Sulfonamide derivatives

1. A compound of the formula (I):

wherein

Z is selected from the group consisting of 2-thiazolyl, 4-thiazolyl, 1-thia-3,4-diazolyl, and 1-thia-2,4-diazolyl,

in which each may be optionally substituted on a ring carbon atom with one or more substituents selected from the group consisting of halo, cyano, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo(C 1 -C 4 )alkoxy, (C 3 -C 8 )cycloalkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl-S—, amino, (C 1 -C 4 )alkylamino, di(C 1 -C 4 )alkylamino, amino(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl, and di[(C 1 -C 4 )alkyl]amino(C 1 -C 4 )alkyl;

Y 1 , Y 2 , Y 3 and Y 4 are each independently CH or CR 1 ;

each R 1 is independently selected from the group consisting of halo, cyano, amino, hydroxy, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo(C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, —C(O)H, —C(O)(C 1 -C 4 )alkyl, and —C(O)N(R 2 ) 2 ;

each R 2 is independently hydrogen, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, hydroxy(C 1 -C 4 )alkyl, or (C 3 -C 6 )cycloalkyl; or, where a nitrogen is substituted with two R 2 groups, each independently selected from (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, or hydroxy(C 1 -C 4 )alkyl, they may be taken together with the N atom to which they are attached to form a 4- to 6-membered ring which, when so formed, may therefore optionally be substituted with hydrogen, alkyl, halo, hydroxy, hydroxyalkyl or haloalkyl;

B is phenyl which may be optionally substituted with one or more substituents selected from the group consisting of halo, cyano, hydroxy, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo(C 1 -C 4 )alkoxy, cyano(C 1 -C 4 )alkyl, amino, (C 1 -C 4 )alkylamino, di(C 1 -C 4 )alkylamino, amino(C 1 -C 4 )alkyl, (C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl, di[(C 1 -C 4 )alkyl]amino(C 1 -C 4 )alkyl, trifluoromethylthio, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, —C(O)R 2 , —C(O)OR 2 , —OC(O)R 2 , —C(O)—N(R 2 ) 2 , —CH 2 —C(O)R 2 , —CH 2 —C(O)OR 2 , —CH 2 —OC(O)R 2 , —CH 2 —C(O)—N(R 2 ) 2 , S(O) 2 R 2 , S(O) 2 N(R 2 ) 2 , (C 3 -C 8 )cycloalkyl, and (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl;

X is absent;

C is selected from the group consisting of pyrazolyl; pyridinyl; pyridazinyl; and, pyrimidinyl,

in which each may be optionally substituted on a ring carbon atom with one or more substituents selected from the group consisting of halo, cyano, hydroxy, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo(C 1 -C 4 )alkoxy, N(R 2 ) 2 , (R 2 ) 2 N(C 1 -C 4 )alkyl, trifluoromethylthio, hydroxy(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy(C 1 -C 4 )alkyl, —C(O)R 2 , —C(O)OR 2 , —OC(O)R 2 , —C(O)—N(R 2 ) 2 , —CH 2 —C(O)R 2 , —CH 2 —C(O)OR 2 , —CH 2 —OC(O)R 2 , —CH 2 —C(O)—N(R 2 ) 2 , S(O) 2 R 2 , S(O) 2 N(R 2 ) 2 , (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkoxy, (C 3 -C 8 )cycloalkylamino, (C 3 -C 8 )cycloalkylamino(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkylamino, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkylamino(C 1 -C 4 )alkyl, (C 3 -C 8 )cycloalkyl(C 1 -C 4 )alkoxy;

or a tautomer thereof, or a pharmaceutically acceptable salt or solvate of the compound of formula (I), or its tautomer.

2. A compound of formula (I), or a pharmaceutically acceptable salt, solvate or tautomer thereof, as claimed in claim 1 , wherein Y 1 is CR 1 , and Y 2 , Y 3 and Y 4 are each CH; or Y 1 and Y 3 are CR 1 and Y 2 and Y 4 are CH.

