2-carboxamide-7-piperazinyl-benzofuran derivatives

1. A compound of formula (I),

wherein

R 1 is pyridinyl or indolinyl, wherein said pyridinyl or indolinyl is optionally substituted with one or more substituents selected from the group consisting of C 1-4 alkyl, halogen, CF 3 , CN, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —NC 1-4 alkylC(O)C 1-4 alkyl, —NHC(O)C 1-4 alkyl, —C(O)HN(C 1-4 alkyl) and —C(O)N(C 1-4 alkyl) 2 ;

R 2 is C 1-4 alkyl, heterocyclyl, —C 1-4 alkyl-phenyl, —C 1-4 alkylheteroaryl, carbocyclyl, —C 1-4 alkylheterocyclyl, -heterocyclyl-heteroaryl, -phenyl-heterocyclyl, -carbocyclyl-heteroaryl, -heterocyclyl-phenyl, wherein in said groups the heterocyclyl, phenyl, heteroaryl or carbocyclyl moiety may be optionally substituted with one or more substituents selected from the group consisting of halogen, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C 0-4 alkylSO 2 C 1-4 alkyl, cyano, hydroxy, and —C 1-4 alkyl;

R 3 is hydrogen or C 1-4 alkyl, or

R 2 and R 3 may together with the nitrogen atom, form a saturated ring system containing 4, 5 or 6 ring forming atoms selected from carbon or nitrogen and wherein said ring system is optionally substituted with one or more substituent selected from halogen, C 1-4 alkyl and C 1-4 alkoxy, —O-heteroaryl;

R 4 is hydrogen, halogen, methyl or methoxy;

wherein

heteroaryl is a monocyclic aromatic heterocycle containing 1 or 2 heteroatoms that are each independently nitrogen, sulphur, or oxygen; or benzodioxolyl; and

heterocyclyl is a saturated monocyclic ring containing 3 to 7 atoms of which 1 or 2 ring atoms are each independently nitrogen, sulphur, or oxygen;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein R 1 is indolinyl.

3. The compound according to claim 1 , wherein R 1 is pyridinyl.

4. The compound according to claim 1 , wherein R 2 is —C 1-4 alkylheteroaryl and wherein said heteroaryl is pyridinyl, pyrimidinyl, imidazolyl, pyrazolyl or benzodioxolyl.

5. The compound according to claim 1 , wherein R 2 and R 3 are C 1-4 alkyl.

6. The compound of formula (I),

wherein

R 1 is pyridine-2-yl;

R 2 is C 1-4 alkyl, heterocyclyl, —C 1-4 alkyl-phenyl, —C 1-4 alkylheteroaryl, carbocyclyl, —C 1-4 alkylheterocyclyl, -heterocyclyl-heteroaryl, -phenyl-heterocyclyl, -carbocyclyl-heteroaryl, heterocyclyl-phenyl, or -heterocyclyl-O-heteroaryl, wherein said groups the heterocyclyl, phenyl, heteroaryl or carbocyclyl moiety may be optionally substituted with one or more substituents selected from the group consisting of halogen, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C 0-4 alkylSO 2 C 1-4 alkyl, cyano, hydroxy, and C 1-4 alkyl;

R 3 is hydrogen or C 1-4 alkyl, or

R 2 and R 3 may together with the nitrogen atom, form a saturated ring system containing 4 or 5 or 6 ring forming atoms selected from carbon or nitrogen;

R 4 is hydrogen,

wherein

heteroaryl is a monocyclic aromatic heterocycle containing 1 or 2 heteroatoms that are each independently nitrogen, sulphur, or oxygen; or benzodioxolyl; and

heterocyclyl is a saturated monocyclic ring containing 3 to 7 atoms of which 1 or 2 ring atoms are each independently nitrogen, sulphur, or oxygen;

or a pharmaceutically acceptable salt thereof.

7. The compound of formula (I) according to claim 1 , wherein

R 1 is pyridine-2-yl;

R 2 and R 3 are C 1-4 alkyl;

R 4 is hydrogen, or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 , which is

7-(4-(2-(Pyridin-2-yl)ethyl)piperazin-1-yl)-N-(pyridin-2-ylmethyl)benzofuran-2-carboxamide;

N-(4-Morpholinophenyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(1-Phenylpiperidin-4-yl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(4-(Methylsulfonyl)benzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-((1 -Methyl-1H-imidazol-4-yl)methyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1 -yl)benzofuran-2-carboxamide;

N-(1 -Acetylpiperidin-4-yl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(1-(Pyridin-2-yl)ethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(1-(3-Chloropyridin-2-yl)piperidin-4-yl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(4-Cyanobenzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(Benzo [d][1,3]dioxol5-ylmethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-Methyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-Cyclopropyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(3,3-Difluorocyclobutyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

