Amide derivatives bearing a cyclopropylaminoacarbonyl substituent useful as cytokine inhibitors

Abstract

The invention concerns a compound of the Formula (I), wherein Qa is heteroaryl and is substituted with halogeno; R1 and R2 are hydrogen; and Qb is phenyl or heteroaryl, and Qb may optionally bear 1 or 2 substituents selected from hydroxy, halogeno and (1-6C)alkyl, or a pharmaceutically-acceptable salt thereof; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of diseases or medical conditions mediated by cytokines.

1 . A compound of the Formula I 
       
         
           
           
               
               
           
         
         wherein 
         Q a  is phenyl or heteroaryl, and Q a  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, trifluoromethyl, cyano, amino, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl]amino and (1-6C)alkoxycarbonyl; 
         R 1  and R 2  are each independently selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl and (2-6C)alkynyl; and 
         Q b  is phenyl, heteroaryl or heterocyclyl, and Q b  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxy, (3-6C)cycloalkoxy, (3-6C)cycloalkyl-(1-6C)alkoxy, carboxy, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, aminosulphonyl,  N -(1-6C)alkylsulphamoyl,  N , N -di-[(1-6C)alkyl]sulphamoyl and (3-6C)cycloalkylsulphonyl; 
         and wherein any of the substituents on Q a  or Q b  defined hereinbefore which comprise a CH 2  group which is attached to 2 carbon atoms or a CH 3  group which is attached to a carbon atom may optionally bear on each said CH 2  or CH 3  group one or more substituents selected from hydroxy, cyano, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; 
         or a pharmaceutically-acceptable salt thereof. 
       
     
     
         2 . A compound of the Formula I according to  claim 1  wherein
 Q a  is phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, and Q a  may optionally bear 1 or 2 substituents selected from halogeno, (1-6C)alkyl and (1-6C)alkoxy; 
 R 1  and R 2  are each independently selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl and (2-6C)alkynyl; and 
 Q b  is phenyl, heteroaryl or heterocyclyl, and Q b  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxy, (3-6C)cycloalkoxy, (3-6C)cycloalkyl-(1-6C)alkoxy, carboxy, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, aminosulphonyl,  N -(1-6C)alkylsulphamoyl,  N , N -di-[(1-6C)alkyl]sulphamoyl and (3-6C)cycloalkylsulphonyl; 
 and wherein any of the substituents on Q a  or Q b  defined hereinbefore which comprise a CH 2  group which is attached to 2 carbon atoms or a CH 3  group which is attached to a carbon atom may optionally bear on each said CH 2  or CH 3  group one or more substituents selected from hydroxy, cyano, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; 
 or a pharmaceutically-acceptable salt thereof. 
 
     
     
         3 . A compound of the Formula I according to  claim 1  or  claim 2  wherein
 Q a  is phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, and Q a  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (1-6C)alkyl and (1-6C)alkoxy; or a pharmaceutically-acceptable salt thereof. 
 
     
     
         4 . A compound of the Formula I according to  claim 1  or  claim 2  wherein
 Q b  is phenyl or heteroaryl, and Q b  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxy, (3-6C)cycloalkoxy, (3-6C)cycloalkyl-(1-6C)alkoxy, carboxy, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, aminosulphonyl,  N -(1-6C)alkylsulphamoyl,  N , N -di-[(1-6C)alkyl]sulphamoyl and (3-6C)cycloalkylsulphonyl;
 and wherein any of the substituents on Q b  which comprise a CH 2  group which is attached to 2 carbon atoms or a CH 3  group which is attached to a carbon atom may optionally bear on each said CH 2  or CH 3  group one or more substituents selected from hydroxy, cyano, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; or a pharmaceutically-acceptable salt thereof. 
 
