Amide substituted imidazoquinolines

Abstract

Imidazoquinoline and tetrahydroimidazoquinoline compounds that contain amide functionality at the 1-position are useful as immune response modifiers. The compounds and compositions of the invention can induce the biosynthesis of various cytokines and are useful in the treatment of a variety of conditions including viral diseases and neoplastic diseases.

1 .- 23 . (canceled) 
     
     
         24 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula (Ib): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is —C 2-4  alkyl-NR 3 —CO—R 4  wherein R 4  is heterocyclyl which may be unsubstituted or substituted by one or more substituents selected from the group consisting of:
 -alkyl; 
 -alkenyl; 
 -alkynyl, 
 -(alkyl) 0-1 -aryl; 
 -(alkyl) 0-1 -(substituted aryl); 
 -(alkyl) 0-1 -heterocyclyl; 
 -(alkyl) 0-1 -(substituted heterocycyl); 
 -(alkyl) 0-1 -heteroaryl; 
 -(alkyl) 0-1 -(substituted heteroaryl); 
 —O-alkyl; 
 —O-(alkyl) 0-1 -aryl; 
 —O-(alkyl) 0-1 -(substituted aryl); 
 —O-(alkyl) 0-1 -heterocyclyl; 
 —O-(alkyl) 0-1 -(substituted heterocyclyl); 
 —O-(alkyl) 0-1 -heteroaryl; 
 —O-(alkyl) 0-1 -(substituted heteroaryl); 
 —CO-aryl; 
 —CO-(substituted aryl); 
 —CO-heteroaryl; 
 —CO-(substituted heteroaryl); 
 —COOH; 
 —CO—O-alkyl; 
 —CO-alkyl; 
 —S(O) 0-2 -alkyl; 
 —S(O) 0-2 -(alkyl) 0-1 -aryl; 
 —S(O) 0-2 -(alkyl) 0-1 -(substituted aryl); 
 —S(O) 0-2 -(alkyl) 0-1 -heterocyclyl; 
 —S(O) 0-2 -(alkyl) 0-1 -(substituted heterocyclyl); 
 —S(O) 0-2 -(alkyl) 0-1 -heteroaryl; 
 —S(O) 0-2 -(alkyl) 0-1 -(substituted heteroaryl); 
 —P(O)(OR 3 ) 2 ; 
 —NR 3 —CO—O-alkyl; 
 —N 3 ; 
 -halogen; 
 —NO 2 ; 
 —CN; 
 -haloalkyl; 
 —O-haloalkyl; 
 —CO-haloalkyl; 
 —OH; 
 —SH; 
 or R 4  is 
 
 
       
         
           
           
               
               
           
         
         wherein R 5  is an aryl, (substituted aryl), heteroaryl, (substituted heteroaryl), heterocyclyl or (substituted heterocyclyl) group; 
         R 2  is selected from the group consisting of:
 -hydrogen; 
 -alkyl; 
 -alkenyl; 
 -aryl; 
 -(substituted aryl); 
 -heteroaryl; 
 -(substituted heteroaryl); 
 -heterocyclyl; 
 -(substituted heterocyclyl); 
 -alkyl-O-alkyl; 
 -alkyl-O-alkenyl; and 
 -alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
 —OH; 
 -halogen; 
 —N(R 3 ) 2 ; 
 —CO—N(R 3 ) 2 ; 
 —CO—C 1-10 alkyl; 
 —CO—O—C 1-10 alkyl; 
 —N 3 ; 
 -aryl; 
 -(substituted aryl); 
 -heteroaryl; 
 -(substituted heteroaryl); 
 -heterocyclyl; 
 -(substituted heterocyclyl); 
 —CO-aryl; and 
 —CO-heteroaryl; 
 
 
         each R 3  is independently selected form the group consisting of hydrogen; C 1-10 alkyl-heteroaryl; C 1-10 alkyl-(substituted heteroaryl); C 1-10 alkyl-aryl; C 1-10 alkyl-(substituted aryl) and C 1-10 alkyl; 
         n is 0 to 4; 
         and each R present is independently selected from the group consisting of C 1-10  alkyl, C 1-10 alkoxy, halogen and trifluoromethyl, or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier. 
       
     
     
         25 . The pharmaceutical compound of claim  1  wherein
 R 4  is heterocyclyl.   
     
     
         26 . The pharmaceutical compound of claim  1  wherein
 R 4  is substituted heterocyclyl.