Bis-(Sulfonylamino) Derivatives in Therapy 205

Abstract

The invention provides compounds of formula (I) wherein R 1 , R 3 , L 1 , L 2 , G 1 , G 2 , A and m are as defined in the specification and optical isomers, racemates and tautomers thereof, and pharmaceutically acceptable salts thereof; together with processes for their preparation, pharmaceutical compositions containing them and their use in therapy. The compounds are inhibitors of microsomal prostaglandin E synthase-1.

1 . A compound of formula (I) or a pharmaceutically acceptable salt thereof 
     
       
         
         
             
             
         
       
     
     wherein:
 A is selected from phenyl or a 5- or 6-membered heteroaryl or a 5- or 6-membered heterocyclenyl moiety; said phenyl or 5- or 6-membered heteroaryl or 5- or 6-membered heterocyclenyl moiety in group A being optionally fused to a phenyl, a 5- or 6-membered heteroaryl, C 5-6 carbocyclyl or C 5-6 heterocyclyl ring; 
 each R 1  is independently selected from halogen, nitro, SF 5 , CN, NR 5 R 6 , OH, CHO, CO 2 C 1-4 alkyl, CONR 5 R 6 , C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, G 3 , OG 3  or OCH 2 G 3 ; said C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl or C 1-4 alkoxy being optionally substituted by one or more substituents selected from OH, NR 5 R 6 , C 1-4 alkyl or F; 
 m represents an integer 0, 1, 2, 3 or 4; 
 each R 3 is independently selected from hydrogen, CN and C 1-4 alkyl; said C 1-4 alkyl being optionally substituted with OH, CN, C 1-4 alkoxy, NR 7 R 8 , or one or more F atoms; 
 L 1  represents a direct bond, C 1-4 alkylene, C 2-4 alkenylene or C 2-4 alkynylene; 
 L 2  represents a direct bond, —O—, —OCH 2 —, C 1-2 alkylene, —C≡C— or —NHCONH—; 
 G 1  represents phenyl, 5- or 6-membered heteroaryl, C 3-10 carbocyclyl or C 5-8 heterocyclyl; 
 G 2  represents H, C 1-6 alkyl, phenyl, 5- or 6-membered heteroaryl, C 3-10 carbocyclyl or C 5-8 heterocyclyl; said C 1-6 alkyl being optionally further substituted by one or more groups selected from OH, C 1-6 alkoxy and halogen; 
 the phenyl, heteroaryl, carbocyclyl or heterocyclyl moieties in G 1  and G 2  being optionally fused to one or two further rings independently selected from phenyl, a 5- or 6-membered heteroaryl, C 5-6 carbocyclyl or C 5-6  heterocyclyl ring; 
 any phenyl, heteroaryl, carbocyclyl or heterocyclyl moieties in G 1  and G 2  being optionally substituted by one or more substituents independently selected from halogen, OH, CN, NO 2 , CO 2 R 9 , C 1-6 alkyl, C 1-6 alkoxy, C 1-4 thioalkoxy, SO 2 NR 10 R 11 , NR 12 R 13 , —NHCOC(OH)(CH 3 )CF 3  or —CH 2 OCH 2 CF 2 CHF 2 ; said C 1-6 alkyl or C 1-6 alkoxy being optionally substituted by OH or by one or more F atoms; 
 R 9  represents C 1-6 alkyl; 
 G 3  represents phenyl or 5- or 6-membered heteroaryl; and 
 each, R 4 , R 5 , R 6 , R 7 , R 8 , R 10 , R 11 , R 12  and R 13  is independently selected from H or C 1-4 alkyl; 
 with the proviso that the following compounds are excluded: 
 3-[(phenylsulfonyl)amino]pyridine-2-sulfonamide; 
 2-amino-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 4-tert-butyl-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 3-amino-4-hydroxy-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 4-bromo-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 4-fluoro-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 4-methyl-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 4-nitro-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 2-nitro-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 4-amino-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 2-[(phenylsulfonyl)amino]-4-(trifluoromethyl)benzenesulfonamide; 
 2-{[(4-methylphenyl)sulfonyl]amino }-4-(trifluoromethyl)benzenesulfonamide; N-(2-sulfamoylphenyl)quinoline-8-sulfonamide; 
 4-tert-butyl-N-(2-(N-ethylsulfamoyl)phenyl)-2,6-dimethylbenzenesulfonamide; 
 2,5-dibromo-N-(2-(N-ethylsulfamoyl)phenyl)benzenesulfonamide; 
 methyl 4-(5-fluoro-3-methylbenzo[b]thiophene-2-sulfonamido)-3-sulfamoylbenzoate; 
 2,3,4,5,6-pentafluoro-N-(2-sulfamoylphenyl)benzenesulfonamide; 
 N-(2-(N,N-dimethylsulfamoyl)phenyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 N-(2-(N-tert-butylsulfamoyl)phenyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 N-(2-(N-methoxy-N-methylsulfamoyl)phenyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 5,7-dimethyl-N-(2-sulfamoylphenyl)-[1,2,4]triazolo[1,5-c]pyrimidine-2-sulfonamide; 
 6-methyl-N-(2-sulfamoylphenyl)thiazolo[3,2-b][1,2,4]triazole-2-sulfonamide; 
 6-chloro-N-(2-(N,N-dimethylsulfamoyl)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 6-chloro-N-(2-(N-ethyl-N-methylsulfamoyl)phenyl)-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 N-(2-(N,N-dimethylsulfamoyl)phenyl)-5-methyl-7,8-dihydro-6H-cyclopenta[e][1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 N-(2-(N,N-dimethylsulfamoyl)-5-(trifluoromethyl)phenyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; 
 N-(2-(N-ethyl-N-methylsulfamoyl)phenyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide; and 
 N-(2-(N,N-dimethylsulfamoyl)phenyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide. 
 