 
     
     
         5 . A compound of the Formula I according to  claim 1  or  claim 2  wherein Q b  is phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiazolyl, thiadiazolyl, imidazolyl, isoxazolyl, oxazolyl, furanyl, thienyl, benzimidazolyl, isoquinolinyl, quinolinyl, benzothiazolyl or pyrido[1,2-a]imidazolyl, and Q b  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxy, (3-6C)cycloalkoxy, (3-6C)cycloalkyl-(1-6C)alkoxy, carboxy, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, aminosulphonyl,  N -(1-6C)alkylsulphamoyl,  N , N -di-[(1-6C)alkyl]sulphamoyl and (3-6C)cycloalkylsulphonyl;
 and wherein any of the substituents on Q b  which comprise a CH 2  group which is attached to 2 carbon atoms or a CH 3  group which is attached to a carbon atom may optionally bear on each said CH 2  or CH 3  group one or more substituents selected from hydroxy, cyano, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; or a pharmaceutically-acceptable salt thereof. 
 
     
     
         6 . A compound of the Formula I according to  claim 1  or  claim 2  wherein R 1  and R 2  are each independently selected from hydrogen, (1-6C)alkyl, (2-6C)alkenyl and (2-6C)alkynyl; or a pharmaceutically-acceptable salt thereof. 
     
     
         7 . A compound of the Formula I according to  claim 1  or  claim 2  wherein R 1  and R 2  are each independently selected from hydrogen and (1-6C)alkyl; or a pharmaceutically-acceptable salt thereof. 
     
     
         8 . A compound of the Formula I according to Claim  1  wherein
 Q a  is phenyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, and Q a  may optionally bear 1 or 2 substituents selected from halogeno, (1-6C)alkyl and (1-6C)alkoxy; 
 R 1  and R 2  are each independently selected from hydrogen and (1-6C)alkyl; and 
 Q b  is phenyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, thiazolyl, thiadiazolyl, imidazolyl, isoxazolyl, oxazolyl, furanyl, thienyl, benzimidazolyl, isoquinolinyl, quinolinyl, benzothiazolyl or pyrido[1,2-a]imidazolyl, and Q b  may optionally bear 1 or 2 substituents selected from hydroxy, halogeno, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxy, (3-6C)cycloalkoxy, (3-6C)cycloalkyl-(1-6C)alkoxy, carboxy, (1-6C)alkoxycarbonyl,  N -(1-6C)alkylcarbamoyl,  N , N -di-[(1-6C)alkyl]carbamoyl, (2-6C)alkanoyl, amino, (1-6C)alkylamino, di-[(1-6C)alkyl]amino, halogeno-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, amino-(1-6C)alkyl, (1-6C)alkylamino-(1-6C)alkyl, di-[(1-6C)alkyl]amino-(1-6C)alkyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, aminosulphonyl,  N -(1-6C)alkylsulphamoyl,  N , N -di-[(1-6C)alkyl]sulphamoyl and (3-6C)cycloalkylsulphonyl; 
 and wherein any of the substituents on Q b  which comprise a CH 2  group which is attached to 2 carbon atoms or a CH 3  group which is attached to a carbon atom may optionally bear on each said CH 2  or CH 3  group one or more substituents selected from hydroxy, cyano, amino, (1-6C)alkyl, (1-6C)alkoxy, (1-6C)alkylamino and di-[(1-6C)alkyl]amino; or a pharmaceutically-acceptable salt thereof. 
 
     
     
