Derivatives of N-[(1,5-diphenyl-1H-pyrazol-3-yl)methyl]sulfonamide, their preparation and their application in therapeutics

1. A compound corresponding to formula (I):

in which:

R 1 represents

a (C 1 -C 12 )alkyl, unsubstituted or substituted one or more times with substituents selected independently from a fluorine atom, a hydroxyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, a phenoxy, a trifluoromethoxy radical, a difluoromethoxy radical, a difluoromethylthio radical, a trifluoromethylthio radical;

a non-aromatic (C 3 -C 12 ) carbocyclic radical, unsubstituted or substituted one or more times with substituents selected independently from a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, a fluorine atom, a hydroxyl, a trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio, difluoromethylthio radical;

a methyl a methyl substituted with a non-aromatic (C 3 -C 12 ) carbocyclic radical, unsubstituted or substituted one or more times with substituents selected independently from a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a (C 1 -C 4 )alkylthio, a fluorine atom, a hydroxyl, a trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio, difluoromethylthio radical;

a phenyl, benzyl, benzhydryl, benzhydrylmethyl radical, in which each phenyl group is unsubstituted or substituted one or more times with substituents selected independently from a halogen atom, a hydroxyl, a methylenedioxy, a cyano, a nitro, a (C 1 -C 4 )alkylcarbonyl group or an Alk, OAlk, S(O) n Alk or OS(O) n Alk group;

a phenyl radical substituted with a heterocyclic radical selected from pyrrolyl, imidazolyl, pyridyl or pyrazolyl, said heterocyclic radical being unsubstituted or substituted one or more times with one or more substituents selected independently from a halogen atom or a (C 1 -C 4 )alkyl group;

a phenyl radical substituted with a phenyl or a phenoxy in which each phenyl group is unsubstituted or substituted one or more times with substituents selected independently from a halogen atom, a hydroxyl, a methylenedioxy, a cyano, a nitro, a (C 1 -C 4 )alkylcarbonyl group or an Alk, OAlk, S(O) n Alk or OS(O) n Alk group;

a thienyl, furyl, oxazolyl, thiazolyl, imidazolyl, pyrrolyl, pyridyl radical, said radical being unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 4 )alkyl, a trifluoromethyl group;

a tetrahydronaphthalenyl or a naphthyl unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 4 )alkyl, a di(C 1 -C 4 )alkylamino or a trifluoromethyl group;

a 2,3-dihydrobenzofuranyl unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

an indol-2-yl or an N-methylindol-2-yl;

R 2 represents a hydrogen atom, a (C 1 -C 4 )alkyl or a (C 1 -C 4 )alkylsulphonyl group;

R 3 represents a cyano, a hydroxyl, a (C 1 -C 4 )alkoxy, a cyanomethyl, a hydroxymethyl, a (C 1 -C 4 )alkoxymethyl, a fluoromethyl, a tetrazolylmethyl, an N-(methyl)tetrazolylmethyl, a tetrazolyl, an N-(methyl)tetrazolyl, a CONR 6 R 7 group, a CH 2 S(O) n (C 1 -C 4 )alkyl group, a COOR 8 group or a CH 2 NR 6 R 7 group;

R 4 and R 5 each represent independently a phenyl unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 7 )alkyl group unsubstituted or substituted one or more times with a fluorine atom, an OAlk, S(O) n Alk or OS(O) n Alk group;

R 6 and R 7 each represent independently a hydrogen atom or a (C 1 -C 4 )alkyl or R 6 and R 7 together with the nitrogen atom to which they are bound constitute a heterocyclic radical selected from pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl;

R 8 represents a (C 1 -C 4 )alkyl;

n represents 0, 1 or 2; and

Alk represents a (C 1 -C 4 )alkyl unsubstituted or substituted one or more times with a fluorine atom;

or a salt thereof or a hydrate or a solvate of said compound or said salt.

2. The compound of formula (I) according to claim 1 in which:

R 1 represents

a (C 1 -C 7 )alkyl;

a (C 3 -C 7 )cycloalkyl unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

a (C 3 -C 7 )cycloalkylmethyl unsubstituted or substituted one or more times on the carbocycle with a (C 1 -C 4 )alkyl;

a phenyl unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a cyano, a trifluoromethyl group, a trifluoromethoxy group, an S(O) n Alk group, a (C 1 -C 4 )alkylcarbonyl group, a phenyl;

a benzyl unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy; a trifluoromethyl group;

a thienyl, furyl, oxazolyl, thiazolyl, imidazolyl radical, said radical being unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 4 )alkyl, a trifluoromethyl group;

a naphthyl unsubstituted or substituted with one or more substituents selected independently from a (C 1 -C 4 )alkyl, a di(C 1 -C 4 )alkylamino;

a 2,3-dihydrobenzofuranyl unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl group;

R 2 represents a hydrogen atom or a (C 1 -C 4 )alkyl;

R 3 represents a cyano, a hydroxyl, a (C 1 -C 4 )alkoxy, a cyanomethyl, a hydroxymethyl, a (C 1 -C 4 )alkoxymethyl, a fluoromethyl, a tetrazolylmethyl, an N-(methyl)tetrazolylmethyl, a tetrazolyl, an N-(methyl)tetrazolyl, a CONR 6 R 7 group, a CH 2 S(O) n Alk group, a COOR 8 group;

R 4 and R 5 each represent independently a phenyl unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 7 )alkyl, a (C 1 -C 4 )alkoxy, a trifluoromethyl group or an S(O) n Alk group;

R 6 and R 7 each represent independently a hydrogen atom or a (C 1 -C 4 )alkyl or R 6 and R 7 together with the nitrogen atom to which they are bound constitute a heterocyclic radical selected from pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl unsubstituted or substituted one or more times with a (C 1 -C 4 )alkyl;

R 8 represents a (C 1 -C 4 )alkyl;

n represents 0, 1 or 2; and

Alk represents a (C 1 -C 4 )alkyl;

or a salt thereof or a hydrate or a solvate of said compound or said salt.

