Azabicyclo (3.1.0) hexane derivatives useful as modulators of dopamine D3 receptors
AssigneeGlaxo Group Limited
InventorsAnna Maria Capelli, Giovanna Tedesco
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AssigneeGlaxo Group Limited
InventorsAnna Maria Capelli, Giovanna Tedesco
Estimating the term…
The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl; or corresponds to a group R5; R2 is hydrogen or C1-4alkyl; R3 is C1-4alkyl; R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; R5 is a moiety selected from the group consisting of: isoxazolyl, —CH2—N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; and when R1 is chlorine and p is 1, such R1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R1 corresponds to R5, p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, e.g. to treat drug dependency or as antipsychotic agents.
A composition of matter comprising 3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane, a stereoisomer thereof, or a salt thereof.
A method of treating substance abuse comprising administering an effective amount of 3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane, or (1S,5R)-3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)-phenyl]-3-azabicyclo[3.1.0]hexane, or a mixture of 3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane, or (1S,5R)-3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)-phenyl]-3-azabicyclo[3.1.0]hexane, neat or admixed with a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising 3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane, or (1S,5R)-3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)-phenyl]-3-azabicyclo[3.1.0]hexane, or a mixture of 3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane, or (1S,5R)-3-(3-{[4-methyl-5-(4-pyridazinyl)-4H-1,2,4-triazol-3-yl]thio}propyl)-1-[4-(trifluoromethyl)-phenyl]-3-azabicyclo[3.1.0]hexane, or a pharmaceutically acceptable salt thereof;
Dependencies are inferred from the claim text.