N-pyrazinyl-phenylsulphonamides and their use in the treatment of chemokine mediated diseases

Abstract

The invention provides N-pyrazinyl-phenyl-sulphonamides of formula (I) for use in the treatment of chemokine mediated diseases. Particularly inflammatory diseases, such as asthma.

1 . A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof: 
     
       
         
         
             
             
         
       
     
     in which:
 R 1 , R 2  and R 3  are independently hydrogen, halogen, cyano, CF 3 , OCF 3 , OC 1-6  alkyl or C 1-6  alkyl; 
 R 4  is halogen, CO 2 R 12 ,
 C 1-6  alkoxy where the alkyl group may form a 3-6 membered saturated ring or may be substituted with 1-3 fluorine atoms or a cyano group; 
 C 3-6  alkenyloxy or C 3-6  alkynyloxy where either may be optionally substituted with hydroxy or NR 14 R 15 ; 
 OC 1-6  alkyl-X—C 1-6  alkyl where the alkyl groups may form a 3-6 membered saturated ring; 
 OC 1-6  alkylR 11 , or OC 2-6  alkyl-X—R 11  where the alkyl group may form a 3-6 membered saturated ring and is optionally substituted with 1-3 groups selected from hydroxy, halogen, NR 14 R 15 , SR 13 , S(O) 2 R 13 , S(O)R 13  or COR 13 ; 
 OC 1-6  alkylR 16 ; 
 
 R 5  and R 6  are independently hydrogen, cyano, halogen, CO 2 R 12 , CONR 14 R 15 ;
 C 1-6  alkyl optionally substituted by hydroxy, NR 14 R 15 , or 1-3 fluorines; 
 C 1-6  alkylR 11  or XCH(R 11 )C 1-6  alkyl or XCH(R 16 )C 1-6  alkyl where the alkyl group may be optionally substituted with 1-3 groups selected from hydroxy, and NR 14 R 15 ; 
 NR 14 R 15 ; N(R 11 )R 11 ; X—(CH 2 )qNR 14 R 15 ; (CH 2 )nNR 14 R 15 ; NHC(O)C 1-6  alkyl optionally substituted by one or more hydroxy groups, 
 C 3-6  alkynyl or C 3-6  alkenyl optionally branched and optionally substituted with 1-3 groups selected from hydroxy, cyano, halogen and ═O; 
 R 11 ; X—R 11 ; X—R 12 ; X—C 1-6  alkylR 16 ; X—R 16 ; X—(CH 2 )nCO 2 R 12 ; X—(CH 2 )nCONR 14 R 15 ; 
 X—(CH 2 )nR 11 ; X—(CH 2 )nCN; X—(CH 2 )qOR 12 ; (CH 2 )nOR 12 ; 
 (CH 2 )n-X—R 11 ; X—(CH 2 )qNHC(O)NHR 12 ; X—(CH 2 )qNHC(O)R 12 ; 
 X—(CH 2 )qNHS(O) 2 R 12 ; X—(CH 2 )qNHS(O) 2 R 11 ; X—C 3-6  alkenyl; X—C 3-6  alkynyl; 
 
