Derivatives of N′-(1,5-diphenyl-1H-pyrazol-3-yl) sulfonamide with CB1 receptor affinity

1. A compound corresponding to formula (I):

wherein:

R 1 represents

a (C 1 -C 6 )alkyl;

a (C 3 -C 7 )cycloalkyl which is unsubstituted or substituted once or several times with a (C 1 -C 3 )alkyl group;

a (C 3 -C 7 )cycloalkylmethyl which is unsubstituted or substituted once or several times on the carbocycle with a (C 1 -C 3 )alkyl;

a phenyl which is unsubstituted or mono-, di- or trisubstituted with a substituent independently chosen from a halogen atom, a (C 1 -C 4 )alkyl, a (C 1 -C 3 )alkoxy, a cyano, a trifluoromethyl radical, a trifluoromethoxy radical, an S(O) n Alk group, a (C 1 -C 3 )alkylcarbonyl group, a phenyl;

a benzyl which is unsubstituted or mono- or disubstituted with a substituent independently chosen from a halogen atom, a (C 1 -C 3 )alkyl, a (C 1 -C 3 )alkoxy; a trifluoromethyl radical;

a thienyl which is unsubstituted or substituted with a halogen atom or with an isoxazolyl;

R 2 represents a hydrogen atom or a (C 1 -C 3 )alkyl;

R 3 represents a hydrogen atom or a (C 1 -C 5 )alkyl;

R 4 , R 5 , R 6 , R 7 , R 8 and R 9 each independently represent a hydrogen atom, a halogen atom, a (C 1 -C 7 )alkyl, a (C 1 -C 5 )alkoxy, a trifluoromethyl radical or an S(O) n Alk group;

n represents 0, 1 or 2; and

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

a salt, a hydrate or a solvate thereof.

2. The compound of formula (I) as claimed in claim 1 , wherein:

R 1 represents

ethyl, isopropyl or n-butyl;

cyclohexyl;

cyclohexylmethyl;

2-chlorophenyl, 3-chlorophenyl, 2-fluorophenyl, 3-chloro-4-fluorophenyl, 4-bromo-2-ethylphenyl, 3-methylphenyl, 4-tert-butylphenyl, 3,5-dimethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, 2-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 3,5-bis(trifluoromethyl)phenyl, 2-(trifluoromethoxy)phenyl, 3-(trifluoromethoxy)phenyl, 2-(methylsulfonyl)phenyl, 3-(methylsulfonyl)phenyl, 3-acetylphenyl, 3-biphenyl or 2-biphenyl;

3-chlorobenzyl, 2-fluorobenzyl, 4-fluorobenzyl, 3-(trifluoromethyl)benzyl or 4-(trifluoromethyl)benzyl;

5-bromo-2-thienyl or 5-isoxazol-3-yl-2-thienyl;

R 2 represents hydrogen or methyl;

R 3 represents methyl or ethyl;

R 4 represents hydrogen;

R 5 is at the 4-position of the phenyl and represents bromine, chlorine or fluorine, or methoxy;

R 6 represents hydrogen;

R 7 represents hydrogen;

R 8 is at the 4-position of the phenyl and represents hydrogen, chlorine or fluorine; and

R 9 is at the 2-position of the phenyl and represents chlorine or fluorine; or a salt, a hydrate or a solvate thereof.

3. The compound of formula (I) as claimed in claim 1 , chosen from:

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]butane-1-sulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-cyclohexanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-cyclohexylmethanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-chlorobenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-4-tert-butylbenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-methoxybenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-4-methoxybenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-2-(methylsulfonyl)benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-1-(3-chlorophenyl)methanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-1-[3-(trifluoromethyl)phenyl]methanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-chloro-4-fluorobenzenesulfonamide;

N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-butane-1-sulfonamide;

3-chloro-N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]benzenesulfonamide;

4-tert-butyl-N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]benzenesulfonamide;

N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-methoxybenzenesulfonamide;

