Novel 4-anilinoquinoline-3-carboxamides

Abstract

The present invention relates to novel compounds which are JAK3 Kinase inhibitors, methods for their preparation intermediates and pharmaceutical compositions comprising them.

1 . A compound of formula (I) and pharmaceutically acceptable salts thereof for use in the manufacture of a medicament for the treatment of a disease mediated by JAK3:  
     
       
         
         
             
             
         
       
     
     wherein: 
 n is 0 or 1;  
 X is NR 3  or O;  
 Ar is selected from phenyl, tetrahydronaphthenyl, indolyl, pyrazolyl, dihydroindenyl, 1-oxo-2,3-dihydroindenyl or indazolyl, each of which can be optionally substituted by one or more groups selected from halogen, hydroxy, cyano, C 1 -C 8  alkoxy, CO 2 R 8 , CONR 9 R 0 , C 1 -C 8  alkyl-O—C 1 -C 8  alkyl, C 1 -C 8  alkyl-NR 8 —C 1 -C 8  alkyl, C 1 -C 8  alkyl-CONR 8 —C 1 -C 8  alkyl, C 1 -C 8  alkyl-CONR 9 R 10 , NR 8 COC 1 -C 8  alkyl, C 1 -C 8  thioalkyl, C 1 -C 8  alkyl (itself optionally substituted by one or more hydroxy or cyano groups or fluorine atoms) or C 1 -C 8  alkoxy;  
 R groups are independently hydrogen or C 1 -C 8  alkyl;  
 R 1  and R 2  are independently selected from hydrogen, halogen, nitro, cyano, C 1 -C 8  alkyl, C 1 -C 8  alkoxy, hydroxy, aryl, Y(CR 11   2 ) p NR 4 R 5 , Y(CR 11   2 ) n CONR 4 R 5 , Y(CR 12 ) p CO 2 R 6 , Y(CR 11   2 ) p OR 6 ; Y(CR 11   2 ) p R 6 ;  
 or R 1  and R 2  are linked together as —OCH 2 O— or —OCH 2 CH 2 O—;  
 R 11  groups are independently hydrogen, C 1 -C 8  alkyl, hydroxy or halogen;  
 p is 0, 1, 2, 3, 4 or 5;  
 Y is oxygen, CH 2  or NR 7    
 R 3  is hydrogen or C 1 -C 8  alkyl;  
 R 4  and R 5  each independently represent hydrogen, C 1 -C 8  alkyl or R 4  and R 5  together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated or aromatic heterocyclic ring system optionally containing a further oxygen, sulphur or NR 6  group, or one of R 4  and R 5  is hydrogen or C 1 -C 8  alkyl and the other is a 5- or 6-membered heterocyclic ring system optionally containing a further oxygen, sulphur or nitrogen atom;  
 R 6  is hydrogen, C 1 -C 8  alkyl, phenyl or benzyl;  
 R 7  is hydrogen or C 1 -C 8  alkyl;  
 R 5  is hydrogen or C 1 -C 8  alkyl;  
 R 9  and R 10  are each independently hydrogen or C 1 -C 8  alkyl and pharmaceutically acceptable salts thereof.  
 
   
   
       2 . A compound according to  claim 1  in which both R groups are hydrogen.  
   
   
       3 . A compound according to  claim 1  in which X is NR 3 .  
   
   
       4 . A compound according to any one of  claim 1  in which Ar is phenyl optionally substituted by one or more groups selected from halogen, hydroxy, cyano, C 1 -C 8  alkoxy, CO 2 R 8 , CONR 9 R 10 , C 1 -C 8  alkyl-O—C 1 -C 8  alkyl, C 1 -C 8  alkyl-NR 8 —C 1 -C 8  alkyl, C 1 -C 8  alkyl-CONR 8 —C 1 -C 8  alkyl, C 1 -C 8  alkyl-CONR 9 R 10 , NR 8 COC 1 -C 8  alkyl, C 1 -C 8  thioalkyl, C 1 -C 8  alkyl (itself optionally substituted by one or more hydroxy or cyano groups or fluorine atoms) or C 1 -C 8  alkoxy.  
   