 n is 1, 2, 3, 4 or 5; 
 q is 2, 3, 4, 5 or 6; 
 X is NR 13 , O, S, S(O), S(O) 2 ; 
 R 11  is an aryl group or a 5-7 membered heteraromatic ring containing 1-4 heteroatoms selected from nitrogen, oxygen or sulphur each of which can be optionally substituted by 1-3 groups selected from halogen, C(O)NR 14 R 15 , C(O)OR 12 , hydroxy, ═O, ═S, CN, NO 2 , COR 13 , NR 14 R 15 , X(CH 2 )qNR 14 R 15 , (CH 2 )nNR 14 R 15 , (CH 2 )nOH, SR 13 , S(O)R 13 , S(O) 2 R 13 , C 1-6  alkyl-X—C 1-6  alkyl, C 1-6  alkyl or C 1-6  alkoxy where the alkyl group may form a 3-6 membered ring or is optionally substituted with 1-3 groups selected from hydroxy, halogen, NR 14 R 15 , SR 13 , S(O)R 13 , S(O) 2 R 13 ; 
 R 12  and R 13  are independently hydrogen or C 1-6  alkyl where the alkyl group may be substituted with 1-3 fluorine atoms or may form a saturated 3-6 membered ring; 
 R 14  and R 15  are independently hydrogen, C 1-6  alkyl, C 3-6  cycloalkyl or (CH 2 )qOH, 
 or R 14  and R 15  together with the nitrogen atom to which they are attached form a 4-8 membered saturated ring containing 1-3 heteroatoms selected from nitrogen, oxygen and sulphur and optionally substituted by C 1-6  alkyl, C 1-6  alkyl-OH, or hydroxy; and 
 R 16  is a 4-8 membered saturated ring containing 1-3 heteroatoms selected from nitrogen, oxygen or sulphur and optionally substituted with 1-3 groups selected from hydroxy, cyano, halogen and ═O, 
 provided that:
 when R 4  is halogen or C 1-4 alkoxy and R 5  is hydrogen, halogen, C 1-4 alkyl, C 1-2 alkoxy, C 1-2 alkylthio, trifluoromethyl or ethynyl and when one R 1 , R 2 , or R 3  is C 1-6 alkyl or C 1-6 alkoxy and is meta to the sulphonamide group then the group ortho to both the sulphonamide group and the C 1-6 alkyl or C 1-6 alkoxy group is not hydrogen, 
 when R 4  is halogen or C 1-4 alkoxy and R 5  is hydrogen, halogen, C 1-4 alkyl, C 1-2 alkoxy, C 1-2 alkylthio, trifluoromethyl, or ethynyl and when one of R 1 , R 2  or R 3  is C 1-6 alkyl or C 1-6 alkoxy and is ortho to the sulphonamide group then the group ortho to the C 1-6 Alkyl or C 1-6 alkoxy and also meta to the sulphonamide group is not hydrogen, 
 when two of R 1 , R 2 , R 3  are hydrogen and the other is a methyl group para to the sulphonamide and R 4  is methoxy then R 5  is not hydrogen or bromo, and 
 when R 5  is methyl and R 6  is methoxy and one of R 1 , R 2  or R 3  is bromo or iodo and the other two are both hydrogen, then the bromo or iodo group is not ortho to the sulphonamide group. 
 
 
   
   
       2 . The compound according to  claim 1  in which one of R 1 , R 2  and R 3  is hydrogen and the other is chloro, bromo or methyl. 
   
   
       3 . The compound according to  claim 1  or in which R 4  is C 1-6  alkoxy such as methoxy, 2-furanylmethoxy, bromo, chloro, 2-methoxyethoxy, (5-methyl-3-isoxazolyl)methoxy, pyridylmethoxy, 3-pyridazinylmethoxy, methoxy, 2-(1-imidazolyl)ethoxy, (2-methyl-4-oxazolyl)methoxy and 4-methoxyphenylmethoxy. 
   
   
       4 . The compound according  claim 1  in which R 5  is hydrogen, halogen such as bromo and chloro, phenyl, —C 1-6  alkyl such as methyl, CH 2 OH, cyano and
 2-aminothanethiol   
   
   
       5 . The compound according to  claim 1  in which R 6  is hydrogen,
 C 1-6  alkyl, CH 2 OH and halogen.   
   
