Novel Compounds

Abstract

The invention relates to thiophene carboxamides of formula (I), wherein A, R 1 , R 2 , R 3 , n and X are as defined in the specification, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       in which:
 R 1  represents NH 2  or R 1  represents a methyl group optionally substituted by one or more groups selected independently from C 1 -C 4  alkyl, C 3 -C 6  cycloalkyl, halogen, hydroxyl, C 1 -C 4  alkoxy, S(O) v CH 3  and NR 4 R 5 ; 
 X represents O or S; 
 R 2  represents hydrogen, halogen, cyano, nitro, —NR 6 R 7 , —CONR 6 R 7 , —COOR 6 , —NR 6 COR 7 , —S(O) m R 6 , —SO 2 NR 6 R 7 , —NR 6 SO 2  R 7 , C 1 -C 2  alkyl, trifluoromethyl, C 2 -C 3  alkenyl, C 2 -C 3  alkynyl, trifluoromethoxy, C 1 -C 2  alkoxy or C 1 -C 2  alkanoyl; 
 A represents a phenyl ring; said phenyl ring being optionally substituted by one or more substituents selected independently from halogen, cyano, nitro, —NR 8 R 9 , —CONR 8 R 9 , —COOR 8 , —NR 8 COR 9 , —S(O) s R 8 , —SO 2 NR 8 R 9 , —NR 8 SO 2 R 9 , C 1 -C 6  alkyl, trifluoromethyl, —(CH 2 ) t R 10 , —O(CH 2 ) t R 11  or —OR 12 ; 
 n represents an integer 1 or 2; and when n represents 2, each R 3  group may be selected independently; 
 R 3  represents a group —W—Y—Z wherein: 
 W represents O, S(O) r , NR 13 , CH 2 , —CH 2 —O— or a bond; 
 Y represents a bond or a group —(CH 2 ) p -T-(CH 2 ) q — wherein p and q independently represent an integer 0, 1 or 2; and T represents O, —CO— or CR 14 R 15 ; 
 R 14  and R 15  independently represent H, CH 3  or F; 
 or R 14  represents H or CH 3  and R 15  represents hydroxyl or OCH 3 ; 
 or the group CR 14 R 15  together represents a C 3 -C 6  cycloalkyl ring; 
 Z represents: 
 (a) a phenyl ring or a 5- or 6-membered heteroaromatic ring containing one to three heteroatoms selected independently from O, N and S; said phenyl or heteroaromatic ring being optionally substituted by one or more substituents selected independently from halogen, cyano, —NR 16 R 17 , —CONR 16 R 17 , —COOR 16 , —COR 16  —NR 16 COR 17 , —S(O) u R 16 , —SO 2 NR 16 R 17 , —NR 16 SO 2 R 17 , hydroxyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkyl and C 1 -C 6  alkoxy; said alkyl or alkoxy group being optionally further substituted by one or more groups selected from halogen, cyano, hydroxyl, C 1 -C 4  alkoxy and NR 18 R 19 ; or 
 (b) a 3- to 8-membered saturated or partially unsaturated monocyclic or saturated bicyclic ring system optionally incorporating one or two heteroatoms selected independently from O, N and S, and optionally incorporating a carbonyl group; said ring system being optionally substituted by one or more substituents selected independently from halogen, cyano, —NR 16 R 17 , —CONR 16 R 17 , —COOR 16 , —COR 16 , —NR 16 COR 17 , —S(O) u R 16 —SO 2 NR 16 R 17 , —NR 16 SO 2 R 17 , hydroxyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkyl, C 3 -C 6  cycloalkyl and C 1 -C 6  alkoxy; said alkyl or alkoxy group being optionally further substituted by one or more groups selected from halogen, cyano, hydroxyl, C 3 -C 6  cycloalkyl, C 1 -C 4  alkoxy and NR 18 R 19 ; provided that said saturated monocyclic ring Z is not bonded to Y through nitrogen if the group —W—Y— represents —(CH 2 ) 2-4 — or —O—(CH 2 ) 2-4 — when the saturated ring Z is also unsubstituted; or 
 (c) if W represents O, then Z may also represent hydroxyl, OCH 3 , CF 3 , CHF 2  or CH 2 F, provided that the group —Y—Z does not thereby represent —O—(CH 2 ) 2-4 —OCH 3 ; 
 R 10  and R 11  independently represent NR 20 R 21  where R 20  and R 21  are independently hydrogen or C 1 -C 6  alkyl optionally substituted by C 1 -C 4  alkoxy; or the group NR 20 R 21  represents a 5- or 6-membered saturated azacyclic ring optionally containing a further O, S or NR 22  group; where R 22  is hydrogen or C 1 -C 6  alkyl; or R 10  and R 11  independently represent C 1 -C 6  alkoxy; 
 R 4  and R 5  independently represent H or C 1 -C 4  alkyl; or the group NR 4 R 5  represents a 5- or 6-membered saturated azacyclic ring optionally containing a further O, S or NR 23  group; where R 23  is hydrogen or C 1 -C 4  alkyl; 
 R 6  and R 7  independently represent H or C 1 -C 2  alkyl; 
 R 8 , R 9  and R 12  independently represent H or C 1 -C 6  alkyl; 
 R 13  represents H or C 1 -C 4  alkyl; 
 R 16  and R 17  independently represent H or C 1 -C 6  alkyl optionally substituted by OH, C 1 -C 4  alkoxy or one or more fluoro atoms; or the group NR 16 R 17  represents a 5- or 6-membered saturated azacyclic ring optionally containing a further O, S or NR 24  group; where R 24  is hydrogen or C 1 -C 6  alkyl optionally substituted by OH, C 1 -C 4  alkoxy or one or more fluoro atoms; 
 R 18  and R 19  independently represent H or C 1 -C 4  alkyl; or the group NR 18 R 19  represents a 5- or 6-membered saturated azacyclic ring optionally containing a further O, S or NR 25  group; where R 25  is hydrogen or C 1 -C 4  alkyl; 
 m, r, s, u and v independently represent an integer 0, 1 or 2; 
 t represents an integer 2, 3 or 4; 
 and pharmaceutically acceptable salts thereof: 
 with the proviso that the following two compounds are excluded: 
 2-[(aminocarbonyl)amino]-5-(4-[2-(1-(2,2,6,6-tetramethyl)piperidinyl)ethoxy]phenyl)-3-thiophenecarboxamide; 
 2-[(aminocarbonyl)amino]-5-(4-(thiazol-4-yl-methoxy)phenyl)-3-thiophenecarboxamide. 
 
