Pyrazol derivatives

1. A Compound of formula (I)

wherein

is a non-aromatic mono-cyclic radical of four to eight ring atoms, in which one or two ring atoms are nitrogen atoms, with the remaining ring atoms being carbon atoms;

provided that, when

contains the second ring nitrogen atom, said ring nitrogen atom is not directly bonded to another heteroatom or to a carbonyl group;

X is—

Y is phenyl, and said phenyl is substituted by one, two or three substituents independently selected from the group consisting of C 1-8 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyoxy, halogen, cyano, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted C 3-7 cycloalkyl, optionally substituted heterocyclyl, C 1-6 alkylvinyl, halo C 1-6 alkylvinyl, optionally substituted C 3-7 cycloalkylvinyl, optionally substituted heterocyclylvinyl, optionally substituted phenylvinyl, optionally substituted heteroarylvinyl, C 1-6 alkylethynyl, halo C 1-6 alkylethynyl, optionally substituted C 3-7 cycloalkylethynyl, optionally substituted heterocyclylethynyl, optionally substituted phenylethynyl, optionally substituted heteroarylethynyl, C 1-6 alkylcarbonylamino, halo C 1-6 alkyl carbonylamino, optionally substituted C 3-7 cycloalkylcarbonylamino, optionally substituted heterocyclylcarbonylamino, optionally substituted phenylcarbonylamino and optionally substituted heteroarylcarbonylamino;

R 1 , R 2 , R 3 and R 4 when attached to a ring carbon atom, independently are selected from the group consisting of hydrogen, C 1-6 alkyl, halo C 1-6 alkyl, heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy C 2-6 alkenyl, hydroxy C 2-6 alkynyl, C 1-6 alkoxy C 2-6 alkenyl, C 1-6 alkoxy C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, halo C 1-6 alkoxy, heteroalkoxy, halogen, optionally substituted phenyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 3-7 cycloalkyl C 1-6 alkyl, optionally substituted heteroaryl, optionally substituted phenyl-C 1-6 alkyl, optionally substituted heteroaryl-C 1-6 alkyl, optionally substituted heterocyclyl-C 1-6 alkyl, nitro, carboxy, formyl, acyl, C 1-6 alkoxycarbonyl, carbamoyl, mono- or di-C 1-6 alkyl substituted aminocarbonyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl or amino optionally substituted by one or two substituents independently selected from C 1-6 alkyl, acyl, heteroalkyl, optionally substituted C 3-7 cycloalkyl or optionally substituted heterocyclyl and optionally substituted heterocyclyl, in which one of the ring carbon atoms of the heterocyclyl may be a ring carbon atom of another ring which is C 3-7 cycloalkyl or heterocyclyl, one or two ring carbon atoms of said another ring being optionally replaced by a carbonyl group; and,

when two of R 1 , R 2 , R 3 and R 4 are attached to the same ring carbon atom, they can, together with the carbon atom to which they are attached, form a C 3-7 cycloalkyl ring or heterocyclyl ring; or

when attached to a ring nitrogen atom, R 1 , R 2 , R 3 and R 4 are independently hydrogen, C 1-6 alkyl, halo C 1-6 alkyl, heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy C 2-6 alkenyl, hydroxy C 2-6 alkynyl, C 1-6 alkoxy C 2-6 alkenyl, C 1-6 alkoxy C 2-6 alkynyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 3-7 cycloalkyl C 1-6 alkyl, optionally substituted heterocyclyl or optionally substituted heterocyclyl-C 1-6 alkyl;

R 5 is hydrogen, C 1-6 alkyl, heteroalkyl, or optionally substituted C 3-7 cycloalkyl;

R 6 is hydrogen, C 1-6 alkyl, heteroalkyl or C 3-7 cycloalkyl;

provided that compounds wherein Y is mono- or di-fluorosubstituted phenyl, mono- or di-methyl substituted phenyl, mono-chloro substituted phenyl, mono-methoxy substituted phenyl, mono-phenyl substituted phenyl, mono-chloro-mono-methyl substituted phenyl and mono-fluoro-mono-methoxy substituted phenyl are excluded;

or pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein

is diazepan-1-yl, piperazin-1-yl, piperidin-1-yl or pyrrolidin-1-yl.

3. The compound of claim 2 , wherein

is piperidin-1-yl.