N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-cyanobenzenesulfonamide;

N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide;

N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-2-(trifluoromethoxy)benzenesulfonamide;

N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-2-(methylsulfonyl)benzenesulfonamide;

3-chloro-N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-4-fluorobenzenesulfonamide;

4-bromo-N-[[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-2-ethylbenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]ethanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]propane-2-sulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]butane-1-sulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-cyclohexanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-1-cyclohexylmethanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3-chlorobenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-2-chlorobenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3-methylbenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-4-tert-butylbenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-4-methoxybenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3-methoxybenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-4-(trifluoromethyl)benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3-(trifluoromethyl)benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-2-(trifluoromethyl)benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3-(trifluoromethoxy)benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-2-(trifluoromethoxy)benzenesulfonamide;

3-acetyl-N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]benzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]biphenyl-3-sulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-1-[4-(trifluoromethyl)phenyl]methanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-1-[3-(trifluoromethyl)phenyl]methanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3,5-dimethylbenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-3,5-bis(trifluoromethyl)benzenesulfonamide;

3-chloro-N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]benzenesulfonamide;

N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-2-fluorobenzenesulfonamide;

N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-cyanobenzenesulfonamide;

N-[[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-methoxybenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-methoxybenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-cyanobenzenesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-1-(2-fluorophenyl)methanesulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-1-(4-fluorophenyl)methanesulfonamide;

5-bromo-N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]thiophene-2-sulfonamide;

N-[[5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-1H-pyrazol-3-yl]methyl]-5-isoxazol-3-ylthiophene-2-sulfonamide;

3-chloro-N-[[1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazol-3-yl]methyl]benzenesulfonamide; and

N-[[1-(2,4-dichlorophenyl)-5-(4-methoxyphenyl)-4-methyl-1H-pyrazol-3-yl]methyl]-3-methylbenzenesulfonamide; or

a salt, a hydrate or a solvate thereof.

4. A method for preparing a compound of formula (I) as claimed in claim 1 , comprising:

reacting a compound of formula:

wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined for a compound of formula (I) in claim 1 , in the presence of a base and in a solvent, with a sulfonyl halide of formula:

wherein R 1 is as defined for a compound of formula (I) in claim 1 and Hal represents a halogen atom.

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

6. The composition according to claim 5 , wherein compound of formula (I) is having:

R 1 represents

ethyl, isopropyl or n-butyl;

cyclohexyl;

cyclohexylmethyl;

2-chlorophenyl, 3-chlorophenyl, 2-fluorophenyl, 3-chloro-4-fluorophenyl, 4-bromo-2-ethylphenyl, 3-methylphenyl, 4-tert-butylphenyl, 3,5-dimethylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-cyanophenyl, 4-cyanophenyl, 2-(trifluoromethyl)phenyl, 3-(trifluoromethyl)phenyl, 4-(trifluoromethyl)phenyl, 3,5-bis(trifluoromethyl)phenyl, 2-(trifluoromethoxy)phenyl, 3-(trifluoromethoxy)phenyl, 2-(methylsulfonyl)phenyl, 3-(methylsulfonyl)phenyl, 3-acetylphenyl, 3-biphenyl or 2-biphenyl;

3-chlorobenzyl, 2-fluorobenzyl, 4-fluoro-benzyl, 3-(trifluoromethyl)benzyl or 4-(trifluoromethyl)benzyl;

5-bromo-2-thienyl or 5-isoxazol-3-yl-2-thienyl;

R 2 represents hydrogen or methyl;

R 3 represents methyl or ethyl;

R 4 represents hydrogen;

R 5 is at the 4-position of the phenyl and represents bromine, chlorine or fluorine, or methoxy;

R 6 represents hydrogen;

R 7 represents hydrogen;

R 8 is at the 4-position of the phenyl and represents hydrogen, chlorine or fluorine; and

R 9 is at the 2-position of the phenyl and represents chlorine or fluorine.