   
       5 . A compound according to any one of  claim 1  in which R 1  is methoxy, ethoxy, OCH 2 CONH 2 , O(CH 2 ) 2 OMe, O(CH 2 ) 2 NR 4 R 5  or O(CH 2 ) 3 NR 4 R 5  where R 4  and R 5  are both hydrogen or methyl or together with the nitrogen to which they are attached form a piperidine or morpholine ring, or R 1  is NH(CH 2 ) 3 NR 4 R 5  where R 4  and R 5  together with the nitrogen to which they are attached form an imidazole ring.  
   
   
       6 . A compound according to any one of  claim 1  in which R 2  is methoxy, ethoxy, O(CH 2 ) 2 OMe, O(CH 2 ) 3 OH, O(CH 2 ) 3 CO 2 Me, O(CH 2 ) 2 NR 4 R 5 , O(CH 2 ) 3 NR 4 R 5  or O(CH 2 ) 4 NR 4 R 5  where one of R 4  or R 5  is methyl and the other is pyridyl, or R 4  and R 5  are selected from hydrogen or methyl or together with the nitrogen to which they are attached form a thiomorpholine, piperidine, morpholine, imidazole, triazole or 2,6-dimethylmorpholine group.  
   
   
       7 . A compound according to  claim 1  which is: 
 6-Benzyloxy-4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    6-Hydroxy-4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(3-Hydroxymethyl-2-methylanilino)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide    4-(3-Hydroxymethyl-2-methylanilino)-7-methoxy-6-(2-methoxyethoxy)-3-quinolinecarboxamide    4-(3-Hydroxymethyl-2-methylanilino)-7-methoxy-6-octyloxy-3-quinolinecarboxamide    4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-6-[2-(4-morpholinyl)ethoxy]-3-quinolinecarboxamide    4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-6-[2-(1-piperidinyl)ethoxy]-3-quinolinecarboxamide    4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-6-[2-(1-pyrrolidinyl)ethoxy]-3-quinolinecarboxamide    6-[2-(dimethylamino)ethoxy]-4-(3-(hydroxymethyl-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    6-[2-(dimethylamino)-2-oxoethoxy]-4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    6-(2-amino-2-oxoethoxy)-4-(3-hydroxymethyl-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide    6-Methoxy-4-[2-(methylsulfanyl)anilino]-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide.    4-[3-(Hydroxymethyl)-2-methylanilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide    4-(1H-Indol-4-ylamino)-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide.    Methyl 4-{[3-(aminocarbonyl)-6-methoxy-4-(2-toluidino)-7-quinolinyl]oxy}butanoate    4-(2-Ethylanilino)-7-(3-hydroxypropoxy)-6-methoxy-3-quinolinecarboxamide    6-Methoxy-7-[2-(4-morpholinyl)ethoxy]-4-(2-toluidino)-3-quinolinecarboxamide.    4-(2-Ethylanilino)-6-methoxy-7-(2-methoxyethoxy)-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-[3-(1H-1,2,4-triazol-1-yl)propoxy]-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-[4-(4-morpholinyl)butoxy]-3-quinolinecarboxamide    7-(3-Chloropropoxy)-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide    7-{3-[(cis)-2,6-Dimethylmorpholinyl]propoxy}-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide    7-{3-[(trans)-2,6-Dimethylmorpholinyl]propoxy}-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide    4-[3-(Hydroxymethyl)-2-methylanilino]-6-methoxy-7-[3-(1-piperidinyl)propoxy]-3-quinolinecarboxamide.    7-{3-[(2-Ethoxyethyl)amino]propoxy}-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide    4-[3-(Hydroxymethyl)-2-methylanilino]-6-methoxy-7-[3-(4-thiomorpholinyl)propoxy]-3-quinolinecarboxamide.    6-[3-(Dimethylamino)propoxy]-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-[3-(1H-imidazol-1-yl)propoxy]-7-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-7-methoxy-6-(3-thienylmethoxy)-3-quinolinecarboxamide    6-[2-(Dimethylamino)ethoxy]-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide    6-(3-Aminopropoxy)-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-7-methoxy-6-[2-(methylamino)ethoxy]-3-quinolinecarboxamide    6-(2-Aminoethoxy)-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide    7-[3-(Dimethylamino)propoxy]-4-(2-ethylanilino)-6-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-{3-[methyl(4-pyridinyl)amino]propoxy}-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-{2-[methyl(4-pyridinyl)amino]ethoxy}-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-[2-(methylamino)ethoxy]-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-7-[2-(1-piperazinyl)ethoxy]-3-quinolinecarboxamide    