     
     
         2 . A compound of formula (I), according to  claim 1 , wherein X represents oxygen. 
     
     
         3 . A compound of formula (I), according to  claim 1 , wherein R 1  represents NH 2 . 
     
     
         4 . (canceled) 
     
     
         5 . A compound of formula (I), according to  claim 1 , in which R 2  represents H. 
     
     
         6 . A compound of formula (I), according to  claim 1 , in which W represents O, CH 2  or a bond. 
     
     
         7 . A compound of formula (I), according to  claim 1 , selected from:
 2-[(aminocarbonyl)amino]-4-methyl-5-(4-biphenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-(4-[(3,5-dimethylisoxazol-4-yl)methoxy]phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-(4-[(4-chlorophenyl)methoxy]phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-(4-[(5-chlorothien-2-yl)methoxy]phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-{-4-[2-(2,2,6,6-tetramethylpiperidin-1-yl)ethoxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-(4-[(thiazol-4-yl)methoxy]phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-(4-[(1,2,5-thiadiazol-3-yl)methoxy]phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-(4-[(1-methylperhydroazepin-3-yl)oxy]phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{3-[6-(piperidin-4-yloxy)]-pyridine}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-(4-[1,3,4-oxadiazol-2-yl]-2-phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-(4-cyclopropylmethoxyphenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[3-(1,3-thiazol-4-ylmethoxy)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(morpholin-4-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{2-benzyloxyphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-(4-fluorophenylmethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-(2-[4-fluorophenyl]ethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-(2-[4-chlorophenyl]ethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-(2-phenylethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{4-chlorophenylmethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[2-(N-morpholinyl)]ethylthio)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[2-(N-pyrrolidinyl)]ethylthio)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[2-(N-piperidinyl)]ethylthio)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[4-(pyrrolidinyl)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[4-(piperidinyl)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[4-(N-imidazolyl)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5{4-[2-(2-methoxyethoxy)ethoxy]-phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{4-[2-(cyclopropylmethoxy)ethoxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{3-chloro-4-(tetrahydrofuran-2-ylmethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{4-(tetrahydrofuran-2-ylmethoxy)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5{4-[2-(2-methoxyethoxy)ethoxy]-3-methylphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{3-chloro-4-[2-(2-methoxyethoxy)ethoxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-(4-methylpiperazinylmethyl)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-(4-isopropylpiperazinylmethyl)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-(4-t-butyloxycarbonylpiperazinylmethyl)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[4-(pyrrolidinylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[2-(2-(4,4-difluoropiperidin-1-yl)ethoxy)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-(2-(3,3-difluoropyrrolidin-1-yl)ethoxy)phenyl]-3-thiophenecarboxamide;   3-[(aminocarbonyl)amino]-5-[4-(morpholin-4-ylmethyl)phenyl]thiophene-2-carboxamide;   3-[(aminocarbonyl)amino]-5-[4-(cis-2,6-dimethylmorpholin-4-ylmethyl)phenyl]thiophene-2-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(cis-2,6-dimethylmorpholin-4-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[3-(morpholin-4-ylmethyl)-4-isobutoxyphenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[3-(morpholin-4-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-(4-{[2-(methoxymethyl)morpholin-4-yl]methyl}phenyl)thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[3-chloro-4-(morpholin-4-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{4-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(1-{piperidin-1-yl}ethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{4-[(1R)-1-morpholin-4-ylethyl]phenyl}thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-(4-{[4-(2-methoxyethyl)piperazin-1-yl]methyl}phenyl)thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(piperidin-1-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-ylmethyl]phenyl}thiophene-3-carboxamide;   5-{4-[(4-acetylpiperazin-1-yl)methyl]phenyl}-2-[(aminocarbonyl)amino]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(1,4-oxazepan-4-ylmethyl)phenyl]thiophene-3-carboxamide;   (1S)-2-((aminocarbonyl)amino)-5-(4-(1-{morpholin-4-yl}ethyl)phenyl)thiophene-3-carboxamide;   