4. The compound of claim 3 , wherein two of R 1 , R 2 , R 3 and R 4 are hydrogen, and the other two are,

when attached to a ring carbon atom, independently hydrogen, hydroxy, amino optionally substituted by one or two substituents independently selected from the group consisting of C 1-6 alkyl, heteroalkyl, optionally substituted C 3-7 cycloalkyl and optionally substituted heterocyclyl or optionally substituted heterocyclyl, in which one of the ring carbon atoms of the heterocyclyl may be a ring carbon atom of another ring which is a heterocyclyl, one or two ring carbon atoms of said other ring being optionally replaced by a carbonyl group, and

when they are attached to the same ring carbon atom, they can, together with the carbon atom to which they are attached, form a heterocyclyl ring, and

when attached to a ring nitrogen atom, the other two are independently hydrogen, C 1-6 alkyl, heteroalkyl, optionally substituted C 3-7 cycloalkyl or optionally substituted heterocyclyl-C 1-6 alkyl.

5. The compound of claim 1 , wherein three of R 1 , R 2 , R 3 and R 4 are hydrogen, and the other one is attached to a ring carbon atom and optionally substituted heterocyclyl, in which one of the ring carbon atoms of the heterocyclyl may be a ring carbon atom of another ring which is a heterocyclyl, one or two ring carbon atoms of said other ring being optionally replaced by a carbonyl group.

6. The compound of claim 5 , wherein three of R 1 , R 2 , R 3 and R 4 are hydrogen, and the other one is attached to a ring carbon atom and optionally substituted pyrrolidin-1-yl, in which one of the ring carbon atoms of the pyrrolidin-1-yl may be a ring carbon atom of another ring which is a heterocyclyl, one or two ring carbon atoms of said other ring being optionally replaced by a carbonyl group.

7. The compound of claim 6 , wherein R 5 is C 1-6 alkyl or optionally substituted C 3-7 cycloalkyl.

8. The compound of claim 7 , wherein R 5 is methyl or cyclopropyl.

9. The compound of claim 8 , wherein R 6 is C 1-6 alkyl.

10. The compound of claim 9 , wherein R 6 is methyl.

11. The compound of claim 10 , wherein Y is phenyl, said phenyl being substituted by one or two substituents independently selected from the group consisting of C 1-8 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyoxy, halogen, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted C 3-7 cycloalkylvinyl, optionally substituted phenylvinyl, C 1-6 alkylethynyl, optionally substituted phenylethynyl, halo C 1-6 alkyl carbonylamino and optionally substituted phenylcarbonylamino.

12. The compound of claim 11 , wherein Y is phenyl, said phenyl being substituted by one or two substituents independently selected from the group consisting of chloro, halo C 1-6 alkyl and halo C 1-6 alkyoxy.

13. The compound of claim 12 , wherein Y is phenyl, said phenyl, being substituted by one substituent which is halo C 1-6 alkyl or halo C 1-6 alkyoxy.

14. The compound of claim 13 , wherein Y is phenyl said phenyl being substituted by one substituent which is trifluoromethyl or trifluoromethoxy.

15. A compound of claim 1 selected from the group consisting of

[5-Cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone,

[5-Cyclopropyl-3-methyl-1-(3-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone,

[5-Cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazol-4-yl]-[4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone,

7-{1-[5-Cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carbonyl]-piperidin-4-yl}-1,3,7-triaza-spiro[4.4]nonane-2,4-dione,

[5-Cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazol-4-yl]-[4-((R)-3-hydroxy-pyrrolidin-1-yl)-piperidin-1-yl]-methanone,

N—((R)-1-{1-[5-Cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carbonyl]-piperidin-4-yl}-pyrrolidin-3-yl)-acetamide,

[5-Cyclopropyl-3-methyl-1-(3-trifluoromethyl-phenyl)-1H-pyrazol-4-yl]-[4-((S)-2-hydroxymethyl-pyrrolidin-1-yl)-piperidin-1-yl]-methanone,

N—((R)-1-{1-[5-Cyclopropyl-3-methyl-1-(3-trifluoromethyl-phenyl)-1H-pyrazole-4-carbonyl]-piperidin-4-yl}-pyrrolidin-3-yl)-acetamide and

N—((3R,5S)-1-{1-[5-Cyclopropyl-3-methyl-1-(3-trifluoromethoxy-phenyl)-1H-pyrazole-4-carbonyl]-piperidin-4-yl}-5-hydroxymethyl-pyrrolidin-3-yl)-acetamide.

16. A process for manufacturing compounds of formula (I)

comprising a step of reacting compounds of formula (II)

with compounds of formula (III)

, wherein

R 1 , R 2 , R 3 , R 4 , X and Y are as defined in claim 1 .