Azetidin-1-yl(7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-yl)methanone;

(7-(4-(2-(Pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-yl)(pyrrolidin-1-yl)methanone;

N-(4-(Methylsulfonylmethyl)benzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(3-Methoxyphenethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-Methyl-N-(3-(methylsulfonyl)benzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-((6-Cyanopyridin-3-yl)methyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-Methyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)-N-(pyridin-3-ylmethyl)benzofuran-2-carboxamide;

N-(3 -Cyanobenzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin- 1 -yl)benzofuran-2-carboxamide;

(7-(4-(2-(Pyridin-2-yl)ethyl)piperazin- 1-yl)benzofuran-2-yl)(4-(thiazol-2-yl)piperazin- 1 1-yl)methanone;

N-(1-(3-Methoxypyridin-2-yl)piperidin-4-yl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-Methyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin- 1 -yl)-N-(pyridin-2-ylmethyl)benzofuran-2-carboxamide;

N-(3 -Methoxybenzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin- 1 -yl)benzofuran-2-carboxamide;

N-(1 -(Pyridin-2-yl)cyclopropyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1 -yl)benzofuran-2-carboxamide;

N-(4-Methoxybenzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin- 1-yl)benzofuran-2-carboxamide;

N-(2-(4-Methylpyrimidin-2-yl)ethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin- 1-yl)benzofuran-2-carboxamide;

N-(2-(1-Methyl-1H-imidazol-4-yl)ethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

7-(4-(2-(Pyridin-2-yl)ethyl)piperazin- 1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)benzofuran-2-carboxamide;

N-(1-(1-Methyl-1H-pyrazol-5-yl)ethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-(1-(6-Methylpyridin-3-yl)ethyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

N-((2-Methylpyrimidin-5-yl)methyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

7-(4-(2-(Pyridin-2-yl)ethyl)piperazin-1-yl)-N-(pyridin-3-ylmethyl)benzofuran-2-carboxamide;

(7-(4-(2-(Pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-yl)(3-(pyridin-3-yloxy)azetidin-1-yl)methanone;

N-(3-Hydroxybenzyl)-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

7-(4-(2-(4-Methoxypyridin-2-yl)ethyl)piperazin-1-yl)—N,N-dimethylbenzofuran-2-carboxamide;

N,N-dimethyl-7-(4-(2-(5-methylpyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

7-(4-(2-(4-Cyanopyridin-2-yl)ethyl)piperazin-1-yl)—N,N-dimethylbenzofuran-2-carboxamide;

N,N-Dimethyl-7-(4-(2-(6-(trifluoromethyl)pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide;

7-(4-(2-(5-Acetylpyridin-2-yl)ethyl)piperazin-1-yl)-N,N-dimethylbenzofuran-2-carboxamide;

7-(4-(2-(5-Acetamidopyridin-2-yl)ethyl)piperazin-1-yl)-N,N-dimethylbenzofuran-2-carboxamide;

Azetidin-1-yl(7-(4-(2-(6-methoxypyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-yl)methanone;

7-(4-(2-(6-Methoxypyridin-2-yl)ethyl)piperazin-1-yl)-N,N-dimethylbenzofuran-2-carboxamide;

7-(4-(2-(5-Fluoropyridin-2-yl)ethyl)piperazin-1-yl)-N,N-dimethylbenzofuran-2-carboxamide;

7-(4-(2-(3-Methoxy-2-pyridyl)ethyl)piperazin-1-yl)-N,N-dimethylbenzofuran-2-carboxamide;

1-(5-(2-(4-(2-(Azetidine-1-carbonyl)benzofuran-7-yl)piperazin-1-yl)ethyl)indolin-1-yl)ethanone;

5-Fluoro-N,N-dimethyl-7-(4-(2-pyridin-2-yl)piperazin-1-yl)benzofuran-2-carboxamide;

7-(4-(2-(1-Acetylindolin-5-yl)ethyl)piperazin- 1-yl)-5 -fluoro-N,N-dimethylbenzofuran-2-carboxamide;

5-Methoxy-N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide and

4-Bromo-N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl)benzofuran-2-carboxamide; or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising as active ingredient a therapeutically effective amount of a compound of formula (I) according to claim 1 in association with a pharmaceutically acceptable excipient, carrier or diluent.

10. A method of treating bipolar depression or Major Depressive Disorders (MDD) comprising administering to a patient in need of such a treatment, a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in claim 1 .

11. A method of treating depression or major depression comprising administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in claim 1 .