5-Arylsulfonyl-imidazo[1',2':1,6]pyrido[2,3-b]pyrazine-6-amines and related compounds

Abstract

A compound of the formula wherein a, X, R 1 , R 2 , R 3 and R 4 are as defined above, useful in the treatment of respiratory, allergic, rheumatoid, body weight regulation, inflammatory and central nervous system disorders such as asthma, chronic obstructive pulmonary disease, adult respiratory diseases syndrome, shock, fibrosis, pulmonary hypersensitivity, allergic rhinitis, atopic dermatitis, psoriasis, weight control, rheumatoid arthritis, cachexia, crohn's disease, ulcerative colitis, arthritic conditions and other inflammatory diseases, depression, multi-infarct dementia and AIDS.

1 . A compound of the formula  
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof; wherein 
 a is 1, 2, 3 or 4;  
 X is CH or N;  
 R 1  and R 2  are each independently selected from hydrogen, (C 1 -C 6 )alkyl, cyano, amino, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 3 -C 7 )cycloalkyl, (C 6 -C 10 )aryl and a saturated or unsaturated, cyclic or bicyclic (C 2 -C 9 )heterocyclic group containing as the heteroatom one to four of the group consisting of oxygen, sulfur, nitrogen or NR 6  wherein R 6  is hydrogen or (C 1 -C 6 )alkyl;  
 R 3  and R 4  are each independently selected from hydrogen, halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, cyano, hydroxy, amino, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkoxy, (C 6 -C 10 )aryl or a saturated or unsaturated, cyclic or bicyclic (C 2 -C 9 )heterocyclic group containing as the heteroatom one to four of the group consisting of oxygen, sulfur, nitrogen or NR 6  wherein R 6  is defined as above;  
 or R 1  and R 2  may be taken together with the carbons to which they are attached to form a compound of formula II  
                     
  wherein a, X, R 3  and R 4  are as defined above;  
 b is 1, 2, 3 or 4; and  
 R 5  is hydrogen, halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, cyano, hydroxy, amino, (C 1 -C 6 )alkylamino, ((C 1 -C 6 )alkyl) 2 amino, (C 3 -C 7 )cycloalkyl, (C 3 -C 7 )cycloalkoxy, (C 6 -C 10 )aryl or a saturated or unsaturated, cyclic or bicyclic (C 2 -C 9 )heterocyclic group containing as the heteroatom one to four of the group consisting of oxygen, sulfur, nitrogen or NR 6  wherein R 6  is defined as above.  
 
     
     
         2 . A compound according to  claim 1 , wherein X is nitrogen.  
     
     
         3 . A compound according to  claim 1 , wherein R 1  is hydrogen, (C 1 -C 6 )alkyl, amino, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         4 . A compound according to  claim 1 , wherein R 2  is hydrogen, (C 1 -C 6 )alkyl, amino, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         5 . A compound according to  claim 1 , wherein R 3  is hydrogen, halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, cyano, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         6 . A compound according to  claim 1 , wherein R 4  is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         7 . A compound according to  claim 1 , wherein R 5  is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 8 )alkoxy, cyano, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         8 . A compound according to  claim 1 , wherein X is nitrogen; R 1  is hydrogen, (C 1 -C 6 )alkyl, amino, cycloalkyl or (C 6 -C 10 )aryl; R 2  is hydrogen, (C 1 -C 6 )alkyl, amino, cycloalkyl or (C 6 -C 10 )aryl; R 3  is hydrogen, halo, (C 1 -C 6 )alkyl, cyano, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl; and R 4  is hydrogen, (C 1 -C 6 )alkyl, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         9 . A compound according to  claim 1 , wherein X is nitrogen; R 3  is hydrogen, halo, (C 1 -C 6 )alkyl, cyano, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl; R 4  is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl and R 5  is hydrogen, (C 1 -C 6 )alkyl, cyano, amino, hydroxy, cycloalkyl or (C 6 -C 10 )aryl.  
     
     
         10 . A compound according to  claim 1 , wherein said compound is selected from the group consisting of: 
 5-[(4-methylphenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-methylphenyl)sulfonyl]-[1,2,4]triazolo[4′,3′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-ethylphenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-isopropylphenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-propylphenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-methoxyphenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-ethylphenyl)sulfonyl]-[1,2,4]triazolo[4′,3′:1,6]pyrido[2,3-b]quinoxaline-4-amine;    5-[(4-fluorophenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-chlorophenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(3-methoxyphenyl)sulfonyl]-imidazo[1′,2′:1,6]pyrido[2,3-b]pyrazin-6-amine;    5-[(4-methoxyphenyl)sulfonyl]-[1,2,4]triazolo[4′,3′:1,6]pyrido[2,3-b]pyrazin-6-amine; and    5-[(4-methoxyphenyl)sulfonyl]-[1,2,4]triazolo[4′,3′:1,6]pyrido[2,3-b]quinoxaline-4-amine.    
     
     
         11 . A pharmaceutical composition for the treatment of respiratory, allergic, rheumatoid, body weight regulation, inflammatory and central nervous system disorders such as asthma, chronic obstructive pulmonary disease, adult respiratory diseases syndrome, shock, fibrosis, pulmonary hypersensitivity, allergic rhinitis, atopic dermatitis, psoriasis, weight control, rheumatoid arthritis, cachexia, Crohn's disease, ulcerative colitis, arthritic conditions and other inflammatory diseases, depression, multi-infarct dementia and AIDS in a mammal, including a human, comprising an amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof, effective in such preventions or treatment and a pharmaceutically acceptable carrier.  
     
     
         12 . A method for the treatment of respiratory, allergic, rheumatoid, body weight regulation, inflammatory and central nervous system disorders such as asthma, chronic obstructive pulmonary disease, adult respiratory diseases syndrome, shock, fibrosis, pulmonary hypersensitivity, allergic rhinitis, atopic dermatitis, psoriasis, weight control, rheumatoid arthritis, cachexia, Crohn's disease, ulcerative colitis, arthritic conditions and other inflammatory diseases, depression, multi-infarct dementia and AIDS in a mammal, including a human, comprising administering to said mammal an amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof, effective in such treatment.