Diphenylpyridine derivatives, preparation and therapeutic application thereof

A pharmaceutical composition comprising a compound of formula (I), including in the form of a base or an addition salt with an acid, or a hydrate or a solvate thereof, in combination with at least one pharmaceutically acceptable excipient:

• in which:
• R1 represents hydrogen or a (C1-C4)alkyl;
• R2 represents:
• a saturated mononitrogenous heterocyclic radical containing from 5 to 7 atoms, the nitrogen atom being substituted with an alkanoyl group;
• a group NR10R11;
• a nonaromatic C3-C10 carbocyclic radical which is substituted more than 3 times with a (C1-C4)alkyl group;
• a nonaromatic C11-C12 carbocyclic radical which is unsubstituted or substituted one or more times with a (C1-C4)alkyl group;
• a saturated monooxygenated heterocyclic radical containing from 5 to 7 atoms, which is substituted more than 3 times with a (C1-C4)alkyl group;
• or R1 and R2, together with the nitrogen atom to which they are attached, constitute a piperidin-1-yl radical disubstituted in the 4-position with a phenyl or benzyl group and with a (C1-C4)alkyl, (C1-C4)alkoxy, cyano, aminocarbonyl, (C1-C4)alkyl-aminocarbonyl, di(C1-C4)alkylaminocarbonyl, (C1-C3)-alkanoyl or (C1-C3)alkanoylamino group;
• the phenyl or benzyl groups substituting the piperidin-1-yl radical being unsubstituted or substituted with a halogen atom and/or a methyl and/or trifluoromethyl group;
• R3, R4, R5, R6, R7 and R8 each represent, independently of one another, a hydrogen or halogen atom, or a (C1-C6)alkyl, (C1-C6)alkoxy or trifluoromethyl group;
• R9 represents a hydrogen atom, a (C1-C4)alkyl or cyano group or a CH2OH, CH2CN or CH2O(C1-C4)alkyl group;
• R10 and R11, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical containing from 7 to 10 atoms, possibly containing a second hetero atom chosen from O and N, the said radical being unsubstituted or substituted one or more times with a (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy or methoxy(C1-C2)alkylene group, or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane;
• or R10 and R11, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical containing 5 or 6 atoms, containing a second nitrogen atom, the said radical being substituted one or more times with a methoxy(C1-C2)alkylene group, or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane;
• or R10 and R11, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical containing 5 or 6 atoms, optionally containing an oxygen atom, the said radical being substituted one or more times with a (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy or methoxy(C1-C2)alkylene group, or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane.

A method of treatment of a disease selected from the group consisting of appetite disorder, gastrointestinal disorder, inflammatory phenomena, immune system disease, psychotic disorder, alcohol addiction and nicotine addiction in a patient comprising administering to said patient a therapeutically effective amount of a compound of formula (I), including in the form of a base or an addition salt with an acid, or a hydrate or a solvate thereof:

• in which:
• R1 represents hydrogen or a (C1-C4)alkyl;
• R2 represents:
• a saturated mononitrogenous heterocyclic radical containing from 5 to 7 atoms, the nitrogen atom being substituted with an alkanoyl group;
• a group NR10R11;
• a nonaromatic C3-C10 carbocyclic radical which is substituted more than 3 times with a (C1-C4)alkyl group;
• a nonaromatic C11-C12 carbocyclic radical which is unsubstituted or substituted one or more times with a (C1-C4)alkyl group;
• a saturated monooxygenated heterocyclic radical containing from 5 to 7 atoms, which is substituted more than 3 times with a (C1-C4)alkyl group;
• or R1 and R2, together with the nitrogen atom to which they are attached, constitute a piperidin-1-yl radical disubstituted in the 4-position with a phenyl or benzyl group and with a (C1-C4)alkyl, (C1-C4)alkoxy, cyano, aminocarbonyl, (C1-C4)alkylaminocarbonyl, di(C1-C4)alkylaminocarbonyl, (C1-C3)-alkanoyl or (C1-C3)alkanoylamino group;
• the phenyl or benzyl groups substituting the piperidin-1-yl radical being unsubstituted or substituted with a halogen atom and/or a methyl and/or trifluoromethyl group;
• R3, R4, R5, R6, R7 and R8 each represent, independently of one another, a hydrogen or halogen atom, or a (C1-C6)alkyl, (C1-C6)alkoxy or trifluoromethyl group;
• R9 represents a hydrogen atom, a (C1-C4)alkyl or cyano group or a CH2OH, CH2CN or CH2O(C1-C4)alkyl group;
• R10 and R11, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical containing from 7 to 10 atoms, possibly containing a second hetero atom chosen from O and N, the said radical being unsubstituted or substituted one or more times with a (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy or methoxy(C1-C2)alkylene group, or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane;
• or R10 and R11, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical containing 5 or 6 atoms, containing a second nitrogen atom, the said radical being substituted one or more times with a methoxy(C1-C2)alkylene group, or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane;
• or R10 and R11, together with the nitrogen atom to which they are attached, constitute a saturated or unsaturated heterocyclic radical containing 5 or 6 atoms, optionally containing an oxygen atom, the said radical being substituted one or more times with a (C1-C4)alkyl, hydroxyl, (C1-C4)alkoxy or methoxy(C1-C2)alkylene group, or substituted with a spirocyclobutane, a spirocyclopentane or a spirocyclohexane.