Azabicyclo [3.1.0] Hexane Derivatives as Modulators of Dopamine D3 Receptors

Compound of formula (I)′ or a salt thereof:

• wherein
• G is selected from the group consisting of:
• phenyl, a 5- or 6-membered monocyclic heteroaryl group, or a 8- to 11-membered heteroaryl bicyclic group;
• p is an integer ranging from 0 to 5;
• R1 is halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5;
• or corresponds to a group R8;
• and when p is an integer ranging from 2 to 5, each R1 may be the same or different;
• R2 is hydrogen or C1-4alkyl;
• n is 3, 4, 5 or 6;
• R3 is selected from the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of:
• halogen, cyano, C1-4alkyl, C1-4alkoxy, C1-4alkanoyl and SF5;
• R4 is selected in the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R5 is selected in the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R6 is selected in the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R7 is hydrogen or C1-2alkyl;
• R8 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 R8 group is optionally substituted by one or two substituents selected from:
• halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl;
• R′ is H, C1-4 alkyl or C1-4 alkanoyl;
• R″ is defined as R′;
• R′ and R″ taken together with the interconnecting nitrogen atom may form a 5-, 6- membered saturated or unsaturated heterocyclic ring;
• wherein at least one of R3, R4, R6 and R5 is hydrogen;
• and wherein only one R2 group may be different from hydrogen.

A compound of formula (IA)

• wherein
• G is selected from the group consisting of:
• phenyl, a 5- or 6-membered monocyclic heteroaryl group, or a 8- to 11-membered heteroaryl bicyclic group;
• p is an integer ranging from 0 to 5;
• R1 is halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5;
• or corresponds to a group R8;
• and when p is an integer ranging from 2 to 5, each R1 may be the same or different;
• R2 is hydrogen or C1-4alkyl;
• n is 3, 4, 5 or 6;
• R3 is selected from the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R4 is selected in the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R5 is selected in the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R6 is selected in the group consisting of:
• hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR′R″;
• or R3 is a phenyl group, a 5-14 membered heterocyclic group;
• and any of such phenyl or heterocyclic group 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 and SF5;
• R7 is hydrogen or C1-2alkyl;
• R8 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 R8 group is optionally substituted by one or two substituents selected from:
• halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl;
• R′ is H, C1-4 alkyl or C1-4 alkanoyl;
• R″ is defined as R′;
• R′ and R″ taken together with the interconnecting nitrogen atom may form a 5-, 6- membered saturated or unsaturated heterocyclic ring;
• wherein at least one of R3, R4, R6 and R5 is hydrogen;
• and wherein only one R2 group may be different from hydrogen.
• or salts thereof.

A compound to claim 2 selected from the group consisting of:

• 6′-methyl-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-3,3′-bipyridin-2(1H)-one;
• 2′-fluoro-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-3,4′-bipyridin-2(1H)-one;
• 2′-fluoro-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-3,3′-bipyridin-2(1H)-one;
• 6′-fluoro-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-3,3′-bipyridin-2(1H)-one;
• 3-(5-pyrimidinyl)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1H)-pyridinone;
• 3-(methyloxy)-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1H)-pyridinone;
• 2-oxo-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-1,2-dihydro-3-pyridinecarbonitrile;
• 3-methyl-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1H)-pyridinone;
• 4-methyl-1-(4-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}butyl)-2(1H)-pyridinone;
• 3-methyl-1-(3-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-2(1H)-pyridinone;
• and salts thereof.