4-(2-Ethylanilino)-7-[3-(1H-imidazol-1-yl)propoxy]-6-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-7-[2-(1H-imidazol-1-yl)ethoxy]-6-methoxy-3-quinolinecarboxamide    7-(3-Aminopropoxy)-4-(2-ethylanilino)-6-methoxy-3-quinolinecarboxamide    7-Hydroxy-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide    6-{[3-(1H-imidazol-1-yl)propyl]amino}-7-methoxy-4-(2-toluidino)-3-quinolinecarboxamide    7-Methoxy-6-[(2-methoxyethyl)amino]-4-(2-toluidino)-3-quinolinecarboxamide    7-Methoxy-6-{[2-(4-morpholinyl)ethyl]amino}-4-(2-toluidino)-3-quinolinecarboxamide    7-Methoxy-6-{[3-(4-morpholinyl)propyl]amino}-4-(2-toluidino)-3-quinolinecarboxamide    6-Methoxy-7-{[2-(4-morpholinyl)ethyl]aminol}-4-(2-toluidino)-3-quinolinecarboxamide    6-Methoxy-7-[(2-methoxyethyl)amino]-4-(2-toluidino)-3-quinolinecarboxamide    7-{[3-(1H-imidazol-1-yl)propyl]amino}-6-methoxy-4-(2-toluidino)-3-quinolinecarboxamide    7-[(1-Benzyl-4-piperidinyl)amino]-6-methoxy-4-(2-toluidino)-3-quinolinecarboxamide    6-Methoxy-6-{[3-(4-morpholinyl)propyl]amino}-4-(2-toluidino)-3-quinolinecarboxamide    4-[3-(Hydroxymethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Bromoanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-(4-Hydroxy-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    6,7-Dimethoxy-4-(2-methoxyanilino)-3-quinolinecarboxamide    4-(4-Fluoro-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-[(1-Ethyl-1H-pyrazol-5-yl)amino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Aminocarbonyl-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy 4-(2,3-dimethylanilino)-3-quinolinecarboxamide    6,7-Dimethoxy-4-(5,6,7,8-tetrahydro-1-naphtalenylamino)-3-quinolinecarboxamide    4-(4-Carboxy-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(1H-Indol-4-ylamino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Chloro-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[2-(Aminocarbonyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Hydroxy-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(3-methoxy-2-methylanilino)-3-quinolinecarboxamide    6,7-Dimethoxy-4-[(1-methyl-1H-indol-4-yl)amino]-3-quinolinecarboxamide    6,7-Dimethoxy-4-[(1-oxo-2,3-dihydro-1H-inden-4-yl)amino]-3-quinolinecarboxamide    4-[1-Hydroxy-2,3-dihydro-1H-inden-4-yl)amino-6,7-dimethoxy-3-quinolinecarboxamide    4-(4-Carboxy-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(4-methoxycarbonyl-2-methylanilino)-3-quinolinecarboxamide    4-(4-Hydroxymethyl-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(2-propylanilino)-3-quinolinecarboxamide    4-(2-Isopropylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[2-(sec-Butyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-[3-(methoxymethyl)-2-methylanilino]-3-quinolinecarboxamide    4-[3-(iso-Butoxymethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-[3-(cyanomethyl)-2-methylanilino]-6,7-dimethoxy-3-quinoline carboxamide    4-{3-[(Ethylamino)methyl]-2-methylanilino}-6,7-dimethoxy-3-quinolinecarboxamide    4-{3-[2-(Ethylamino)-2-oxoethyl]-2-methylanilino}-6,7-dimethoxy-3-quinolinecarboxamide    Ethyl 2-(3-{[3-(aminocarbonyl)-6,7-dimethoxy-4-quinolinyl]amino}-2-methylphenyl)acetate    4-[3-(2-Amino-2-oxoethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-[3-(2-Hydroxyethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-{2-[(2-Hydroxyethyl)amino]-2-oxoethyl}-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    tert-Butyl 3-{[3-(aminocarbonyl)-6,7-dimethoxy-4-quinolinyl]amino}-2-methylbenzylcarbamate    4-[3-(Aminomethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(4-Fluoro-2-methylanilino)-6-methoxy-3-quinolinecarboxamide    4-(4-Bromo-2-methylanilino)-6-methoxy-3-quinolinecarboxamide    4-(4-Chloro-2-methylanilino)-6-methoxy-3-quinolinecarboxamide    4-(2,4-Dimethylanilino)-6-methoxy-3-quinolinecarboxamide    6-Methoxy-4-(4-methoxy-2-methylanilino)-3-quinolinecarboxamide    4-(4-Hydroxy-2-methylanilino)-6-methoxy-3-quinolinecarboxamide    4-(2-Bromoanilino)-6-methoxy-3-quinolinecarboxamide    4-(2,4-Dimethoxyanilino)-6-methoxy-3-quinolinecarboxamide    6-Methoxy-4-(2-methoxyanilino)-3-quinolinecarboxamide    