Piperidinylpyrazolopyridine derivative

1. A compound represented by the general formula (I) or a pharmacologically acceptable salt thereof:

wherein R represents an optionally substituted aryl group (the substituent(s) is 1 to 3 identical or different groups selected from the group consisting of a halogen atom, a C 1-6 alkyl group, a C 3-7 cycloalkyl group, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group, a C 1-6 alkoxy group, a C 3-7 cycloalkoxy group, a phenyl group, a C 2-7 alkoxycarbonyl group, a benzyloxycarbonyl group, a di(C 1-6 alkyl)aminocarbonyl group, and a di(C 1-6 alkyl)amino group) or an optionally substituted heteroaryl group (the heteroaryl is a 5- or 6-membered ring which is optionally further condensed with a benzene ring; the heteroatom(s) on the ring of the heteroaryl group is 1 or 2 nitrogen atoms, and the ring optionally further contains one nitrogen atom, oxygen atom, or sulfur atom; the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a halogen atom, a C 1-6 alkyl group, a C 3-7 cycloalkyl group, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group, a C 1-6 alkoxy group, a C 3-7 cycloalkoxy group, a phenyl group, a C 2-7 alkoxycarbonyl group, a benzyloxycarbonyl group, a di(C 1-6 alkyl)aminocarbonyl group, and a di(C 1-6 alkyl)amino group; and the heteroaryl group is optionally further substituted by one optionally substituted heteroaryl group (the heteroaryl is a 5- or 6-membered ring which is optionally further condensed with a benzene ring; the heteroatom(s) on the ring of the heteroaryl group is 1 or 2 nitrogen atoms, and the ring optionally further contains one nitrogen atom, oxygen atom, or sulfur atom; and the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a halogen atom, a C 1-6 alkyl group, a trifluoromethyl group, a cyano group, and a C 1-6 alkoxy group)).

2. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R is a substituted aryl group (the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a chlorine atom, a fluorine atom, a C 1-3 alkyl group, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group, and a C 1-3 alkoxy group).

3. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R is a substituted phenyl group (the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a chlorine atom, a difluoromethoxy group, a trifluoromethoxy group, and a cyano group).

4. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R is a substituted phenyl group (the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a difluoromethoxy group, a trifluoromethoxy group, and a cyano group).

5. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R is a substituted heteroaryl group (the heteroaryl is a 5- or 6-membered ring; the heteroatom on the ring of the heteroaryl group is one nitrogen atom, and the ring optionally further contains one nitrogen atom, oxygen atom, or sulfur atom; the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a halogen atom, a C 1-3 alkyl group, a C 3-6 cycloalkyl group, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group, a C 1-3 alkoxy group, a C 2-4 alkoxycarbonyl group, and a benzyloxycarbonyl group; and the heteroaryl group is optionally further substituted by one substituted heteroaryl group (the heteroaryl is 5- or 6-membered ring; the heteroatom on the ring of the heteroaryl group is one nitrogen atom, and the ring optionally further contains one nitrogen atom, oxygen atom, or sulfur atom; and the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a halogen atom, a C 1-3 alkyl group, a trifluoromethyl group, a cyano group, and a C 1-3 alkoxy group)).

6. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R is a substituted pyridyl, pyrimidyl, pyrazyl, pyridazyl, oxazolyl, or thiazolyl group (the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a chlorine atom, a fluorine atom, a C 1-3 alkyl group, a cyclopropyl group, a trifluoromethyl group, a difluoromethoxy group, a trifluoromethoxy group, a cyano group, a C 1-3 alkoxy group, a C 2-4 alkoxycarbonyl group, and a benzyloxycarbonyl group, and the pyridyl, pyrimidyl, pyrazyl, pyridazyl, oxazolyl, or thiazolyl group is optionally further substituted by one substituted thiazolyl group (the substituent(s) is a chlorine atom, a fluorine atom, a C 1-3 alkyl group, a trifluoromethyl group, a cyano group, or a C 1-3 alkoxy group)).

7. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein R is a substituted pyridyl group (the substituent(s) is 1 or 2 identical or different groups selected from the group consisting of a chlorine atom, a trifluoromethyl group, a difluoromethoxy group, and a trifluoromethoxy group).

8. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein the compound is selected from the group consisting of:

4-hydroxy-4-(trifluoromethyl)-3-{1-[6-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

4-hydroxy-4-(trifluoromethyl)-3-{1-[5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

3-[1-(5-chloropyridin-2-yl)piperidin-4-yl]-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

4-hydroxy-3-{1-[6-(propan-2-yloxy)pyridazin-3-yl]piperidin-4-yl}-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

2-{4-[4-hydroxy-6-oxo-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-3-yl]piperidin-1-yl}pyridine-4-carbonitrile;

5-{4-[4-hydroxy-6-oxo-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-3-yl]piperidin-1-yl}pyridine-3-carbonitrile;

4-hydroxy-4-(trifluoromethyl)-3-{1-[6-(trifluoromethyl)pyridin-3-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

4-hydroxy-4-(trifluoromethyl)-3-{1-[5-(trifluoromethyl)pyrazin-2-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

3-{1-[4,4′-bis(trifluoromethyl)-2,5′-bi-1,3-thiazol-2′-yl]piperidin-4-yl}-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

3-{1-[5-(difluoromethoxy)pyridin-2-yl]piperidin-4-yl}-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

4-hydroxy-3-{1-[5-(propan-2-yloxy)pyridin-2-yl]piperidin-4-yl}-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

3-{1-[6-(difluoromethoxy)pyridin-3-yl]piperidin-4-yl}-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

3-{1-[4-(difluoromethoxy)phenyl]piperidin-4-yl}-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

5-{4-[4-hydroxy-6-oxo-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-3-yl]piperidin-1-yl}-2-(trifluoromethoxy)benzonitrile;

4-hydroxy-4-(trifluoromethyl)-3-{1-[2-(trifluoromethyl)pyrimidin-5-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

4-hydroxy-3-{1-[5-(trifluoromethoxy)pyridin-2-yl]piperidin-4-yl}-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

benzyl 2-[4-(4-hydroxy-6-oxo-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-1-yl]-5-(trifluoromethyl)pyridine-4-carboxylate;

4-hydroxy-3-{1-[2-(propan-2-yl)-6-(trifluoromethyl)pyrimidin-4-yl]piperidin-4-yl}-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

ethyl 2-{4-[4-hydroxy-6-oxo-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-3-yl]piperidin-1-yl}-4-(trifluoromethyl)-1,3-oxazole-5-carboxylate;

6-{4-[4-hydroxy-6-oxo-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-b]pyridin-3-yl]piperidin-1-yl}-4-(trifluoromethyl)pyridine-3-carbonitrile; and

3-[1-(5-cyclopropylpyridin-2-yl)piperidin-4-yl]-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one.

9. The compound according to claim 1 or a pharmacologically acceptable salt thereof, wherein the compound is selected from the group consisting of:

(−)-4-hydroxy-4-(trifluoromethyl)-3-{1-[5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one;

(−)-3-[1-(5-chloropyridin-2-yl)piperidin-4-yl]-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one; and

(−)-3-{1-[4-(difluoromethoxy)phenyl]piperidin-4-yl}-4-hydroxy-4-(trifluoromethyl)-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-b]pyridin-6-one.

10. A pharmaceutical composition comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof as an active ingredient.

11. A pharmaceutical composition comprising a compound according to claim 1 or a pharmacologically acceptable salt thereof and a pharmacologically acceptable carrier.

12. A method for making a pharmaceutical composition, comprising combining a pharmacologically acceptable carrier with a compound according to claim 1 or a pharmacologically acceptable salt thereof.