   
   
       2 . A compound according to  claim 1  wherein each R 3  represents hydrogen. 
   
   
       3 . A compound according to  claim 1  wherein A represents phenyl, pyridyl, thienyl or 2,3-dihydro-indenyl. 
   
   
       4 . A compound according to  claim 1  wherein m represents an integer 0, 1 or 2. 
   
   
       5 . A compound according to  claim 1  wherein L 1  represents a direct bond, C 1-3 alkylene or C 2-3 alkenylene. 
   
   
       6 . A compound according to  claim 1  wherein L 2  represents a direct bond, —O—, —OCH 2 —, —NHCONH— or —C≡C—. 
   
   
       7 . A compound according to  claim 1  wherein G 1  represents phenyl or 5- or 6-membered heteroaryl, said phenyl or 5- or 6-membered heteroaryl being optionally fused to one or two further rings independently selected from phenyl, C 5-6 carbocyclyl or C 5-6  heterocyclyl ring. 
   
   
       8 . A compound according to  claim 7  wherein G 1  represents phenyl, naphtyl, pyridyl, thienyl, 2,3-dihydro-indenyl tetrahydronaphtyl, 2,3-dihydro-1,4-benzodioxinyl or S,S, -dioxodibenzothienyl. 
   
   
       9 . A compound according to  claim 1  wherein G 2  represents H, C 1-6 alkyl, phenyl, 5- or 6-membered heteroaryl, C 3-10 carbocyclyl or C 5-8 heterocyclyl;
 said phenyl or 5- or 6-membered heteroaryl being optionally fused to one further ring independently selected from phenyl, a 5- or 6-membered heteroaryl, C 5-6 carbocyclyl and C 5-6  heterocyclyl ring;   said C 1-6 alkyl being optionally further substituted by one or more groups selected from OH, C 1-6 alkoxy and halogen.   
   
   
       10 . A compound according to  claim 9  wherein G 2  represents hydrogen, methyl, ethyl, tert-butyl, iso-propyl, phenyl, pyridyl, pyrimidyl, cyclopentyl, cyclopentenyl, cyclohexyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, pyrazolyl, bensofuranyl, 2,3-dihydro-bensofuranyl, indolyl, tetrahydronaphtyl or dibenzofuranyl. 
   
   
       11 . A compound according to  claim 1  wherein R 5  and R 6  is hydrogen. 
   
   
       12 . A compound according to  claim 1  wherein R 10  is hydrogen. 
   
   
       13 . A compound according to  claim 1  wherein R 11 , R 12  and R 13  is methyl. 
   
   
       14 . A compound according to  claim 1  wherein R 1  is independently selected from halogen, CN, OH, CONR 5 R 6 , NR 5 R 6 , C 1-4 alkyl, C 2-4 alkynyl, C 1-4 alkoxy, G 3 , OG 3  and OCH 2 G ; said C 1-4 alkyl or C 2-4 alkynyl being optionally substituted by OH. 
   
   
       15 . A compound according to  claim 1  wherein G 3  is phenyl, pyridyl or 2-methyl-1,3,4-oxadiazole. 
   
   
       16 . A compound according to  claim 1  wherein any phenyl, heteroaryl, carbocyclyl or heterocyclyl moieties in G 1  and G 2  are optionally substituted by one or more substituents independently selected from halogen, CN, OH, C 1-4 alkyl, C 1 thioalkoxy, NR 12 R 13 , —NHCOC(OH)(CH 3 )CF 3 , SO 2 NR 10 R 11l , and C   1 alkoxy; said C 1-4 alkyl or C 1 alkoxy being optionally substituted by OH or by one or more F atoms. 
   