4-(2-Ethoxyanilino)-6-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-6-methoxy-3-quinolinecarbox amide    6-Methoxy-4-(2-toluidino)-3-quinolinecarboxamide    6-Methoxy-4-[2-(methylsulfanyl)anilino]-3-quinolinecarboxamide    4-(4-Bromo-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(4-Chloro-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,4-Dimethylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(4-methoxy-2-methylanilino)-3-quinolinecarboxamide    4-(2-Bromo-4-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Bromo-4-fluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,4-Dimethoxyanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(4-Fluoro-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(4-Bromo-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(4-Chloro-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(2,4-Dimethylanilino)-7-methoxy-3-quinolinecarboxamide    7-Methoxy-4-(4-methoxy-2-methylanilino)-3-quinolinecarboxamide    4-(4-Hydroxy-2-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(2-Bromoanilino)-7-methoxy-3-quinolinecarboxamide    4-(2-Bromo-4-methylanilino)-7-methoxy-3-quinolinecarboxamide    4-(2-Bromo-4-fluoroanilino)-7-methoxy-3-quinolinecarboxamide    4-(2,4-Dimethoxyanilino)-7-methoxy-3-quinolinecarboxamide    6,7-Dichloro-4-(4-methoxy-2-methylanilino)-3-quinolinecarboxamide    6,7-Dichloro-4-(2,4-dimethoxyanilino)-3-quinolinecarboxamide    4-(2-Ethylanilino)-3-quinolinecarboxamide    4-(2-Toluidino)-3-quinolinecarboxamide    4-[2-(Methylsulfanyl)anilino]-3-quinolinecarboxamide    4-(2-Ethoxyanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[2-(Hydroxymethyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(2-toluidino)-3-quinolinecarboxamide    6,7-Dimethoxy-4-[2-(methylsulfanyl)anilino]-3-quinolinecarboxamide    4-(2,4-Dibromoanilino)-6,7-dimethoxy-3-quinolinecarboxamide    7-Methoxy-4-(2-methoxyanilino)-3-quinolinecarboxamide    4-(2-Ethoxyanilino)-7-methoxy-3-quinolinecarboxamide    4-[2-(Aminocarbonyl)anilino]-7-methoxy-3-quinolinecarboxamide    4-(2-Ethylanilino)-7-methoxy-3-quinolinecarboxamide    7-Methoxy-4-(2-toluidino)-3-quinolinecarboxamide    7-Methoxy-4-[2-(methylsulfanyl)anilino]-3-quinolinecarboxamide    6,7-Dichloro-4-(2-methoxyanilino)-3-quinolinecarboxamide    6,7-Dichloro-4-(2-ethylanilino)-3-quinolinecarboxamide    6,7-Dichloro-4-[2-(methylsulfanyl)anilino]-3-quinolinecarboxamide    4-(2,5-Dimethylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-(5-Fluoro-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(5-Chloro-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-(3-Fluoro-2-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-(4-Hydroxy-2,5-dimethylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-(2-Hydroxy-4-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide.    4-Anilino-6,7-dimethoxy-3-quinolinecarboxamide    4-(4-Chloro-2-fluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Fluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,6-Difluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Bromoanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Fluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(4-methoxyanilino)-3-quinolinecarboxamide    4-(3-Chloroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Chloroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[3-(Acetylamino)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,5-Difluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(1H-Indol-5-ylamino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(1H-Indazol-5-ylamino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(1H-Indazol-6-ylamino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,4-Difluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Fluoro-4-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,4-Dichloroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,5-Dichloroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[2-(2-Hydroxyethyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Chloro-4-fluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-[3-(methylsulfanyl)anilino]-3-quinolinecarboxamide    6,7-Dimethoxy-4-(2-methoxy-5-methylanilino)-3-quinolinecarboxamide    