling, David James Hallett, Michael Geoffrey Neil Russell, Leslie Joseph Street
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Abstract
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/or α3 subunit thereof, are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety and convulsions.
Claims13
A compound of formula I, or a pharmaceutically acceptable salt thereof:
- wherein
- X1 represents hydrogen or fluoro;
- R11 represents hydrogen, (C1-6 alkyl, halo(C1-6)alkyl, dihalo(C1-6)alkyl, hydroxy(C1-6)alkyl, halogen, trifluoromethyl, C1-6 alkoxy, formyl, (C2-6 alkylcarbonyl, (C2-6 alkoxycarbonyl or —CR4═NOR5, or a heteroaryl selected from the group consisting of:
- pyridinyl, quinolinyl, isoquinolinyl, pyridazinyl, pyrimidinyl, pyrazinyl, furyl, benzofuryl, dibenzofuryl, thienyl, benzthienyl, pyrrolyl, indolyl, pyrazolyl, indazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, triazolyl and tetrazolyl;
- R4 represents hydrogen or C1-6 alkyl;
- R5 represents hydrogen, C1-6 alkyl, hydroxy(C1-6)alkyl or di(C1-6)alkylamino(C1-6)alkyl;
- and
- R6 represents fluoro.
A compound selected from:
- 4,2′-difluoro-5′-[3-(1-fluoro-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7yl]biphenyl-2-carbonitrile;
- 5,2′-difluoro-5′-(3-trifluoromethylimidazo[1,2-b][1,2,4]triazin-7-yl)-biphenyl-2-carbonitrile;
- 4,2′-difluoro-5′-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7yl]biphenyl-2-carbonitrile;
- 4-fluoro-3′-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]-biphenyl-2-carbonitrile;
- 6,2′-difluoro-5′-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile;
- and pharmaceutically acceptable salts thereof.
6,2′-Difluoro-5′-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile, or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition comprising an effective amount of 6,2′-difluoro-5′-[3-(1-hydroxy-1-methylethyl)imidazo1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile, or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable carrier.
A compound which is 6,2'-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile.
A method for the treatment of anxiety which comprises administering to a patient in need thereof an effective amount of 6,2'-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile or a pharmaceutically acceptable salt thereof.
A method for the prevention of anxiety which comprises administering to a patient in need thereof an effective amount of 6,2'-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.