   
       17 . A compound according to  claim 1  wherein A is phenyl, pyridyl, thienyl or 2,3-dihydro-indenyl;
 R 1  is independently selected from halogen, CN, OH, CONR 5 R 6 , NR 5 R 6 , C 1-4 alkyl, C 2-4 alkynyl, C 1-4 alkoxy, G 3 , OG 3  and OCH 2 G 3 ; said C 1-4 alkyl or C 2-4 alkynyl being optionally substituted by one or more substituents selected from OH and C 1-4 alkyl;   m represents an integer 0, 1 or 2;   G 3  is phenyl, pyridyl or 2-methyl-1,3,4-oxadiazole;   R 3 , R 5 , R 6  and R 10  represents hydrogen;   L 1  represents a direct bond, C 1-3 alkylene or C 2-3 alkenylene;   L 3  represents a direct bond, —O—, —OCH 2 —, —NHCONH— or —C≡C—;   G 1  represents phenyl or 5- or 6-membered heteroaryl; said phenyl or 5- or 6-membered heteroaryl being optionally fused to one or two further rings independently selected from phenyl, C 5-6 carbocyclyl or C 5-6  heterocyclyl ring;   G 2  represents H, C 1-6 alkyl, phenyl, 5- or 6-membered heteroaryl, C 3-10 carbocyclyl or C 5-8 heterocyclyl; said phenyl or 5- or 6-membered heteroaryl being optionally fused to one further ring independently selected from phenyl, a 5- or 6-membered heteroaryl, C 5-6 carbocyclyl or C 5-6  heterocyclyl ring; said C 1-6 alkyl being optionally further substituted by one or more groups selected from OH, C 1-6 alkoxy and halogen;   any phenyl, heteroaryl, carbocyclyl or heterocyclyl moieties in G 1  and G 2  being optionally substituted by one or more substituents independently selected from halogen, CN, OH, C 1-4 alkyl, C 1 thioalkoxy, NR 12 R 13 , —NHCOC(OH)(CH 3 )CF 3 , SO 2 NR 10 R 11 , and C 1 alkoxy; said C 1-4 alkyl or C 1 alkoxy being optionally substituted by OH or by one or more F atoms; and   R 11 , R 12  and R 13  are methyl.   
   
   
       18 . A compound according to  claim 1  wherein A is phenyl, pyridyl, thienyl or 2,3-dihydro-indenyl;
 R 1  is independently selected from chloro, fluoro, bromo, CN, OH, CONR 5 R 6 , methyl, 1-butynyl, methoxy, G 3 , OG 3  or OCH 2 G 3 ; said methyl and 1-butynyl being optionally substituted by OH or methyl;   m represents an integer 0, 1 or 2;   G 3  is phenyl, pyridyl or 2-methyl-1,3,4-oxadiazole;   R 3 , R 5 , R 6  and R 10  represents hydrogen;   L 1  represents a direct bond, ethylene, 1-methylethylene, 2-methylethylene, ethenylene, —C(CH3)CH —, —CHC(CH3)— or —CH2C(CH2)—;   L 2  represents a direct bond, —O—, —OCH 2 —, —NHCONH— or —C≡C—;   G 1  represents phenyl, naphtyl, pyridyl, thienyl, 2,3-dihydro-indenyl tetrahydronaphtyl, 2,3-dihydro-1,4-benzodioxinyl or S,S,-dioxodibenzothienyl;   G 2  represents hydrogen, methyl, ethyl, tert-butyl, iso-propyl phenyl, pyridyl, pyrimidyl, cyclopentyl, cyclopentenyl, cyclohexyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, pyrazolyl, bensofuranyl, 2,3-dihydro-bensofuranyl, indolyl, tetrahydronaphtyl or dibenzofuranyl;   any methyl, ethyl, tert-butyl, iso-propyl phenyl, pyridyl, pyrimidyl, cyclopentyl, cyclopentenyl, cyclohexyl, furanyl, tetrahydrofuranyl, thienyl, thiazolyl, pyrazolyl, bensofuranyl, 2,3-dihydro-bensofuranyl, indolyl, tetrahydronaphtyl or dibenzofuranyl in G 1  and G 2  being optionally substituted by one or more substituents independently selected from bromo, chloro, fluoro, CN, OH, methyl, tert-butyl, methylthio, NR 12 R 13 , —NHCOC(OH)(CH 3 )CF 3 , SO 2 NR 10 R 11 , and methoxy; said methyl, tert-butyl or methoxy being optionally substituted by OH or by one or more F atoms; and   R 11 , R 12  and R 13  methyl.   
   