4-[4-(Dimethylamino)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-[4-(methylsulfanyl)anilino]-3-quinolinecarboxamide    4-[4-(2-Hydroxyethyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(3-Hydroxy-4-methoxyanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2,3-Dichloroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    6,7-Dimethoxy-4-(2,3,4-trifluoroanilino)-3-quinolinecarboxamide    6,7-Dimethoxy-4-(3-toluidino)-3-quinolinecarboxamide    4-(2-Hydroxy-4-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Fluoro-4-hydroxyanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[2-(Hydroxymethyl)-4-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Chloro-4-fluoroanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-(2-Fluoro-5-methylanilino)-6,7-dimethoxy-3-quinolinecarboxamide    4-[(2-Cyanophenyl)amino]-6,7-dimethoxyquinoline-3-carboxamide    4-[(2,5-Difluorophenyl)amino]-6,7-dimethoxyquinoline-3-carboxamide    4-(1H-Indol-5-ylamino)-6,7-dimethoxyquinoline-3-carboxamide    6,7-Dichloro-4-(2-methylanilino)-3-quinolinecarboxamide.    4-(2,3-Dihydro-1H-inden-1-ylamino)-6,7-dimethoxy-3-quinoline carboxamide    6,7-Dimethoxy-4-{[2-(trifluoromethyl)benzyl]amino}-3-quinoline carboxamide    6,7-Dimethoxy-4-[(1-phenylethyl)amino]-3-quinolinecarboxamide    4-(3-Hydroxymethyl-2-methylanilino)-3-quinolinecarboxamide    9-(3-Hydroxymethyl-2-methylanilino)-2,3-dihydro[1,4]dioxino[2,3 g]quinoline-8-carboxamide    4-[(2-ethylphenyl)amino]-7-methoxy-6-[2-(propylamino)ethoxy]quinoline-3-carboxamide,    6-[2-(ethylamino)ethoxy]-4-[(2-ethylphenyl)amino]-7-methoxyquinoline-3-carboxamide,    6-[2-(isopropylamino)ethoxy]-7-methoxy-4-[(3-methoxy-2-methylphenyl)amino]quinoline-3-carboxamide,    6-[2-(dimethylamino)ethoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-7-methoxyquinoline-3-carboxamide,    6-[3-(diethylamino)propoxy]-4-{[3-(hydroxymethyl)-2-methylphenyl]amino}-7-methoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-7-methoxy-6-[2-(methylamino)ethoxy]quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-(pyridin-4-ylamino)propoxy]quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-[(2-amino-2-oxoethyl)amino]propoxy]-quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-(1H-pyrazol-3-ylamino)propoxy]quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-(pyridin-2-ylamino)propoxy]quinoline-3-carboxamide,    Ethyl 4-[(3-(aminocarbonyl)-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinolin-7-yl)oxy]butanoate,    7-[3-(diethylamino)propoxy]-6-methoxy-4-[(2-methoxyphenyl)amino]quinoline-3-carboxamide,    7-[3-(ethylamino)propoxy]-6-methoxy-4-{[2-(trifluoromethyl)phenyl]amino}quinoline-3-carboxamide,    7-[3-(ethylamino)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-[3-(isopropylamino)propoxy]-6-methoxyquinoline-3-carboxamide,    7-[3-(ethylamino)propoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-[3-(propylamino)propoxy]quinoline-3-carboxamide,    7-[3-(dimethylamino)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-3-carboxamide,    7-[3-(diethylamino)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carboxamide,    7-[3-(dimethylamino)propoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinoline-3-carboxamide,    7-[3-(diethylamino)propoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinoline-3-carboxamide,    7-{3-[(2-ethoxyethyl)amino]propoxy}-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-thiomorpholin-4-ylpropoxy)quinoline-3-carboxamide,    4-{[3-(hydroxymethyl)-2-methylphenyl]amino}-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-3-carboxamide,    7-[3-(1,1-dioxidothiomorpholin-4-yl)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carboxamiide,    4-{[3-(hydroxymethyl)-2-methylphenyl]amino}-7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-[3-(1H-1,2,4-triazol-1-yl)propoxy]quinoline-3-carboxamide,    7-(3-azepan-1-ylpropoxy)-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    6,7-dimethoxy-4-{[2-(methylthio)phenyl]amino}quinoline-3-carboxamide trifluoroacetate,    6,7-dimethoxy-4-[(4-methoxy-2-methylphenyl)amino]quinoline-3-carboxamide,    4-{[2-bromo-3-(hydroxymethyl)phenyl]amino}-6,7-dimethoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6,7-dimethoxyquinoline-3-carboxamide,    or a pharmaceutically acceptable salt thereof.    
   