         9 . A compound of the Formula I according to  claim 1  or  claim 2  selected from:—
 3-{[4-(benzyloxy)benzoyl]amino}- N -cyclopropyl-4-methylbenzamide; 
 3-{[3-(benzyloxy)benzoyl]amino}- N -cyclopropyl-4-methylbenzamide; 
 4-(benzyloxy)- N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-methylbenzamide; 
 4-(benzyloxy)-3-fluoro- N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}benzamide; 
 4-(benzyloxy)-3-chloro- N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}benzamide; 
   N -cyclopropyl-4-methyl-3-{[4-(pyridin-2-ylmethoxy)benzoyl]amino}benzamide; 
   N -cyclopropyl-4-methyl-3-{[4-(1,3-thiazol-4-ylmethoxy)benzoyl]amino}benzamide; 
   N -cyclopropyl-4-methyl-3-{[4-(pyridin-3-ylmethoxy)benzoyl]amino}benzamide; 
   N -cyclopropyl-4-methyl-3-({4-[(5-methylisoxazol-3-yl)methoxy]benzoyl}amino)benzamide; 
 3-({4-[(5-chloro-1,2,3-thiadiazol-4-yl)methoxy]benzoyl}amino)- N -cyclopropyl-4-methylbenzamide; 
   N -cyclopropyl-3-{[4-(imidazo[1,2-a]pyridin-2-ylmethoxy)benzoyl]amino}-4-methylbenzamide; 
   N -cyclopropyl-4-methyl-3-({4-[(2-methyl-1,3-thiazol-4-yl)methoxy]benzoyl}amino)benzamide; 
   N -cyclopropyl-3-({4-[(3,5-dimethylisoxazol-4-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
   N -cyclopropyl-4-methyl-3-{[4-(1,2,5-thiadiazol-3-ylmethoxy)benzoyl]amino}benzamide; 
 methyl 5-({4-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]phenoxy}methyl)-2-furoate; 
 3-({4-[(2-chloro-1,3-thiazol-5-yl)methoxy]benzoyl}amino)- N -cyclopropyl-4-methylbenzamide; 
 4-(benzyloxy)- N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-methoxybenzamide; 
   N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-methoxy-4-(pyridin-2-ylmethoxy)benzamide; 
   N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-methoxy-4-(1,3-thiazol-4-ylmethoxy)benzamide; 
   N -cyclopropyl-4-methyl-3-{[3-methyl-4-(pyridin-2-ylmethoxy)benzoyl]amino}benzamide; 
   N -cyclopropyl-4-methyl-3-{[3-methyl-4-(1,3-thiazol-4-ylmethoxy)benzoyl]amino}benzamide; 
   N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-fluoro-4-(pyridin-2-ylmethoxy)benzamide; 
   N -{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-fluoro-4-[(2-methyl-1,3-thiazol-4-yl) methoxy]benzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-[(3,5-dimethylisoxazol-4-yl)methoxy]-3-fluorobenzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-fluoro-4-(1,2,5-thiadiazol-3-ylmethoxy)benzamide; 
 N-cyclopropyl-4-methyl-3-{[3-(1,3-thiazol-4-ylmethoxy)benzoyl]amino}benzamide; 
 N-cyclopropyl-4-methyl-3-({3-[(2-methyl-1,3-thiazol-4-yl)methoxy]benzoyl}amino)benzamide; 
 N-cyclopropyl-4-methyl-3-{[3-(pyridin-2-ylmethoxy)benzoyl]amino}benzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-fluoro-4-(1,3-thiazol-4-ylmethoxy)benzamide; 
 N-cyclopropyl-4-methyl-3-({3-methyl-4-[(2-methyl-1,3-thiazol-4-yl)methoxy]benzoyl}amino)benzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-[(3,5-dimethylisoxazol-4-yl)methoxy]-3-methylbenzamide; 
 N-cyclopropyl-4-methyl-3-{[3-methyl-4-(1,2,5-thiadiazol-3-ylmethoxy)benzoyl]amino}benzamide; 
 methyl 5-({4-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]-2-methylphenoxy}methyl)-2-furoate; 
 3-chloro-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-(pyridin-2-ylmethoxy)benzamide; 
 3-chloro-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-4-(1,3-thiazol-4-ylmethoxy)benzamide; 
 N-cyclopropyl-3-({3-[(3,5-dimethylisoxazol-4-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 N-cyclopropyl-4-methyl-3-{[3-(1,2,5-thiadiazol-3-ylmethoxy)benzoyl]amino}benzamide; 
 3-({3-[(2-chloro-1,3-thiazol-5-yl)methoxy]benzoyl}amino)-N-cyclopropyl-4-methylbenzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3-fluoro-4-(imidazo[1,2-a]pyridin-2-ylmethoxy)benzamide; 
 N-cyclopropyl-3-({4-[(4-methoxypyridin-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 N-cyclopropyl-4-methyl-3-{[4-(1-pyridin-2-ylethoxy)benzoyl]amino}benzamide; 