   
       19 . A compound selected from the group consisting of:
 2-[2-(4-Benzofuran-2-ylphenyl)ethylsulfonylamino]benzenesulfonamide;   2-[2-[4-(2,3-Dihydrobenzofuran-2-yl)phenyl]ethylsulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Benzofuran-2-ylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Benzofuran-2-ylphenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Benzofuran-2-ylphenyl)ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Benzofuran-2-ylphenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[1-(4-Chlorophenyl)propan-2-ylsulfonylamino]benzenesulfonamide;   2-(1-Phenylpropan-2-ylsulfonylamino)benzenesulfonamide;   2-[[(E)-1-(4-Chlorophenyl)prop-1-en-2-yl]sulfonylamino]benzenesulfonamide;   2-[1-(4-Chlorophenyl)propan-2-ylsulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-1-(4-chlorophenyl)prop-1-en-2-yl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-1-(4-Chlorophenyl)prop-1-en-2-yl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-1-(4-Chlorophenyl)prop-1-en-2-yl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[[(E)-1-(4-Chlorophenyl)prop-1-en-2-yl]sulfonylamino]-3-fluoro-benzenesulfonamide;   2-[[(E)-1-(4-Chlorophenyl)prop-1-en-2-yl]sulfonylamino]-5-methyl-benzenesulfonamide;   2-[2-[4-(2-Furyl)phenyl]ethylsulfonylamino]benzenesulfonamide;   2-[2-[4-(Oxolan-2-yl)phenyl]ethylsulfonylamino]benzenesulfonamide;   2-[[(E)-2-[4-(2-Furyl)phenyl]ethenyl]sulfonylamino]benzenesulfonamide;   2-[2-[4-(Difluoromethoxy)phenyl]ethylsulfonylamino]benzenesulfonamide;   2-[[(E)-2-[4-(Difluoromethoxy)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-[2-(4-Chlorophenyl)ethylsulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Chlorophenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(3,4-Dichlorophenyl)ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-2-(3,4-Dichlorophenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(3,4-Dichlorophenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[[(E)-2-(5-Bromo-2-methoxy-phenyl)ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-2-(5-Bromo-2-methoxy-phenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(5-Bromo-2-methoxy-phenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[[(E)-2-(5-Bromo-2-methoxy-phenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Cyanophenyl)ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Cyanophenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Cyanophenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Cyanophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   4-Fluoro-2-[[(E)-2-[4-(2-furyl)phenyl]ethenyl]sulfonylamino]benzenesulfonamide;   5-Fluoro-2-[[(E)-2-[4-(2-furyl)phenyl]ethenyl]sulfonylamino]benzenesulfonamide;   2-Fluoro-6-[[(E)-2-[4-(2-furyl)phenyl]ethenyl]sulfonylamino]benzenesulfonamide;   4-Fluoro-2-[[(E)-2-(4-methylsulfanylphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   5-Fluoro-2-[[(E)-2-(4-methylsulfanylphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   2-Fluoro-6-[[(E)-2-(4-methylsulfanylphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   2-[[(E)-2-(4-Methylsulfanylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-[4-(Difluoromethoxy)phenyl]ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-2-[4-(Difluoromethoxy)phenyl]ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-[4-(Difluoromethoxy)phenyl]ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[2-(4-Chlorophenyl)ethylsulfonylamino]-5-(hydroxymethyl)-benzenesulfonamide;   2-[2-(4-Chloro-phenyl)-ethanesulfonylamino]-5-methylbenzenesulfonamide;   2-[2-(4-Chlorophenyl)ethylsulfonylamino]-5-(pyridin-2-ylmethoxy)benzenesulfonamide;   2-[2-(4-Chlorophenyl)ethylsulfonylamino]-5-[(5-methyl-1,3,4-oxadiazol-2-yl)methoxy]benzenesulfonamide;   2-[2-(2-Chloro-phenyl)-ethenesulfonylamino]-benzenesulfonamide;   2-[2-(4-Chloro-2-methoxy-phenyl)-ethenesulfonylamino]-benzenesulfonamide;   2-Fluoro-6-[[(E)-2-(4-phenylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(3-Chlorophenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   5-Fluoro-2-[[(E)-2-(4-phenylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   4-Fluoro-2-[[(E)-2-(4-phenylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   5-Fluoro-2-[[(E)-2-[3-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   5-Fluoro-2-[[(E)-2-(2-methoxyphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   2-[[(E)-2-(3-Chlorophenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-Fluoro-6-[[(E)-2-(2-methoxyphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   4-Fluoro-2-[[(E)-2-(2-methoxyphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   