   
       8 . A compound of formula (IA):  
     
       
         
         
             
             
         
       
     
     in which 
 Ar is phenyl substituted by ethyl, propyl, hydroxymethyl or CO 2 H or disubstituted by methyl and hydroxymethyl;  
 R 1  is methoxy, ethoxy or a group OCH 2 CONH 2 , OCH 2 CH 2 OCH 3 , or O(CH 2 ) p NR 4 R 5  where p is 2 or 3 and R 4  and R are hydrogen, methyl, ethyl or propyl or together R 1  and R 5  form a pyrrolidine, imidazole or morpholine ring;  
 R 2  is methoxy, ethoxy or O(CH 2 ) p NR 4 R 5  where p is 2, 3 or 4 and R 4  and R 5  are hydrogen, methyl or ethyl or one of R 4  or R 5  is methyl and the other is pyridyl or pyrazole or R 4  and R 5  form a piperidine, hydroxypiperidine, thiomorpholine, morpholine, pyrrolidine, 2,6-dimethylmorpholine imidazole or triazole ring,  
 or a pharmaceutically acceptable salt or solvate thereof,  
 provided that when A is phenyl substituted by ethyl or propyl or disubstituted by methyl, then R 1  and R 2  are not both methoxy, R 1  and R 2  are not both ethoxy or one of R 1 /R 2  is not methoxy when the other is ethoxy.  
 
   
   
       9 . A compound of formula (IA) selected from: 
 4-(2-ethylanilino)-6-methoxy-7-{2-[methyl(4-pyridinyl)amino]ethoxy}-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-7-[3-(4-thiomorpholinyl)propoxy]-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-7-[3-(1-piperidinyl)propoxy]-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide,    7-[3-(dimethylamino)propoxy]-4-(2-ethylanilino)-6-methoxy-3-quinolinecarboxamide,    7-[3-(dimethylamino)propoxy]-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide,    7-{3-[(2R,6S)-2,6-dimethylmorpholinyl]propoxy}-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-methoxy-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-methoxy-7-[4-(4-morpholinyl)butoxy]-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-methoxy-7-{3-[methyl(4-pyridinyl)amino]propoxy}-3-quinolinecarboxamide,    4-(2-ethylanilino)-7-methoxy-6-[2-(methylamino)ethoxy]-3-quinolinecarboxamide,    7-{3-[(2S,6S)-2,6-dimethylmorpholinyl]propoxy}-4-[3-(hydroxymethyl)-2-methylanilino]-6-methoxy-3-quinolinecarboxamide,    4-(2-ethylanilino)-7-[3-(1H-imidazol-1-yl)propoxy]-6-methoxy-3-quinolinecarboxamide,    6-(2-aminoethoxy)-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide,    6-methoxy-4-[2-(methylsulfanyl)anilino]-7-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide,    6-methoxy-7-[3-(4-morpholinyl)propoxy]-4-(2-toluidino)-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-methoxy-7-[3-(1H-1,2,4-triazol-1-yl)propoxy]-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-methoxy-7-[2-(methylamino)ethoxy]-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-methoxy-7-(2-methoxyethoxy)-3-quinolinecarboxamide,    4-(2-ethylanilino)-7-(3-hydroxypropoxy)-6-methoxy-3-quinolinecarboxamide,    6-methoxy-7-[2-(4-morpholinyl)ethoxy]-4-(2-toluidino)-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxy-6-[2-(1-pyrrolidinyl)ethoxy]-3-quinolinecarboxamide    3-{[3-(aminocarbonyl)-6,7-dimethoxy-4-quinolinyl]amino}-2-methylbenzoic acid,    4-[3-(hydroxymethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide,    4-(2-ethylanilino)-7-[2-(1H-imidazol-1-yl)ethoxy]-6-methoxy-3-quinolinecarboxamide,    4-[3-(2-hydroxyethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide,    7-methoxy-6-{[2-(4-morpholinyl)ethyl]amino}-4-(2-to luidino)-3-quinolinecarboxamide,    4-(2-ethylanilino)-6-[3-(1H-imidazol-1-yl)propoxy]-7-methoxy-3-quinolinecarboxamide,    4-(2-ethylanilino)-7-methoxy-6-[2-(1-pyrrolidinyl)ethoxy]-3-quinolinecarboxamide,    7-(3-aminopropoxy)-4-(2-ethylanilino)-6-methoxy-3-quinolinecarboxamide,    methyl 4-{[3-(aminocarbonyl)-6-methoxy-4-(2-toluidino)-7-quinolinyl]oxy}butanoate,    4-[3-(aminomethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide,    6-{[3-(1H-imidazol-1-yl)propyl]amino}-7-methoxy-4-(2-toluidino)-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxy-6-(2-methoxyethoxy)-3-quinolinecarboxamide,    6-[2-(dimethylamino)ethoxy]-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide,    4-[3-(cyanomethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide,    4-[3-(2-amino-2-oxoethyl)-2-methylanilino]-6,7-dimethoxy-3-quinolinecarboxamide,    6-(3-aminopropoxy)-4-(2-ethylanilino)-7-methoxy-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxy-6-[3-(4-morpholinyl)propoxy]-3-quinolinecarboxamide,    4-[3-(hydroxymethyl)-2-methylanilino]-7-methoxy-6-[2-(4-morpholinyl)ethoxy]-3-quinolinecarboxamide,    and pharmaceutically acceptable salts thereof.    
   