 N-cyclopropyl-3-({3-[(4-methoxypyridin-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 N-cyclopropyl-3-[(4-{[5-(hydroxymethyl)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide; 
 N-cyclopropyl-3-[(4-{[5-(1-hydroxy-1-methylethyl)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide; 
 N-cyclopropyl-3-{[4-({5-[(isopropylamino)methyl]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide; 
 N-cyclopropyl-3-{[4-({5-[(dimethylamino)methyl]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide; 
 methyl 6-({4-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]phenoxy}methyl)nicotinate; 
 N-cyclopropyl-3-{[4-({5-[2-(dimethylamino)ethoxy]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide; 
 N-cyclopropyl-3-[(4-{[5-(1,3-dioxolan-2-ylmethoxy)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide; 
 N-cyclopropyl-3-({4-[(5-hydroxypyridin-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide methyl 6-({4-[({5-[(cyclopropylamino)carbonyl]-2-methylphenyl}amino)carbonyl]phenoxy}methyl)pyridine-2-carboxylate; 
 N-cyclopropyl-3-[(4-{[6-(hydroxymethyl)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide; 
 N-cyclopropyl-3-[(4-{[6-(1-hydroxy-1-methylethyl)pyridin-2-yl]methoxy}benzoyl)amino]-4-methylbenzamide; 
 N-cyclopropyl-3-({4-[(6-{[2-(diethylamino)ethoxy]methyl}pyridin-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 N-cyclopropyl-3-({4-[(6-{[2-(dimethylamino)ethoxy]methyl}pyridin-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 N-cyclopropyl-4-methyl-3-({4-[(1-oxidopyridin-2-yl)methoxy]benzoyl}amino)benzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(imidazo[1,2-a]pyridin-2-ylmethoxy)pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(1,3-thiazol-2-ylmethoxy)pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(pyrimidin-2-ylmethoxy)pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-[(1-methyl-1H-imidazol-2-yl)methoxy]pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-[(1,5-dimethyl-1H-pyrazol-3-yl)methoxy]pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-[(1,3-dimethyl-1H-pyrazol-5-yl)methoxy]pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-[(3-methylpyridin-2-yl)methoxy]pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-[(1-methyl-1H-benzimidazol-2-yl)methoxy]pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(isoquinolin-1-ylmethoxy)pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(quinolin-2-ylmethoxy)pyrimidine-5-carboxamide; 
 2-(1,3-benzothiazol-2-ylmethoxy)-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(1-pyridin-2-ylethoxy)pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(1,3-thiazol-4-ylmethoxy)pyrimidine-5-carboxamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-2-(pyridin-2-ylmethoxy)pyrimidine-5-carboxamide; 
 N-cyclopropyl-3-({4-[(5-cyclopropyl-1,3,4-thiadiazol-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-6-(pyridin-2-ylmethoxy)nicotinamide; 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-(pyridin-2-ylmethoxy)pyrazine-2-carboxamide; 
 3-({4-[(6-bromopyridin-2-yl)methoxy]benzoyl}amino)-N-cyclopropyl-4-methylbenzamide 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-3,5-difluoro-4-(pyridin-2-ylmethoxy)benzamide; 
 N-cyclopropyl-4-methyl-3-({4-[(6-methylpyridin-2-yl)methoxy]benzoyl}amino)benzamide; 
 N-cyclopropyl-4-methyl-3-({4-[(3-methylpyridin-2-yl)methoxy]benzoyl}amino)benzamide; 
 N-cyclopropyl-4-methyl-3-{[4-(pyrimidin-2-ylmethoxy)benzoyl]amino}benzamide; 
 N-cyclopropyl-4-methyl-3-{[4-(pyridazin-3-ylmethoxy)benzoyl]amino}benzamide; 
 N-cyclopropyl-3-{[4-({6-[(2-methoxyethyl)amino]pyridin-2-yl}methoxy)benzoyl]amino}-4-methylbenzamide; 
 N-cyclopropyl-3-({4-[(6-{[2-(dimethylamino)ethyl]amino}pyridin-2-yl)methoxy]benzoyl}amino)-4-methylbenzamide; 
 5-(benzyloxy)-N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}pyridine-2-carboxamide 
 N-{5-[(cyclopropylamino)carbonyl]-2-methylphenyl}-5-(pyridin-2-ylmethoxy)pyridine-2-carboxamide; and 
 N-cyclopropyl-4-methyl-3-[(4-{[4-(methylsulfonyl)benzyl]oxy}benzoyl)amino]benzamide; 
 or a pharmaceutically-acceptable salt thereof. 
 