3-Fluoro-2-[[(E)-2-(4-phenylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   3-Fluoro-2-[[(E)-2-(2-methoxyphenyl)ethenyl]sulfonylamino]-benzenesulfonamide;   4-Fluoro-2-[[(E)-2-[3-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-Fluoro-6-[[(E)-2-(2-fluorophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(3-Chlorophenyl)ethenyl]sulfonylamino]-5-methyl-benzenesulfonamide;   2-[[(E)-2-(3-Chlorophenyl)ethenyl]sulfonylamino]-3-fluoro-benzenesulfonamide;   3-Fluoro-2-[[(E)-2-[3-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-Fluoro-6-[[(E)-2-[3-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   4-Fluoro-2-[[(E)-2-(2-fluorophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   5-Methyl-2-[[(E)-2-[3-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-[2-(4-Cyclopentylphenyl)ethylsulfonylamino]benzenesulfonamide;   2-[2-(4-Tert-butylphenyl)ethylsulfonylamino]benzenesulfonamide;   4-Fluoro-2-[2-(4-tert-butylphenyl)ethylsulfonylamino]benzenesulfonamide;   2-[2-(4-Chlorophenyl)ethylsulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Chlorophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-(Phenethylsulfonylamino)benzenesulfonamide;   2-[[(E)-2-Phenylethenyl]sulfonylamino]benzenesulfonamide;   2-[2-(2-Chlorophenyl)ethylsulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Methoxyphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Chlorophenyl)ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   2-(2-Phenylpropylsulfonylamino)benzenesulfonamide;   2-[[(E)-2-(4-Chlorophenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   2-[[(E)-2-(2,6-Dichlorophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Methylphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(2-Methoxyphenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-Naphthalen-2-ylethenyl]sulfonylamino]benzenesulfonamide;   2-[2-(4-Chlorophenyl)ethylsulfonylamino]-4-fluoro-benzenesulfonamide;   2-[[(E)-2-(4-Chlorophenyl)prop-1-enyl]sulfonylamino]benzenesulfonamide;   2-[2-(4-Chlorophenyl)prop-2-enylsulfonylamino]benzenesulfonamide;   2-Fluoro-6-[[(E)-2-naphthalen-2-ylethenyl]sulfonylamino]benzenesulfonamide;   2-Fluoro-6-[[(E)-2-[2-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-Fluoro-6-[[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-[[(E)-2-(4-Bromophenyl)ethenyl]sulfonylamino]-6-fluoro-benzenesulfonamide;   4-Fluoro-2-[[(E)-2-naphthalen-2-ylethenyl]sulfonylamino]benzenesulfonamide;   4-Fluoro-2-[[(E)-2-[2-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   4-Fluoro-2-[[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-[[(E)-2-(4-Bromophenyl)ethenyl]sulfonylamino]-4-fluoro-benzenesulfonamide;   5-Methyl-2-[[(E)-2-naphthalen-2-ylethenyl]sulfonylamino]benzenesulfonamide;   5-Methyl-2-[[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-[[(E)-2-(4-Bromophenyl)ethenyl]sulfonylamino]-5-methyl-benzenesulfonamide;   5-Fluoro-2-[[(E)-2-naphthalen-2-ylethenyl]sulfonylamino]benzenesulfonamide;   5-Fluoro-2-[[(E)-2-[2-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   5-Fluoro-2-[[(E)-2-[4-(trifluoromethyl)phenyl]ethenyl]sulfonylamino]-benzenesulfonamide;   2-[[(E)-2-(4-Bromophenyl)ethenyl]sulfonylamino]-5-fluoro-benzenesulfonamide;   2-[[(E)-2-(2,6-Difluorophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-[2-(Trifluoromethyl)phenyl]ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-[4-(Trifluoromethyl)phenyl]ethenyl]sulfonylamino]benzenesulfonamide;   2-[[(E)-2-(4-Bromophenyl)ethenyl]sulfonylamino]benzenesulfonamide;   2-[(E)-2-(4-Bromophenyl) ethylsulfonylamino]benzenesulfonamide;   2-[2-(4-Chlorophenyl)propylsulfonylamino]benzenesulfonamide;   2-[2-(2-Methoxyphenyl)ethylsulfonylamino]benzenesulfonamide;   2-(2-Naphthalen-2-ylethylsulfonylamino)benzenesulfonamide;   4-Fluoro-2-(2-naphthalen-2-ylethylsulfonylamino)benzenesulfonamide;   2-[(4-Chlorophenyl)methylsulfonylamino]benzenesulfonamide;   2-[[3-(2,3-Dichlorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-(3,5-difluorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   3-(5-Chloro-2-methoxy-phenyl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(3-Cyanophenyl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-(4-Cyanophenyl)phenyl]sulfonylamino]benzenesulfonamide;   3-(2,4-Dimethoxypyrimidin-5-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(3-Furyl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-(1H-Indol-5-yl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-[3-(Trifluoromethoxy)phenyl]phenyl]sulfonylamino]benzenesulfonamide;   