17. A Pharmaceutical composition comprising a compound of the formula

, wherein

is a non-aromatic mono-cyclic radical of four to eight ring atoms, in which one or two ring atoms are nitrogen atoms with the remaining ring atoms being carbon atoms;

provided that, when

contains the second ring nitrogen atom, said ring nitrogen atom is not directly bonded to another heteroatom or to a carbonyl group;

X

Y is phenyl, said phenyl being substituted by one, two or three substituents independently selected from the group consisting of C 1-8 alkyl, halo C 1-6 alkyl, C 1-6 alkoxy, halo C 1-6 alkyoxy, halogen, cyano, optionally substituted phenyl, optionally substituted heteroaryl, optionally substituted C 3-7 cycloalkyl, optionally substituted heterocyclyl, C 1-6 alkylvinyl, halo C 1-6 alkylvinyl, optionally substituted C 3-7 cycloalkylvinyl, optionally substituted heterocyclylvinyl, optionally substituted phenylvinyl, optionally substituted heteroarylvinyl, C 1-6 alkylethynyl, halo C 1-6 alkylethynyl, optionally substituted C 3-7 cycloalkylethynyl, optionally substituted heterocyclylethynyl, optionally substituted phenylethynyl, optionally substituted heteroarylethynyl, C 1-6 alkylcarbonylamino, halo C 1-6 alkyl carbonylamino, optionally substituted C 3-7 cycloalkylcarbonylamino, optionally substituted heterocyclylcarbonylamino, optionally substituted phenylcarbonylamino and optionally substituted heteroarylcarbonylamino;

R 1 , R 2 , R 3 and R 4 when attached to a ring carbon atom, independently are selected from the group consisting of hydrogen, C 1-6 alkyl, halo C 1-6 alkyl, heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy C 2-6 alkenyl, hydroxy C 2-6 alkynyl, C 1-6 alkoxy C 2-6 alkenyl, C 1-6 alkoxy C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, halo C 1-6 alkoxy, heteroalkoxy, halogen, optionally substituted phenyl, optionally substituted C 3-7 cycloalkyl, optionally substituted C 3-7 cycloalkyl C 1-6 alkyl, optionally substituted heteroaryl, optionally substituted phenyl-C 1-6 alkyl, optionally substituted heteroaryl-C 1-6 alkyl, optionally substituted heterocyclyl-C 1-6 alkyl, nitro, carboxy, formyl, acyl, C 1-6 alkoxycarbonyl, carbamoyl, mono- or di-C 1-6 alkyl substituted aminocarbonyl, C 1-6 alkylthio, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl or amino optionally substituted by one or two substituents independently selected from C 1-6 alkyl, acyl, heteroalkyl, optionally substituted C 3-7 cycloalkyl and optionally substituted heterocyclyl, and or optionally substituted heterocyclyl, in which one of the ring carbon atoms of the heterocyclyl may be a ring carbon atom of another ring which is C 3-7 cycloalkyl or heterocyclyl, one or two ring carbon atoms of said another ring being optionally replaced by a carbonyl group; and

when two of R 1 , R 2 , R 3 and R 4 are attached to the same ring carbon atom, they can, together with the carbon atom to which they are attached, form a C 3-7 cycloalkyl ring or heterocyclyl ring; or

when attached to a ring nitrogen atom, R 1 , R 2 , R 3 and R 4 are independently hydrogen, C 1-6 alkyl, halo C 1-6 alkyl, heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy C 2-6 alkenyl, hydroxy C 2-6 alkynyl, C 1-6 alkoxy C 2-6 alkenyl, C 1-6 alkoxy C 2-6 alkynyl, optionally substituted C 3-7 cycloalkyl, or optionally substituted C 3-7 cycloalkyl C 1-6 alkyl, optionally substituted heterocyclyl or optionally substituted heterocyclyl-C 1-6 alkyl;

R 5 is hydrogen, C 1-6 alkyl, heteroalkyl, or optionally substituted C 3-7 cycloalkyl;

R 6 is hydrogen, C 1-6 alkyl, heteroalkyl or C 3-7 cycloalkyl;

provided that the compounds wherein Y is mono- or di-fluorosubstituted phenyl, mono- or di-methyl substituted phenyl, mono-chloro substituted phenyl, mono-methoxy substituted phenyl, mono-phenyl substituted phenyl, mono-chloro-mono-methyl substituted phenyl and mono-fluoro-mono-methoxy substituted phenyl are excluded;

or a pharmaceutically acceptable salt thereof

and a pharmaceutically acceptable excipient.