3. A compound of formula (I), or a pharmaceutically acceptable salt, solvate or tautomer thereof, as claimed in claim 2 , wherein each R 1 is independently selected from halo; cyano; (C 1 -C 4 )alkyl; halo(C 1 -C 4 )alkyl; (C 1 -C 4 )alkoxy; and —C(O)NH 2 .

4. A compound of formula (I), or a pharmaceutically acceptable salt, solvate or tautomer thereof, as claimed in claim 1 , wherein B is unsubstituted, or is substituted with one or two substituents independently selected from the group consisting of halo, halo(C 1 -C 4 )alkyl, and halo(C 1 -C 4 )alkoxy.

5. A compound of formula (I), or a pharmaceutically acceptable salt, solvate or tautomer thereof, as claimed in claim 1 , selected from the group consisting of:

4-[2-(6-Aminopyridin-3-yl)-4-fluorophenoxy]-N-(5-chloro-1,3-thiazol-2-yl)-3-cyanobenzenesulfonamide;

4-[4-Chloro-2-(1H-pyrazol-4-yl)phenoxy]-3-cyano-N-1,3-thiazol-2-ylbenzenesulfonamide;

3-cyano-4-[2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethoxy)phenoxy]-N-1,3-thiazol-2-ylbenzenesulfonamide;

N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-4-[4-fluoro-2-(1H-pyrazol-4-yl)phenoxy]benzenesulfonamide;

N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-4-[4-chloro-2-(1H-pyrazol-4-yl)phenoxy]benzenesulfonamide;

4-[2-(2-aminopyridin-4-yl)-4-chlorophenoxy]-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;

2,5-difluoro-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

2,5-difluoro-4-[2-(1H-pyrazol-4-yl)-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-(4-chloro-2-(1H-pyrazol-4-yl)phenoxy)-3-cyano-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide;

4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

3-cyano-4-[2-(1H-pyrazol-5-yl)-4-(trifluoromethoxy)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

3-cyano-4-[2-(1-methyl-1H-pyrazol-5-yl)-4-(trifluoromethoxy)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

3-cyano-4-[2-(5-methyl-1H-pyrazol-4-yl)-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-{2-[2-(aminomethyl)pyridin-4-yl]-4-chlorophenoxy}-5-chloro-2-fluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

3-cyano-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-[2-(5-amino-1H-pyrazol-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;

4-[4-chloro-5-fluoro-2-(1H-pyrazol-4-yl)phenoxy]-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

2,5-difluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-[2-(2-aminopyridin-4-yl)-4-chlorophenoxy]-5-chloro-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;

3-cyano-4-[2-pyridazin-4-yl-4-(trifluoromethoxy)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-{4-Chloro-2-[2-(dimethylamino)pyridin-4-yl]phenoxy}-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-{4-Chloro-2-[2-(cyclobutyloxy)pyridin-4-yl]phenoxy}-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

4-{4-Chloro-2-[2-(dimethylamino)pyridin-4-yl]phenoxy}-3-cyano-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

5-chloro-2-fluoro-4-[2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;

4-[2-(3-amino-1H-pyrazol-4-yl)-4-(trifluoromethyl)phenoxy]-5-chloro-2-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;

4-[2-(3-amino-1H-pyrazol-4-yl)-4-(trifluoromethyl)phenoxy]-5-chloro-2-fluoro-N-1,3-thiazol-4-ylbenzenesulfonamide;

5-Chloro-2-fluoro-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide;

3-Cyano-4-[5-fluoro-2-pyridazin-4-yl-4-(trifluoromethyl)phenoxy]-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide;

2-fluoro-5-methyl-4-[2-pyridazin-4-yl-4-(trifluoromethoxy)phenoxy]-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide.

6. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt, solvate or tautomer thereof, as claimed in claim 1 , and one or more pharmaceutically acceptable excipients.

7. A pharmaceutical composition as claimed in claim 6 comprising one or more additional therapeutic agents.

8. A method of treating pain in a mammal comprising administering to a mammal requiring such treatment an effective amount of a compound of the formula (I), or a pharmaceutically acceptable salt, solvate or tautomer thereof, according to claim 1 .