N-(2-Sulfamoylphenyl)-2,3-dihydro-1H-indene-5-sulfonamide;   7-Methyl-N-(2-sulfamoylphenyl)-10-oxa-7-azabicyclo[4.4.0]deca-1,3,5-triene-3-sulfonamide;   2-(3,4-Dichlorophenyl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[4-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]oxyphenyl]sulfonylamino]benzenesulfonamide;   N-(2-Sulfamoylphenyl)tetralin-2-sulfonamide;   4-Phenylmethoxy-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[(4-Cyclohexylphenyl)sulfonylamino]benzenesulfonamide;   3-Phenyl-N-(2-sulfamoylphenyl)benzenesulfonamide;   5-(1-Methyl-5-trifluoromethyl-1H-pyrazol-3-yl)-thiophene-2-sulfonic acid (2-sulfamoyl-phenyl)-amide;   N-(2-Sulfamoylphenyl)-4-(trifluoromethyl)benzenesulfonamide;   2-[[3-(2,5-Dichlorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   3-Dibenzofuran-4-yl-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-[4-(Trifluoromethyl)phenyl]phenyl]sulfonylamino]benzenesulfonamide;   3-(3-Methoxyphenyl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   3-Benzofuran-2-yl-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(2,3-Dihydrobenzofuran-5-yl)phenyl]sulfonylamino]benzenesulfonamide;   3-(6-Methoxypyridin-3-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(2,4-Dichlorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   3-(1-Methylindol-2-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-[3-(Trifluoromethyl)phenyl]phenyl]sulfonylamino]benzenesulfonamide;   4-Benzofuran-2-yl-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(2,4-Difluorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   5-Bromo-2-[[3-(3,4-dichlorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-(3,4-Dichlorophenyl)phenyl]sulfonylamino]-5-phenyl-benzenesulfonamide;   2,3-Difluoro-N-(2-sulfamoylphenyl)benzenesulfonamide;   2,3-Difluoro-N-(4-fluoro-2-sulfamoyl-phenyl)benzenesulfonamide;   3-Chloro-2-fluoro-N-(2-sulfamoylphenyl)benzenesulfonamide;   2,3-Dichloro-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(3,4-Dichlorophenyl)phenyl]sulfonylamino]-5-methyl-benzenesulfonamide;   4-[[3-(3,4-Dichlorophenyl)phenyl]sulfonylamino]-3-sulfamoyl-benzamide;   5-Methyl-2-[[3-[3-(trifluoromethoxy)phenyl]phenyl]sulfonylamino]-benzenesulfonamide;   2-(2,3-Dichloro-benzenesulfonylamino)-5-hydroxymethyl-benzenesulfonamide;   2-(2,3-Dichloro-benzenesulfonylamino)-5-methyl-benzenesulfonamide;   2-[[3-(3,4-Dichlorophenyl)phenyl]sulfonylamino]-5-phenoxy-benzenesulfonamide;   5-Phenoxy-2-[[3-[3-(trifluoromethoxy)phenyl]phenyl]sulfonylamino]-benzenesulfonamide;   2-(2,3-Dichloro-benzenesulfonylamino)-5-hydroxy-benzenesulfonamide;   (2R)—N-[2-Chloro-4-[(2-sulfamoylphenyl)sulfamoyl]phenyl]-3,3,3-trifluoro-2-hydroxy-2-methyl-propanamide;   5-Chloro-N-(2-sulfamoylphenyl)thiophene-2-sulfonamide;   4,5-Dichloro-N-(2-sulfamoylphenyl)thiophene-2-sulfonamide;   3,4-Dichloro-N-(2-sulfamoylphenyl)benzenesulfonamide;   3-(6-Methoxypyridin-2-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[4-[(2-Chloro 1,3-thiazol-5-yl)methoxy]phenyl]sulfonylamino]-benzenesulfonamide;   3-(5-Fluoro-6-methoxy-pyridin-3-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   3-(2-Methoxypyrimidin-5-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   3-(4-Methylpyridin-3-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   3-(2-Methoxypyridin-3-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-(5-Mhloropyridin-3-yl)phenyl]sulfonylamino]benzenesulfonamide;   3-(5-Chloro-6-methoxy-pyridin-3-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   3-(6-Dimethylaminopyridin-3-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-[[3-[3-(Hydroxymethyl)phenyl]phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-[4-(Hydroxymethyl)phenyl]phenyl]sulfonylamino]benzenesulfonamide;   2-[[4-(3,4-Dichlorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[3-(3,4-Dichlorophenyl)phenyl]sulfonylamino]benzenesulfonamide;   2-[[4-(4-Chlorophenoxy)phenyl]sulfonylamino]benzenesulfonamide;   3-(4-Chlorophenyl)-1-[3-methyl-4-[(2-sulfamoylphenyl)sulfamoyl]phenyl]urea;   N-Methyl-N′-(2-sulfamoylphenyl)dibenzo[b,d]thiophene-2,8-disulfonamide 5,5-dioxide;   2,3-Dichloro-N-(4,5-difluoro-2-sulfamoylphenyl)benzenesulfonamide;   (E)-2-(2-(3,4-Dichlorophenyl)vinylsulfonamido)-5-(3-hydroxy-3-methylbut-1-ynyl)benzenesulfonamide;   4-Cyano-2-(2-(3,4-dichlorophenyl)ethylsulfonamido)benzenesulfonamide;   2-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)-4-cyanobenzenesulfonamide;   2-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)-5-cyanobenzenesulfonamide;   2-(2-(4-(3,3-dimethylbut-1-ynyl)phenyl)ethylsulfonamido)benzenesulfonamide;   