   
       6 . The compound according to  claim 1  which is:
 2,3-Dichloro-N-(3-methoxy-5-methyl-2-pyrazinyl)-benzenesulphonamide   N-(6-Chloro-3-methoxy-2-pyrazinyl)-2,3,4-trifluorobenzenesulphonamide   3-Chloro-N-(6-chloro-3-methoxy-2-pyrazinyl)-2-methylbenzenesulphonamide   2,3-Dichloro-N-(6-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-(5-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-2,5-dichlorobenzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-3,5-dichlorobenzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-2,4-dichlorobenzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-3,4-dichlorobenzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-4-chlorobenzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-3-chlorobenzenesulphonamide   N-(3-Methoxy-5-methyl-2-pyrazinyl)-2-fluorobenzenesulphonamide   N-(3-Methoxy-5-methyl-2-pyrazinyl)benzenesulphonamide   N-(3-Methoxy-5-methyl-2-pyrazinyl)-2-iodobenzenesulphonamide   N-(3-Methoxy-5-methyl-2-pyrazinyl)-3-fluorobenzenesulphonamide   2-[[(3-Methoxy-5-methyl-2-pyrazinyl)amino]sulphonyl]benzonitrile   N-(5-Bromo-3-methoxy-2-pyrazinyl)benzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-2-iodobenzenesulphonamide   2,3-Dichloro-N-[3-(2-furanylmethoxy)-5-methyl-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(5-methyl-3-isoxazolylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(6-methyl-2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(4-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(3-methyl-2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(3-pyridazinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-(2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-(3-methoxy-2-pyrazinyl)benzenesulphonamide   N-[5-Bromo-3-(2-pyrazinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(1-methyl-6-oxo-1,6-dihydro-3-pyridinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(3-pyridazinyllmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(3-pyridinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(5-pyrimidinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Chloro-3-(3-pyridinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Chloro-3-(5-pyrimidinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   2-Chloro-N-(6-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   4-Chloro-N-(6-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   N-(6-Chloro-3-methoxy-2-pyrazinyl)-2,4-dichlorobenzenesulphonamide   N-(6-Chloro-3-methoxy-2-pyrazinyl)-3,4-dichlorobenzenesulphonamide   3-Chloro-N-(3-methoxy-5-methyl-2-pyrazinyl)-2-methylbenzenesulphonamide   2-Chloro-N-(3-methoxy-5-methyl-2-pyrazinyl)benzenesulphonamide   3-Chloro-N-(3-methoxy-5-methyl-2-pyrazinyl)benzenesulphonamide   4-Chloro-N-(3-methoxy-5-methyl-2-pyrazinyl)benzenesulphonamide   2,4-Dichloro-N-(3-methoxy-5-methyl-2-pyrazinyl)benzenesulphonamide   3,4-Dichloro-N-(3-methoxy-5-methyl-2-pyrazinyl)benzenesulphonamide   N-(5-Bromo-3-methoxy-2-pyrazinyl)-2-trifluoromethoxybenzenesulphonamide   3-Chloro-N-(5-chloro-3-methoxy-2-pyrazinyl)-2-methylbenzenesulphonamide   2-Chloro-N-(5-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   3-Chloro-N-(5-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   4-Chloro-N-(5-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   N-(5-Chloro-3-methoxy-2-pyrazinyl)-2,4-dichlorobenzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-(4-morpholinyl)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3,5-dimethoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-(1-pyrrolinyl)-2-pyrazinyl]benzenesulphonamide   3-Chloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)-2-methylbenzenesulphonamide   2,3-Dichloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   2-Chloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   3-Chloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   4-Chloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   2,4-Dichloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   3,4-Dichloro-N-(5,6-dichloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-(3-methoxy-5,6-dimethyl-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-(6-chloro-3,5-dimethoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-methoxy-5-(4-morpholinyl)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-5-(2-hydroxyethylamino)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-5-dimethylamino-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-methoxy-5-(2-methoxyethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-5-hydroxy-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-methoxy-5-([2,2′]bipyrazinyl)]benzenesulphonamide   4-[5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinyloxy]benzoic acid   2,3-Dichloro-N-(3,5-dichloro-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-{6-chloro-3-methoxy-5-([2-methoxyethyl)amino]-2-pyrazinyl}benzenesulphonamide   N-{2-[3-Chloro-5-(2,3-dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinylamino]ethyl}acetamide   2,3-Dichloro-N-[5-(4-hydroxymethyl-1-piperidinyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-cyano-3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-(6-chloro-3-methoxy-5-methylamino-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-(3-methoxy-5-methylsulphanyl-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-[5-(2,4-difluorophenyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   [5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinylsulphanyl]acetic acid methyl ester   [5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinylsulphanyl]acetic acid   2,3-Dichloro-N-[5-(2-chlorobenzylsulphanyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-5-(3-hydroxy-1-azetidinyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-methyl-3-(1-oxy-3-pyrazinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(4-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(1-oxy-4-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(2-methylsulphanylethoxy)-2-pyrazinyl]benzenesulphonamide   N-(3-Butoxy-5-chloro-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(2-methyl-3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(6-methyl-2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(1-oxy-2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   3-Chloro-N-[5-chloro-3-(3-pyridinylmethoxy)-2-pyrazinyl]-2-methylbenzenesulphonamide   3-Chloro-N-[5-chloro-3-(3-pyridinylmethoxy)-2-pyrazinyl]-2-fluorobenzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(4-methoxyphenylmethoxy)-2-pyrazinyl]benzenesulphonamide   N-[5-Bromo-6-chloro-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-(2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   N-[5-(2-Aminoethylsulphanyl)-3-(2-pyridinylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(6-methoxy-3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   N-[3-(3-Bromophenylmethoxy)-5-chloro-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   3-[6-Chloro-3-(2,3-dichlorobenzenesulphonylamino)-2-pyrazinyloxymethyl]benzoic acid methyl ester   3-[6-Chloro-3-(2,3-dichlorobenzenesulphonylamino)-2-pyrazinyloxymethyl]benzoic acid   2,3-Dichloro-N-[5-chloro-3-(3-hydroxymethylphenylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(3-methylaminomethylphenylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-{3-([2-hydroxyethylamino]methyl)phenylmethoxy}-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(4-hydroxymethylphenylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-{4-([2-hydroxyethylamino]methyl)phenylmethoxy}-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-(4-hydroxymethylphenylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(2-hydroxymethylphenylmethoxy)-2-pyrazinyl]benzenesulphonamide   5-(2,3-Dichlorobenzenesuphonylamino)-6-methoxypyrazine-2-carboxylic acid, methyl ester   2,3-Dichloro-N-[5-(1-hydroxy-1-methylethyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   N-[5-(2-Aminoethoxy)-3-methoxy-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-{5-[(2-Aminoethyl)thio]-6-chloro-3-methoxy-2-pyrazinyl}-2,3-dichlorobenzenesulfonamide   3-[(5-{[(2,3-Dichlorophenyl)sulphonyl]amino}-6-methoxy-2-pyrazinyl)thio]propanoic acid, methyl ester   2,3-Dichloro-N-[5-bromo-3-methoxy-6-methyl-2-pyrazinyl)benzenesulphonamide   5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-3-methylpyrazine-2-carboxylic acid, methyl ester   2,3-Dichloro-N-[5-(hydroxymethyl)-3-methoxy-6-methyl-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-[5,6-dichloro-3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   3-Chloro-N-(5-chloro-3-methoxy-2-pyrazinyl)-2-fluorobenzenesulphonamide   3-Chloro-2-fluoro-N-[3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   3-{[(2,3-Dichlorophenyl)sulphonyl]amino}pyrazine-2-carboxylic acid, methyl ester   N-(5-Bromo-6-chloro-3-methoxy-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide   3-Chloro-5-{[(2,3-dichlorophenyl)sulphonyl]amino}-6-methoxypyrazine-2-carboxylic acid, methyl ester   2,3-Dichloro-N-[6-chloro-5-(hydroxymethyl)-3-methoxypyrazin-2-yl]benzenesulphonamide   2,3-Dichloro-N-{3-[(6-methoxy-3-pyridinyl)methoxy]-2-pyrazinyl}benzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-methoxy-5-(methoxymethyl)-2-pyrazinyl]benzenesulphonamide   2-Chloro-N-(5-chloro-3-methoxy-2-pyrazinyl)-3-fluorobenzenesulphonamide   2-Chloro-3-fluoro-N-(3-methoxy-2-pyrazinyl)benzenesulphonamide   2-Chloro-3-methoxy-N-(3-methoxy-2-pyrazinyl)benzenesulphonamide   N-[5-Bromo-3-[(25)-2-pyrrolidinylmethoxy]-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   5-(2,3-Dichlorobenzenesulphonylamino)-6-(3-pyridinylmethoxy)pyrazine-2-carboxylic acid, methyl ester   5-{[(2,3-Dichlorophenyl)sulphonyl]amino}-6-(3-pyridinylmethoxy)-2-pyrazinecarboxamide   2,3-Dichloro-N-[5-(4-pyridinyl)-3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-(hydroxymethyl)-3-(3-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-(hydroxymethyl)-3-methoxy)-2-pyrazinyl]benzenesulphonamide   4-Amino-2,3-dichloro-N-(5-chloro-3-methoxy-2-pyrazinyl)benzenesulphonamide   N-(5-Allyloxy-3-methoxy-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[5-(3-hydroxy-1-propynyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   N-{3-[(5-Bromo-3-pyridinyl)methoxy]-5-chloro-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-{[6-(hydroxymethyl)-2-pyridinyl]methoxy}-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-{5-chloro-3-[(2-methyl-4-oxazolyl)methoxy]-2-pyrazinyl}benzenesulphonamide   2,3-Dichloro-N-{3-[(2-methyl-4-oxazolyl)methoxy]-2-pyrazinyl}benzenesulphonamide   