   
       10 . A compound of formula (IA) selected from: 
 4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-(pyridin-4-ylamino)propoxy]quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-[(2-amino-2-oxoethyl)amino]propoxy]-quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-(1H-pyrazol-3-ylamino)propoxy]quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-7-methoxy-6-[3-(pyridin-2-ylamino)propoxy]quinoline-3-carboxamide,    Ethyl 4-[(3-(aminocarbonyl)-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinolin-7-yl)oxy]butanoate,    7-[3-(diethylamino)propoxy]-6-methoxy-4-[(2-methoxyphenyl)amino]quinoline-3-carboxamide,    7-[3-(ethylamino)propoxy]-6-methoxy-4-{[2-(trifluoromethyl)phenyl]amino}quinoline-3-carboxamide,    7-[3-(ethylamino)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxanide,    4-[(2-ethylphenyl)amino]-7-[3-(isopropylamino)propoxy]-6-methoxyquinoline-3-carboxamide,    7-[3-(ethylamino)propoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-[3-(propylamino)propoxy]quinoline-3-carboxamide,    7-[3-(dimethylamino)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-3-carboxamide,    7-[3-(diethylamino)propoxy]-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carboxamide,    7-[3-(dimethylamino)propoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinoline-3-carboxamide,    7-[3-(diethylamino)propoxy]-4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxyquinoline-3-carboxamide,    7-{3-[(2-ethoxyethyl)amino]propoxy}-4-[(2-ethylphenyl)amino]-6-methoxyquinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carboxamide,    4-[(2-ethylphenyl)amino]-6-methoxy-7-(3-thiomorpholin-4-ylpropoxy)quinoline-3-carboxamide,    4-{[3-(hydroxymethyl)-2-methylphenyl]amino}-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carboxamide,    4-{[3-(hydroxymethyl)-2-methylphenyl]amino}-7-[3-(3-hydroxypiperidin-1-yl)propoxy]-6-methoxyquinoline-3-carboxamide,    4-{[2-ethyl-3-(hydroxymethyl)phenyl]amino}-6-methoxy-7-[3-(1H-1,2,4-triazol-1-yl)propoxy]quinoline-3-carboxamide,    and pharmaceutically acceptable salts thereof.    
   
   
       11 . A pharmaceutical composition comprising a compound of formula (IA) or a pharmaceutically acceptable salt thereof in association with a pharmaceutically acceptable carrier.  
   