2-(2-(4-(3-Hydroxy-3-methylbut-1-ynyl)phenyl)ethylsulfonamido)benzenesulfonamide;   3-(3,3-Dimethylbut-1-ynyl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   2-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)benzenesulfonamide;   2-(2-(6-(3,3-Dimethylbut-1-ynyl)pyridin-3-yl)ethylsulfonamido)benzenesulfonamide;   2-(2-(6-(cyclohexylethynyl)pyridin-3-yl)ethylsulfonamido)benzenesulfonamide;   2-(2-(4-Bromophenyl)ethylsulfonamido)-5-methylbenzenesulfonamide;   (E)-2-(2-(4-Bromophenyl)vinylsulfonamido)-5-methylbenzenesulfonamide;   3-(2-Methylthiazol-4-yl)-N-(2-sulfamoylphenyl)benzenesulfonamide;   (E)-2-(2-(3-(Trifluoromethyl)phenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(2-Fluorophenyl)vinylsulfonamido)benzenesulfonamide;   5-Chloro-2-(2-(4-chloro-2-methoxyphenyl)ethylsulfonamido)benzenesulfonamide;   2,3-Dichloro-N-(4-chloro-2-sulfamoylphenyl)benzenesulfonamide;   2,3-Dichloro-N-(3,5-difluoro-2-sulfamoylphenyl)benzenesulfonamide;   2-(2-(3,4-Dichlorophenyl)ethylsulfonamido)-4,6-difluorobenzenesulfonamide;   2-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)-4,6-difluorobenzenesulfonamide;   5-Cyano-2-(2-(3,4-dichlorophenyl)ethylsulfonamido)benzenesulfonamide; (E)-2-(2-(3,4-Dichlorophenyl)vinylsulfonamido)-4-methylbenzenesulfonamide;   2-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)-4-methylbenzenesulfonamide;   5-Chloro-2-(2-(3,4-dichlorophenyl)ethylsulfonamido)benzenesulfonamide;   4-(3-(5-Chloro-6-methoxypyridin-3-yl)phenylsulfonamido)pyridine-3-sulfonamide;   4-(2-(4-(Benzofuran-2-yl)phenyl)ethylsulfonamido)pyridine-3-sulfonamide;   2-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)-5-methylbenzenesulfonamide;   4-(2-(4-Chloro-2-methoxyphenyl)ethylsulfonamido)pyridine-3-sulfonamide;   (E)-2-(2-(4-Cyclopentenylphenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(4-(3,3-Dimethylbut-1-ynyl)phenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(4-(3-Hydroxy-3-methylbut-1-ynyl)phenyl)vinylsulfonamido)- benzenesulfonamide;   2-{2-[4-(3,3-Dimethyl-but-1-ynyl)-phenyl]-ethanesulfonylamino}-5-methyl-benzenesulfonamide;   2-{2-[4-(3,3-Dimethyl-but-1-ynyl)-phenyl]-ethanesulfonylamino}-5-hydroxymethyl-benzenesulfonamide;   2-[2-(4-Cyclopentylethynyl-phenyl)-ethanesulfonylamino]-5-hydroxymethyl-benzenesulfonamide;   2-[2-(4-Chloro-2-methoxy-phenyl)-ethanesulfonylamino]-5-hydroxymethyl-benzenesulfonamide;   3-{2-[4-(3,3-Dimethyl-but-1-ynyl)-phenyl]-ethanesulfonylamino}-thiophene-2-sulfonic acid amide;   3-[3-(5-Chloro-6-methoxy-pyridin-3-yl)-benzenesulfonylamino]-thiophene-2-sulfonic acid amide;   (E)-2-(2-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(2-(difluoromethoxy)phenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(4′-(trifluoromethyl)biphenyl-4-yl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(2-isopropoxyphenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(2-(methylthio)phenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(2-(trifluoromethoxy)phenyl)vinylsulfonamido)benzenesulfonamide;   (E)-2-(2-(2-ethoxyphenyl)vinylsulfonamido)benzenesulfonamide;   2-(2-(4-(1,1,2,2-tetrafluoroethoxy)phenyl)ethylsulfonamido)benzenesulfonamide;   2-(2-(4′-(trifluoromethyl)biphenyl-4-yl)ethylsulfonamido)benzenesulfonamide;   2-[2-(2-Hydroxy-phenyl)-ethenesulfonylamino]-benzenesulfonamide;   4-Chloro-2-(2-(4-(difluoromethoxy)phenyl)ethylsulfonamido)benzenesulfonamide;   4-Chloro-2-(2-(2-methoxyphenyl)ethylsulfonamido)benzenesulfonamide;   4-Chloro-2-(2-(4-chloro-2-methoxyphenyl)ethylsulfonamido)benzenesulfonamide;   2-(2-(3,4-Dichlorophenyl)ethylsulfonamido)-3,5-difluorobenzenesulfonamide;   2,3-Dichloro-N-(4-fluoro-5-methoxy-2-sulfamoylphenyl)benzenesulfonamide;   4-Chloro-2-(2-(3,4-dichlorophenyl)ethylsulfonamido)benzenesulfonamid;   5-Chloro-2-(2-(4-chlorophenyl)ethylsulfonamido)-4-fluorobenzenesulfonamide;   5-Chloro-2-(2-(3,4-dichlorophenyl)ethylsulfonamido)-4-fluorobenzenesulfonamide;   5-(2-(4-(Furan-2-yl)phenyl)ethylsulfonamido)-2,3-dihydro-1H-indene-4-sulfonamide;   6-(2-(4-(Furan-2-yl)phenyl)ethylsulfonamido)-2,3-dihydro-1H-indene-5-sulfonamid;   5-(2-(3,4-Dichlorophenyl)ethylsulfonamido)-2,3-dihydro-1H-indene-4-sulfonamide;   (E)-5-(2-(4-Chlorophenyl)vinylsulfonamido)-2,3-dihydro-1H-indene-4-sulfonamide;   (E)-6-(2-(4-Chlorophenyl)vinylsulfonamido)-2,3-dihydro-1H-indene-5-sulfonamide;   2-[[3-(3,4-Dichlorophenyl)phenyl]sulfonylamino]-N-methyl-benzenesulfonamide; and   2-(2-(6-((4-(Trifluoromethyl)phenyl)ethynyl)pyridin-3-yl)ethylsulfonamido)-benzenesulfonamide; or a pharmaceutically acceptable salt thereof.   
   