2-((aminocarbonyl)amino)-5-(4-(1-methyl-1-{morpholin-4-yl}ethyl)phenyl)thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-((4-methylpiperazin-1-yl)methyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-((2-ethoxycarbonylpiperidin-1-yl)methyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-((3-diethylaminocarbonylpiperidin-1-yl)methyl)phenyl]-thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-((3-hydroxypyrrolidin-1-yl)methyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-({(2-hydroxyethyl)piperazin-1-yl}methyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-4-methyl-5-{4-[4-morpholino]methylphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[4-((4-hydroxypiperidin-1-yl)methyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-(2-piperazin-1-ylphenyl)thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[2-(4-methylpiperazin-1-yl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{2-[3-methylamino)pyrrolidin-1-yl]phenyl}thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(cyclopentyloxy)-2-(2-{piperidin-1-yl}ethoxy)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[2-(2-{piperidin-1-yl}ethoxy)-4-pyrrolidin-1-ylphenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-piperidin-1-yl-2-(2-{piperidin-1-yl}ethoxy)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(morpholin-4-ylmethyl)-2-(2-{piperidin-1-yl}ethoxy)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(2-methoxyethoxy)-2-(2-piperidin-1-ylethoxy)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-morpholin-4-yl-2-(2-piperidin-1-ylethoxy)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[2-(2-hydroxyethoxy)phenyl]thiophene-3-carboxamide;   (3R)-2-[(aminocarbonyl)amino]-5-{2-[tetrahydrofuran-3-yloxy]phenyl}-3-thiophenecarboxamide;   (3S)-2-[(aminocarbonyl)amino]-5-{2-[tetrahydrofuran-3-yloxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(tetrahydropyran-4-yloxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[cyclopropylmethoxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[cyclopentyloxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-ethylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-tert-butyloxycarbonyl-3-pyrrolidinyl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-methylpiperidin-2-yl)methoxy]phenyl}-3-thiophenecarboxamide;   (2S)-2-[(aminocarbonyl)amino]-5-(2-{[1-methylpyrrolidin-2-yl]methoxy}phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-(2-{[1-(2-methoxyethyl)pyrrolidin-3-yl]oxy}phenyl)-3-thiophenecarboxamide;   (2R)-2-[(aminocarbonyl)amino]-5-(2-{[1-methylpyrrolidin-2-yl]methoxy}phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-(2-(2,2,6-trimethylpiperidin-1-yl)ethoxy)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{5-chloro-2-[(1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{4-fluoro-2-[(1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{4,5-difluoro-2-[1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-5-methylphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{5-cyano-2-[(1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-5-methoxyphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{3,5-difluoro-2-[(1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-3-methoxyphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-5-trifluoromethylphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-4-trifluoromethylphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-4-methoxyphenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{5-fluoro-2-[(1-isopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-isopropylpyrrolidin-3-yl)oxy]-3-(morpholin-4-ylmethyl)phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-(2-{[(1-(cyclopropylmethyl)pyrrolidin-3-yl]oxy}phenyl)-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-cyclopropylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(2-(4-fluoropiperidin-1-yl)ethoxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-methylpiperidin-4-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1-methylpyrrolidin-3-yl)oxy]phenyl}-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[4-(2-{morpholin-4-yl}acetyl)phenyl]3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-{2-(4-hydroxy-1-piperidinyl)ethoxy}phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-[2-(2-(2,2,6,6-tetramethylpiperidin-1-yl)ethoxy)phenyl]-3-thiophenecarboxamide;   2-[(aminocarbonyl)amino]-5-{2-[2-(3-pyrrolin-1-yl)ethoxy]phenyl}thiophene-3-carboxamide;   cis/trans-2-[(aminocarbonyl)amino]-5-{2-[2-(2,5-dimethyl-3-pyrrolin-1-yl)ethoxy]phenylthiophene-3-carboxamide;   (2S)-2-[(aminocarbonyl)amino]-5-[4-(2-methoxymethylpyrrolidin-1-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(4-aminocarbonylpiperidin-1-ylmethyl)phenylthiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(3-hydroxymethylpiperidin-1-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[4-(4-hydroxymethylpiperidin-1-ylmethyl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-[2-(3-{morpholin-4-yl}pyrrolidin-1-yl)phenyl]thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{2-[4-(2-methoxyethyl)piperazin-1-yl]phenyl}thiophene-3-carboxamide;   2-[(aminocarbonyl)amino]-5-{2-[(1S,4S)-2,5-diazabicyclobicyclo[2.2.1]hept-2-yl]phenyl}thiophene-3-carboxamide;   and pharmaceutically acceptable salts thereof.   
     