     
     
         10 . A process for preparing a compound of the Formula I, or pharmaceutically-acceptable salt thereof which comprises:—
 (a) reacting a benzoic acid of the Formula II, or a activated derivative thereof, 
 
       
         
           
           
               
               
           
         
         with an amine of the Formula III 
       
       
         
           
           
               
               
           
         
         under standard amide bond forming conditions, wherein Q a , Q b , R 1  and R 2  are as defined in  claim 1  or  claim 2  and wherein any functional group is optionally protected, and:
 (i) removing any protecting groups; and 
 (ii) optionally forming a pharmaceutically-acceptable salt; 
 
         (b) reacting an acid of the Formula IV, or an activated derivative thereof, 
       
       
         
           
           
               
               
           
         
         with an aniline of the Formula VI 
       
       
         
           
           
               
               
           
         
         under standard amide bond forming, wherein Q a , Q b , R 1  and R 2  are as defined in  claim 1  or  claim 2  and wherein any functional group is optionally protected, and:
 (i) removing any protecting groups; 
 (ii) optionally forming a pharmaceutically-acceptable salt; 
 
         (c) for the preparation of a compound of the Formula I wherein a substituent on Q a  or Q b  is (1-6C)alkoxy or substituted (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl]amino or substituted (1-6C)alkylamino, the alkylation of an amide derivative of the Formula I wherein a substituent on Q a  or Q b  is hydroxy or amino. 
       
     
     
         11 . A pharmaceutical composition for use in the treatment of diseases mediated by cytokines which comprises compound of the Formula I as claimed in any one of  claims 1  to  9 , or a pharmaceutically-acceptable salt thereof, in association with a pharmaceutically-acceptable diluent or carrier. 
     
     
         12 . A compound of the Formula I claimed in any one of  claims 1  to  9 , or a pharmaceutically-acceptable salt thereof, for use in a method of treatment of the human or animal body by therapy. 
     
     
         13 . A compound of the Formula I claimed in any one of  claims 1  to  9 , or a pharmaceutically-acceptable salt thereof, in the manufacture of a medicament. 
     
     
         14 . A compound of the Formula I claimed in any one of  claims 1  to  9 , or a pharmaceutically-acceptable salt thereof, in the manufacture of a medicament for use in the treatment of medical conditions mediated by cytokines. 
     
     
         15 . The use of a compound of the Formula I claimed in any one of  claims 1  to  9 , or a pharmaceutically-acceptable thereof, in the manufacture of a medicament for use in the treatment of rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, multiple sclerosis, AIDS, septic shock, congestive heart failure, ischaemic heart disease or psoriasis.