Quinoline Derivatives as CRTH2 Antagonists

Abstract

The invention relates to compounds of formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as defined in the description, their use as medicament, pharmaceutical compositions containing them and processes for their preparation.

1 - 33 . (canceled)  
   
   
       34 . A method for treating a disorder in a mammal for which CRTH2 antagonism is relevant comprising administering to said mammal in need of such treatment a compound of formula (I):  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is H, (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, (C 2 -C 4 )alkynyl or (CH 2 ) m —R 1 , in which R′ 1  is selected from aromatic heterocycle, phenyl and (C 3 -C 6 )cycloalkyl wherein the phenyl, the heterocycle and the cycloalkyl groups are unsubstituted or substituted by one to three groups independently selected from 
 Q 1 , and  
 (C 1 -C 4 )alkyl optionally substituted with one to three groups which are the same or different and which are selected from Q 1 ,  
 wherein Q 1  is selected from halogen, NO 2 , CN, SO 2 CH 3 , SO 2 NR 9 R 10 , OR 9 , COOR 9 , C(═O)NR 9 R 10 , NR 9 R 10 , NR 9 SO 2 R 10 , NR 9 C(═O)R 10  and C(═O)R 9  wherein R 9  and R 10  are the same or different and are selected from H and (C 1 -C 4 )alkyl;  
 
 m is an integer selected from 0, 1 and 2;  
 R 2  is (C 1 -C 4 )alkyl, wherein the alkyl group is substituted with one to three substituents independently selected from halogen, OR 9 , NR 9 R 10 , COOR 9 , C(═O)NR 9 R 10 , NHSO 2 R 9  and C(═O)(C 1 -C 4 )alkyl;  
 R 3  is (C 3 -C 6 )cycloalkyl or -A-R 3 , wherein 
 A is a bond, (C 1 -C 3 )alkylene or (C 2 -C 3 )alkenylene;  
 R′ 3  is (C 6 -C 12 )aryl or a 5- to 10-membered heterocycle, optionally aromatic, wherein the aryl and the heterocycle groups are unsubstituted or substituted by one to three substituents independently selected from  
 (C 6 -C 12 )aryl,  
 an aromatic heterocyle,  
 Q 2 , and  
 (C 1 -C 4 )alkyl optionally substituted with one to three groups which are the same or different and which are selected from Q 2 ,  
 wherein Q 2  is selected from halogen, NO 2  CN, SO 2 CH 3 , SO 2 NR 9 R 10 , OR 9 , SR 9 , OCH 2 CF 3 , COOR 9 , C(═O)NR 9 R 10 , NR 9 R 10 , NR 9 SO 2 R 10 , NR 9 C(═O)R 10  and C(═O)R 9 ;  
 
 R 4  is H or (C 1 -C 4 )-alkyl;  
 R 5 , R 6 , R 7  and R 8  are the same or different and are selected from 
 H, Q 3 , and  
 (C 1 -C 4 )alkyl optionally substituted with one to three groups which are the same or different and which are selected from Q 3 ,  
 wherein Q 3  is selected from halogen, NO 2 , CN, SO 2 CH 3 , SO 2 NR 9 R 10 , OR 9 , SR 9 COOR 9 , C(═O)NR 9 R 10 , NR 9 R 10 , NR 9 SO 2 R 10 , NR 9 C(═O)R 10  and C(═O)R 9 ;  
 an optical isomer thereof, an N-oxide thereof or a pharmaceutically acceptable salt of said compound, optical isomer or N-oxide.  
 
 
   
   
       35 . A method of  claim 34  wherein said disorder is selected from rheumatoid arthritis, osteoarthritis, atherosclerosis, Crohn's disease, colitis ulcerosa, inflammatory bowel disease; disorders of the skin, psoriasis, eczema, erythema, pruritis, acne, systemic lupus erythematous, chronic obstructive pulmonary disease, angioedema, stroke, diseases marked by reperfusion injury, graft rejection, autoimmune diseases, allergic diseases, allergic asthma, atopic dermatitis, and allergic rhinitis.  
   
   
       36 . A method of  claim 35  wherein said disorder is selected from asthma and allergic rhinitis.