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US 6,319,924 B1Granted
Triazolo-pyridazine derivatives as ligands for GABA receptors
AssigneeMerck Sharp & Dohme Corp.
InventorsTimothy Harrison, Timothy Jason Sparey
Life of this patent
Estimating the term…
Abstract
1,2,4-triazolo[4,3-b]pyridazine derivatives, represented by wherein Z represents an optionally substituted tetrahydropyridinyl substituent, are selective ligands for GABAA receptors, in particular having high affinity for the α2 and/or α3 subunit thereof, are useful in the treatment of anxiety and convulsions.
Claims8
A compound of formula I, or a salt thereof:
- wherein
- Y represents hydrogen or C1-6alkyl;
- Z represents a tetrahydropyridinyl moiety optionally substituted with one or two independent C1-6alkyl, aryl(C1-6)alkyl, pyridyl(C1-6)alkyl, halogen, halo(C1-6)alkyl, cyano, cyano(C1-6)alkyl, hydroxy, hydroxymethyl, C1-6alkoxy, C3-7cycloalkyl(C1-6)alkoxy, C3-7cycloalkoxy, amino(C1-6)alkyl, di(C1-6)alkylamino(C1-6)alkyl, di(C1-6)alkylaminocarbonyl(C1-6)alkyl, N-(C1-6)alkylpiperidinyl, pyrrolidinyl(C1-6)alkyl, piperazinyl(C1-6)alkyl, morpholinyl(C1-6)alkyl, di(C1-6)alkylmorpholinyl(C1-6)alkyl or imidazolyl(C1-6)alkyl;
- R1 represents C3-7cycloalkyl, phenyl, furyl, thienyl or pyridinyl, any of which groups may be optionally substituted with one or two independent C1-6alkyl, aryl(C1-6)alkyl, pyridyl(C1-6)alkyl, halogen, halo(C1-6)alkyl, cyano, cyano(C1-6)alkyl, hydroxy, hydroxymethyl, C1-6alkoxy, C3-7cycloalkyl(C1-6)alkoxy, C3-7cycloalkoxy, amino(C1-6)alkyl, di(C1-6)alkylamino(C1-6)alkyl, di(C1-6)alkylaminocarbonyl(C1-6)alkyl, N-(C1-6)alkylpiperidinyl, pyrrolidinyl(C1-6)alkyl, piperazinyl(C1-6)alkyl, morpholinyl(C1-6)alkyl, di(C1-6)alkylmorpholinyl(C1-6)alkyl or imidazolyl(C1-6)alkyl;
- and
- R2 represents cyano(C1-6)alkyl, hydroxy(C1-6)alkyl, C3-7cycloalkyl(C1-6)alkyl, propargyl, C3-7heterocycloalkylcarbonyl(C1-6)alkyl, aryl(C1-6)alkyl or heteroaryl(C1-6)alkyl, any of which groups may be optionally substituted with one or two independent C1-6alkyl, aryl(C1-6)alkyl, pyridyl(C1-6)alkyl, halogen, halo(C1-6)alkyl, cyano, cyano(C1-6)alkyl, hydroxy, hydroxymethyl, C1-6alkoxy, C3-7cycloalkyl(C1-6)alkoxy, C3-7cycloalkoxy, amino(C1-6)alkyl, di(C1-6)alkylamino(C1-6)alkyl, di(C1-6)alkylaminocarbonyl(C1-6)alkyl, N-(C1-6)alkylpiperidinyl, pyrrolidinyl(C1-6)alkyl, piperazinyl(C1-6)alkyl, morpholinyl(C1-6)alkyl, di(C1-6)alkylmorpholinyl(C1-6)alkyl or imidazolyl(C1-6)alkyl, wherein aryl represents phenyl or naphthyl, wherein heteroaryl represents pyridinyl, quinolinyl, isoquinolinyl, pyridazinyl, pyrimidinyl, pyrazinyl, quinoxalinyl, furyl, benzofuryl, dibenzofuryl, thienyl, benzthienyl, pyrrolyl, indolyl, pyrazolyl, indazolyl, oxazolyl, isoxazolyl, thiazoyl, isothiazolyl, imidazolyl, benzimidazolyl, oxadiazolyl, thiadiazolyl, triazolyl, or tetrazolyl, and wherein heterocycloalkyl represents azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl or thiomorpholinyl.
3 more elements
A compound selected from:
- 7-(3,6-dihydro-2H-pyridin-1-yl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine;
- 7-(3,6-dihydro-2H-pyridin-1-yl)-6-(1-methyl-1H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine;
- 3-(2,4-difluorophenyl)-7-(3,6-dihydro-2H-pyridin-1-yl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine;
- 7-(3,6-dihydro-2H-pyridin-1-yl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(pyridin-3-yl)-1,2,4-triazolo[4,3-b]pyridazine;
- 7-(3,6-dihydro-2H-pyridin-1-yl)-6-(3-methylpyridin-2-ylmethoxy)-3-(pyridin-3-yl)-1,2,4-triazolo[4,3-b]pyridazine;
- and salts thereof.
3 more elements
Dependencies are inferred from the claim text.