N-[5-Bromo-3-(phenylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(2-cyclopropylethoxy)pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(3-thienylmethoxy)pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[(2-methyl-3-furanyl)methoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[(3-furanyl)methoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[(4-fluorophenyl)methoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[(3-fluorophenyl)methoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[3-(2-pyridinyl)propoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(pentyloxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(propyloxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(2-methoxyethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(2-ethoxyethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(2-fluoroethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[2-(1H-imidazol-1-yl)ethoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[3-(3-pyridinyl)propoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-[2-(methylamino)ethoxy]-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-{5-Bromo-3-[3-(4-hydroxyphenyl)propoxy]-2-pyrazinyl}-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(2-phenoxyethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(cyclopropylmethoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[5-Bromo-3-(3-phenoxypropoxy)-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-(5-ethoxy-3-methoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-([1,2,4]-1-triazolyl)-2-pyrazinyl]benzenesulphonamide   2-[5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinylsulphanyl]-N-methylacetamide   2-[5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinylsulphanyl]acetamide   2,3-Dichloro-N-[5-(4-fluorobenzylsulphanyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-cyanomethylsulphanyl-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-([1,2,4]-3-oxadiazolylmethylsulphanyl)-2-pyrazinyl]benzenesulphonamide   N-[5-(2-Aminoethylsulphanyl)-3-methoxy-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-(5-methyl-3-isoxazolylmethoxy))-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-(5-dimethylaminomethyl-2-furanylmethoxy)-3-methoxy-2-pyrazinyl]benzenesulphonamide   N-[5-Bromo-3-(5-dimethylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]-2,3-dichloro-benzenesulphonamide   2,3-Dichloro-N-[5-(2-hydroxyethylsulphanyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-{5-[2-(ethylureido)ethylsulphanyl]-3-methoxy-2-pyrazinyl}benzenesulphonamide   2,3-Dichloro-N-[3-(5-dimethylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-(5-dimethylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[6-chloro-3-(5-methylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(5-dimethylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-(5-methylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]benzenesulphonamide   N-(5-Bromo-3-methoxypyrazinyl)-2-cyanobenzenesulphonamide   N-(5-Bromo-3-methoxypyrazinyl)-2,3-dichloro-4-fluorobenzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-(4-morpholinylmethyl)-2-pyrazinyl]benzenesulphonamide   N-(3-Allyloxy-5-chloro-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(2-propynyloxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[3-(2-propynyloxy)-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-(5-cyano-3-methoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-{3-methoxy-5-[(2S)-pyrrolidin-2-ylmethoxy]-2-pyrazinyl}benzenesulfonamide hydrochloride   2,3-Dichloro-N-{6-chloro-3-methoxy-5-[(2R)-2-pyrrolidinylmethoxy]-2-pyrazinyl}benzenesulphonamide Hydrochloride   2,3-Dichloro-N-[3-methoxy-5-(2-pyridinylmethoxy)-2-pyrazinyl]benzenesulphonamide Hydrochloride   2,3-Dichloro-N-(3-methoxy-6-methyl-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-(1H-1,2,4-triazol-1-ylmethyl)-2-pyrazinyl]benzenesulphonamide   N-(3-(5-Aminomethyl-2-furanylmethoxy)-5-chloro-2-pyrazinyl)-2,3-dichloro-benzenesulphonamide   N-(3-(5-Aminomethyl-2-furanylmethoxy)-2-pyrazinyl)-2,3-dichlorobenzenesulphonamide   2,3-Dichloro-N-[3-methoxy-5-(2-propyn-1-yloxy)-2-pyrazinyl]benzenesulphonamide   {[5-(2,3-Dichlorophenylsulfonylamino)-6-methoxy-2-pyrazinyl]oxy}acetic acid, methyl ester   N-[5-(2,3-Dichlorophenylsulphonylamino)-6-methoxy-2-pyrazinyl]-2-hydroxyacetamide   6-(2,3-Dichlorophenylsulphonylamino)-5-methoxy-2-pyrazinecarboxylic acid, methyl ester   2,3-Dichloro-N-[6-(hydroxymethyl)-3-methoxy-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-(5-methanesulphonyl-3-methoxy-2-pyrazinyl)benzenesulphonamide   2-[5-(2,3-Dichlorobenzenesulphonylamino)-6-methoxy-2-pyrazinyloxy]-N,N-diethyl-acetamide   2,3-Dichloro-N-{5-[2-(dimethylamino)ethylsulphanyl]-3-methoxy-2-pyrazinyl}benzenesulphonamide   2,3-Dichloro-N-(5-difluoromethyl-3-methoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-4-fluoro-N-(3-methoxy-2-pyrazinyl)benzenesulphonamide   2,3-Dichloro-N-{5-chloro-3-[1-(cyclopropyl)ethoxy]-2-pyrazinyl}benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(5-formyl-2-furanylmethoxy)-2-pyrazinyl]benzenesulphonamide   2,3-Dichloro-N-[5-chloro-3-(5-cyclopropylaminomethyl-2-furanylmethoxy)-2-pyrazinyl]-benzenesulphonamide   N-[5,6-bis-(Hydroxymethyl)-3-methoxy-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide   N-[3-[(2-amino-4-oxazolyl)methoxy]-5-chloro-2-pyrazinyl]-2,3-dichlorobenzenesulphonamide and pharmaceutically acceptable salts and solvates thereof.   
   