   
       12 . A method of treating a disease or condition mediate by JAK3 which comprises administering to a patient in need of such treatment a compound of formula (I) as defined in  claim 1  or a pharmaceuticaly acceptable salt thereof.  
   
   
       13 . A method according to  claim 14  in which the disease or condition is asthma, host versus graft rejection/transplantation or rheumatoid arthritis.  
   
   
       14 . A process for the preparation of a compound of formula (I) which comprises: 
 (a) reaction of a compound of formula (II):                          in which R 1  and R 2  are as defined in formula (1) or are protected derivatives thereof and R 20  is a leaving group, with a compound of formula (D):      Ar(CR 2 ) 2 —NH 2   (III)    in which Ar and R are as defined in formula (l) or are protected derivatives thereof, or    (b) for compounds of formula (I) where R 1  and/or R 2  are groups Y(CH 2 ) p NR 4 R 5 , Y(CH 2 ) p CONR 4 R 5 , Y(CH 2 ) p CO 2 R 6 , Y(CH 2 ) p OR 6  or Y(CH 2 ) p R 6  where Y is oxygen, reaction of a compound of formula (IV):                          where the R 1′  or R 2′  to be converted into a group Y(CH 2 ) p NR 4 R 5 , Y(CH 2 ) p CONR 4 R 5 , Y(CH 2 ) p CO 2 R 6 , Y(CH 2 ) p OR 6  or Y(CH 2 ) p R 6  is hydroxy and the other R 1′  or R 2′  together with Ar are as defined above for process (a) with a compound of formula (V):      L—(CH 2 ) p R 21   (V)    where R 21  is NR 4 R 5 , CONR 4 R 5 , CO 2 R 6 , OR 6  or R 6  and R 4 , R 5  and R 6  are as defined in formula (I) or are protected derivatives thereof, and optionally thereafter process (a) or (b)    removing any protecting groups    converting a compound of formula (1) into a further compound of formula (1)    forming a pharmaceutically acceptable salt.    
   
   
       15 . A method of treating asthma comprising administering to a patient in need of such treatment a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt thereof.  
   
   
       16 . A method of treating host versus graft rejection/transplantation comprising administering to a patient in need of such treatment a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt thereof.  
   
   
       17 . A method of treating rheumatoid arthritis comprising administering to a patient in need of such treatment a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt thereof.  
   
   
       18 . The method of  claim 15 , wherein the compound of formula (1) is according to  claim 7 .  
   
   
       19 . The method of  claim 15 , wherein the compound of formula (1) is according to  claim 11   
   
   
       20 . The compound of  claim 1 , wherein X is NR′; 
 Ar is phenyl optionally substituted by one or more groups selected from halogen, hydroxy, cyano, C 1 -C 8 alkoxy, CO 2 R 8 , CONR 9 R 10 , C 1 -Csalkyl-O—C 1 -C 8 alkyl, C 1 -C 8 alkyl-NR 8 —C 1 -C 8 alkyl, C 1 -C 8 alkyl-CONR 8 -C 1 -C 8 alkyl, C 1 -C 8 alkyl-CONR 9 R 10 , NR 8 C 1 -C 8 alkyl, C 1 -C 8 thioalkyl, C 1 -C 8 alkyl (itself optionally substituted by one or more hydroxy or cyan groups or fluorine atoms) or C 1 -C 8 alkoxy;    R1 is methoxy, ethoxy, OCH2CONH2, O(CH2)2OMe, O(CH2)2NR 4 R 5  or O(CH2)3NR 4 R 5  where R 4  and R 5  are both hydrogen or methyl or together with the nitrogen to which they are attached form a piperidine or morpholine ring, or R 1  is NH(CH 2 ) 3 NR 4 R 5  where R 4  and R 5  together with the nitrogen to which they are attached form an imidazole ring; and R 2  is methoxy, ethoxy, O(CH 2 ) 2 OMe, O(CH 2 ) 3 OH, O(CH 2 ) 3 CO 2 Me, O(CH 2 ) 2 NR 4 R 5 , O(CH 2 ) 3 NR 4 R 5  or O(CH 2 ) 4 NR 4 R 5  where one of R 4  or R 5  is methyl and the other is pyridyl, or R4 and R5 are selected from hydrogen or methyl or together with the nitrogen to which they are attached form a thiomorpholine, piperidine, morpholine, imidazole, triazole or 2,6-dimethylmorpholine group.