     
         8 . A process for the preparation of a compound of formula (I), according to  claim 1 , which comprises:
 (a) reaction of a compound of formula (II):   
       
         
           
           
               
               
           
         
       
       wherein A, R 2 , R 3  and n are as defined in  claim 1  with an isocyanate or an isothiocyanate or an acyl derivative, R 1 —CO-L where L is a leaving group; or
 (b) reaction of compound of formula (III) 
 
       
         
           
           
               
               
           
         
       
       wherein R 3 , n and A are as defined in  claim 1 ,
 with a compound of formula (IV) 
 
       
         
           
           
               
               
           
         
       
       wherein X, R 1  and R 2  are as defined in  claim 1  and LG represents a leaving group; or
 (c) reaction of compound of formula (V) 
 
       
         
           
           
               
               
           
         
       
       wherein R 3 , n and A are as defined in  claim 1  and LG represents a leaving group,
 with a compound of formula (VI) 
 
       
         
           
           
               
               
           
         
       
       wherein X, R 1  and R 2  are as defined in  claim 1 ;
 and where necessary converting the resultant compound of formula (I), or another salt thereof, into a pharmaceutically acceptable salt thereof; or converting the resultant compound of formula (I) into a further compound of formula (I); and where desired converting the resultant compound of formula (I) into an optical isomer thereof. 
 
     
     
         9 . 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. 
     
     
         10 . A process for the preparation of a pharmaceutical composition which comprises mixing a compound of formula (I), or a pharmaceutically acceptable salt thereof, as claimed in  claim 1  with a pharmaceutically acceptable adjuvant, diluent or carrier. 
     
     
         11 - 12 . (canceled) 
     
     
         13 . A method of treatment or prophylaxis of an inflammatory disease, the method comprising administering to a person suffering from, or at risk of, said disease a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof; as claimed in  claim 1 . 
     
     
         14 . The method as claimed in  claim 13  wherein the inflammatory disease is asthma. 
     
     
         15 . The method as claimed in  claim 13  wherein the inflammatory disease is rheumatoid arthritis. 
     
     
         16 . The method as claimed in  claim 13  wherein the inflammatory disease is multiple sclerosis. 
     
     
         17 . The method as claimed in  claim 13  wherein the inflammatory disease is chronic obstructive pulmonary disease. 
     
     
         18 . The method as claimed in  claim 13  wherein the inflammatory disease is cancer. 
     
     
         19 . A method of treating, or reducing the risk of, diseases or conditions in which inhibition of IKK2 activity is beneficial which comprises administering to a person suffering from or at risk of said disease or condition a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof, as claimed in  claim 1 .