   
       7 . A process for the preparation of a compound of formula (I) as claimed in  claim 1  which comprises: 
     (a) reaction of a compound of formula (II): 
     
       
         
         
             
             
         
       
       where R 4 , R 5  and R 6  are as defined in  claim 1  or are protected derivatives thereof with a compound of formula (III): 
     
     
       
         
         
             
             
         
       
       where R 1 , R 2  and R 3  are as defined in  claim 1  or are protected derivatives thereof and LG is a leaving group, or 
     
     (b) for compounds where R 4  is C 1-6  alkoxy where the alkyl group may form a 3-6 membered saturated ring or may be substituted with 1-3 fluorine atoms or a cyano group;
 C 3-6  alkenyloxy or C 3-6  alkynyloxy where either may be optionally substituted with hydroxy or NR 14 R 15 ; 
 OC 1-6  alkyl-X—C 1-6  alkyl where the alkyl groups may form a 3-6 membered saturated ring; 
 OC 1-6  alkylR 11 , or OC 2-6  alkyl-X—R 11  where the alkyl group may form a 3-6 membered saturated ring and is optionally substituted with 1-3 groups selected from hydroxy, halogen, NR 14 R 15 , SR 13 , S(O) 2 R 13 , S(O)R 13 ; or 
 OC 1-6  alkylR 16 ; 
 treating a compound of the formula (VI), where LG is a leaving group: 
 
     
       
         
         
             
             
         
       
       with a compound of formula
   R 4 —H  (V) 
 
       (V) in the presence of a suitable base, or 
     
     (c) for compounds of structure (I), where R 5  is an optionally substituted aryl or heteroaryl ring as defined above, reacting a compound of formula (XI) or (VII) where LG is a leaving group with an aryl or heteroaryl boronic acid in the presence of a palladium catalyst and a suitable base at elevated temperature: 
     
       
         
         
             
             
         
       
     
     and optionally thereafter process (a), (b) or (c)
 removing any protecting groups, 
 converting a compound of formula (I) to a further compound of formula (I) 
 forming a pharmaceutically acceptable salt. 
 
   
   
       8 . A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in  claim 1  in association with a pharmaceutically acceptable adjuvant, diluent or carrier. 
   
   
       9 . A process for the preparation of a pharmaceutical composition as claimed in  claim 8  which comprises mixing a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in  claim 1  with a pharmaceutically acceptable adjuvant, diluent or carrier. 
   
   
       10 . (canceled) 
   
   
       11 . A method of treating a chemokine mediated disease wherein the chemokine binds to one or more chemokine receptors, which comprises administering to a patient a therapeutically effective amount of a compound of formula (IB), or a pharmaceutically acceptable salt or solvate thereof: 
     
       
         
         
             
             
         
       
     
     in which:
 R 1 , R 2  and R 3  are independently hydrogen, halogen, cyano, CF 3 , or C 1-6  alkyl; 
 R 4  is halogen, CO 2 R 12 ,
 C 1-6  alkoxy where the alkyl group may form a 3-6 membered saturated ring or may be substituted with 1-3 fluorine atoms or a cyano group; 
 C 3-6  alkenyloxy or C 3-6  alkynyloxy where either may be optionally substituted with hydroxy or NR 14 R 15 ; 
 OC 1-6  alkyl-X—C 1-6  alkyl where the alkyl groups may form a 3-6 membered saturated ring; 
 OC 1-6  alkylR 11 , or OC 2-6  alkyl-X—R 11  where the alkyl group may form a 3-6 membered saturated ring and is optionally substituted with 1-3 groups selected from hydroxy, halogen, NR 14 R 15 , SR 13 , S(O) 2 R 13 , S(O)R 13 ; 
 OC 1-6  alkylR 16 ; 
 