3. The compound according to claim 1 of formula I in which R 3 is a cyano.

4. The compound according to claim 1 of formula I in which R 3 is a hydroxyl.

5. The compound according to claim 1 of formula I in which R 3 is a (C 1 -C 4 )alkoxy.

6. The compound according to claim 1 of formula I in which R 3 is a (C 1 -C 4 )alkoxymethyl.

7. The compound according to claim 1 of formula I in which R 3 is a CONR 6 R 7 group.

8. The compound according to claim 1 of formula I in which R 3 is a COOR 8 .

9. The compound according to claim 1 of formula I in which R 3 is a tetrazol-1-ylmethyl or a tetrazol-2-ylmethyl.

10. The compound according to claim 1 of formula I in which:

R 1 represents:

a phenyl, benzyl, benzhydryl, benzhydrylmethyl radical, in which each phenyl group is unsubstituted or substituted one or more times with substituents selected independently from a halogen atom, a hydroxyl, a (C 1 -C 4 )alkyl, a (C 1 -C 4 )alkoxy, a methylenedioxy, a cyano, a nitro, a trifluoromethyl, a difluoromethyl, a difluoromethoxy, a trifluoromethoxy, a trifluoromethylthio, a difluoromethylthio, an S(O) n Alk group, an OS(O) n Alk group, a (C 1 -C 4 )alkylcarbonyl group;

a furyl radical unsubstituted or substituted with one or more substituents selected independently from a halogen atom, a (C 1 -C 4 )alkyl, a trifluoromethyl group;

R 2 represents a hydrogen atom or a (C 1 -C 4 )alkylsulphonyl group;

R 3 represents a cyano, a hydroxyl, a (C 1 -C 4 )alkoxy, a hydroxymethyl, a (C 1 -C 4 )alkoxymethyl, a CONR 6 R 7 group, a COORS group, a tetrazol-1-yl methyl or a tetrazol-2-ylmethyl, the groups R 6 , R 7 , R 8 being as defined for (I);

R 4 represents a 4-chlorophenyl, a 4-methoxyphenyl or a 4-OSO 2 -Alk, Alk representing a (C 1 -C 4 )alkyl unsubstituted or substituted one or more times with a fluorine atom; and

R 5 represents a 2-chlorophenyl, a 2-bromophenyl or a 2,4-dichlorophenyl;

or a salt thereof or a hydrate or a solvate of said compound or said salt.

11. The compound according to claim 1 of formula I in which:

R 1 represents a 3-chlorophenyl, 3-fluorophenyl, 3,6-difluorophenyl, 2,6-difluorophenyl, 3-methoxyphenyl, 3-trifluoromethylphenyl, 3-trifluoromethoxyphenyl, a benzyl, a 4-trifluoromethylbenzyl or a 2-trifluoromethyl-4-methylfuryl group;

R 2 represents a hydrogen atom;

R 3 represents a cyano, methoxy or dimethylaminocarbonyl group;

R 4 represents a 4-chlorophenyl, a 4-methoxy or a 4-propanesulphonyloxy; and

R 5 represents a 2,4-dichlorophenyl or a 2-chlorophenyl;

or a salt thereof or a hydrate or a solvate of said compound or said salt.

12. The compound according to claim 1 , selected from:

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-3-cyanobenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-3-trifluorobenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-2-trifluoromethoxybenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-3-methoxybenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-3-chlorobenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2-chlorophenyl)-1H-pyrazol-3-yl]methyl}-3-fluorobenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2-chlorophenyl)-1H-pyrazol-3-yl]methyl}-2-fluorobenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2-chlorophenyl)-1H-pyrazol-3-yl]methyl}-2-trifluoromethoxybenzenesulfonamide,

—N-{[5-(4-methoxyphenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-3,5-difluorobenzenesulfonamide,

—N-{[5-(4-chlorophenyl)-4-methoxy-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-3-chlorobenzenesulfonamide,

-5-(4-chlorophenyl)-3-({[(3-chlorophenyl)sulfonyl]amino}methyl)-1-(2,4-dichlorophenyl)-N-methyl-1H-pyrazole-4-carboxamide,

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-1-phenylmethanesulfonamide, and

—N-{[5-(4-chlorophenyl)-4-cyano-1-(2,4-dichlorophenyl)-1H-pyrazol-3-yl]methyl}-5-methyl-2-(trifluoromethyl)furan-3-sulfonamide;

or a salt thereof or a hydrate or a solvate of said compound or said salt.

13. A method of preparation of a compound of formula (I) according to claim 1 , comprising

reacting a compound of formula (II):

in which R 2 , R 4 , R 5 are as defined for a compound of formula (I) and R′ 3 represents R 3 or a precursor of R 3 , in the presence of a base, in a solvent, with a sulfonyl halide of formula HalSO 2 R 1 , in which R 1 is as defined for a compound of formula (I) in claim 1 and Hal represents a halogen atom; and if applicable, the compound obtained of formula:

in which R′ 3 is R 3 or is a precursor of R 3 , is converted to a compound of formula (I).

14. A pharmaceutical composition comprising a compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, or a hydrate or a solvate of said compound or said salt, in combination with at least one pharmaceutically acceptable excipient.

15. A pharmaceutical composition comprising a compound of formula (I) according to claim 12 , or a pharmaceutically acceptable salt thereof, or a hydrate or a solvate of said compound or said salt, in combination with at least one pharmaceutically acceptable excipient.