   
       20 . A process for the preparation of a compound of formula (I) or a pharmaceutically acceptable salt thereof as defined in  claim 1  which comprises,
 (a) reacting a compound of formula (II)   
     
       
         
         
             
             
         
       
       wherein R 1 , R 3 , A and m are as defined in formula (I), 
       with a compound of formula (III) 
     
     
       
         
         
             
             
         
       
     
     wherein L 1 , L 2 , G 1  and G 2  are as defined in formula (I) and X represents a leaving group such as a halogen; or
 (b) when L 2  represents a direct bond and G 1  and G 2  are both aromatic moieties, reacting a compound of formula (IV) 
 
     
       
         
         
             
             
         
       
       wherein Hal represents a halogen atom and R 1 , R 3 , A, m and L 1  are as defined in formula (I), with a nucleophile G 2 -M wherein M represents an organo-tin or organo boronic acid group; and optionally after (a) or (b) carrying out one or more of the following:
 converting the compound obtained to a further compound of the invention 
 forming a pharmaceutically acceptable salt of the compound. 
 
     
   
   
       21 . A pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof as claimed in  claim 1  in association with a pharmaceutically acceptable adjuvant, diluent or carrier. 
   
   
       22 . A process for the preparation of a pharmaceutical composition comprising mixing the compound of  claim 1  or a pharmaceutically acceptable salt thereof with a pharmaceutically acceptable adjuvant, diluent or carrier. 
   
   
       23 . A method for treating acute or chronic pain, moniceptive pain or neuropathic pain, comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1  or a pharmaceutically acceptable salt thereof. 
   
   
       24 . A method for treating osteoarthritis, rheumatoid arthritis, benign or malignant neoplasias, apnea, sudden infant death (SID), atherosclerosis, cancer, aneurysm, hyperthermia, myositis, Alzheimer's disease or arthritis, comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1  or a pharmaceutically acceptable salt thereof. 
   
   
       25 . A method of treating, or reducing the risk of, an inflammatory disease or condition comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1  or a pharmaceutically acceptable salt thereof. 
   
   
       26 . A method of treating, or reducing the risk of, human diseases or conditions in which modulation of microsomal prostaglandin E synthase-1 activity is beneficial comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 1  or a pharmaceutically acceptable salt thereof.