 R 5  and R 6  are independently hydrogen, cyano, halogen, CO2R 12 , CONR 14 R 15 ;
 C 1-6  alkyl optionally substituted by hydroxy, NR 14 R 15 , or 1-3 fluorines; 
 C 1-6  alkylR 11  or XCH(R 11 )C 1-6  alkyl or XCH(R 16 )C 1-6  alkyl where the alkyl group may be optionally substituted with 1-3 groups selected from hydroxy, and NR 14 R 15 ; 
 NR 14 R 15 ; N(R 11 )R 11 ; X—(CH 2 )qNR 14 R 15 ; (CH 2 )nNR 14 R 15 ; 
 C 3-6  alkynyl or C 3-6  alkenyl optionally branched and optionally substituted with 1-3 groups selected from hydroxy, cyano, halogen and ═O; 
 R 11 ; X—R 11 ; X—R 12 ; X—C 1-6  alkylR 16 ; X—R 16 ; X—(CH 2 )nCO 2 R 12 ; X—(CH 2 )nCONR 14 R 15 ; 
 X—(CH 2 )nR 11 ; X—(CH 2 )nCN; X—(CH 2 )qOR 12 ; (CH 2 )nOR 12 ; 
 (CH 2 )n-X—R 11 ; X—(CH 2 )qNHC(O)NHR 12 ; X—(CH 2 )qNHC(O)R 12 ; 
 X—(CH 2 )qNHS(O) 2 R 12 ; X—(CH 2 )qNHS(O) 2 R 11 ; X—C 3-6  alkenyl; X—C 3-6  alkynyl; 
 
 n is 1, 2, 3, 4 or 5; 
 q is 2, 3, 4, 5 or 6; 
 X is NR 13 , O, S, S(O), S(O) 2 ; 
 R 11  is an aryl group or a 5-7 membered heteraromatic ring containing 1-4 heteroatoms selected from nitrogen, oxygen or sulphur each of which can be optionally substituted by 1-3 groups selected from halogen, C(O)NR 14 R 15 , C(O)OR 12 , hydroxy, ═O, ═S, CN, NO 2  NR 14 R 15 , X(CH 2 )qNR 14 R 15 , (CH 2 )nNR 14 R 15 , (CH 2 )nOH, SR 13 , S(O)R 13 , S(O) 2 R 13 C 1-6  alkyl-X—C 1-6  alkyl, C 1-6  alkyl or C 1-6  alkoxy where the alkyl group may form a 3-6 membered ring or is optionally substituted with 1-3 groups selected from hydroxy, halogen, NR 14 R 15 , SR 13 , S(O)R 13 , S(O) 2 R 13 ; 
 R 12  and R 13  are independently hydrogen or C 1-6  alkyl where the alkyl group may be substituted with 1-3 fluorine atoms or may form a saturated 3-6 membered ring; 
 R 11  and R 15  are independently hydrogen, C 1-6  alkyl, C 3-6  cycloalkyl or (CH 2 )qOH, 
 or R 14  and R 15  together with the nitrogen atom to which they are attached form a 4-8 membered saturated ring containing 1-3 heteroatoms selected from nitrogen, oxygen and sulphur and optionally substituted by C 1-6  alkyl, C 1-6  alkyl-OH, or hydroxy; and 
 R 16  is a 4-8 membered saturated ring containing 1-3 heteroatoms selected from nitrogen, oxygen or sulphur and optionally substituted with 1-3 groups selected from hydroxy, cyano, halogen and ═O, 
 
   
   
       12 . The method according to  claim 11  in which the chemokine receptor belongs to the CCR chemokine receptor subfamily. 
   
   
       13 . The method according to  claim 11  in which the chemokine receptor is the CCR4 receptor. 
   
   
       14 . A method of treating an inflammatory disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (IB), or a pharmaceutically acceptable salt or solvate thereof, as defined in  claim 11 . 
   
   
       15 . The method according to  claim 14 , wherein the disease is asthma.