Novel compounds

Abstract

Compounds of formula (I) and salts thereof: wherein R 1 is n-C 4-6 alkyl or C 1-2 alkoxyC 1-2 alkyl-; R 2 is hydrogen or methyl; each R 3 is hydroxy, halo or n-C 1-3 alkyl; m is an integer having a value of 2 to 4; n is an integer having a value of 0 to 3; and p is an integer having a value of 0 to 2, are inducers of human interferon. Compounds which induce human interferon may be useful in the treatment of various disorders, for example the treatment of allergic diseases and other inflammatory conditions, for example allergic rhinitis and asthma, infectious diseases and cancer, and may also be useful as vaccine adjuvants.

1 . A method of treating allergic disease, inflammatory disease, or autoimmune disease in a human in need thereof, the method comprising administering to the human a compound of formula (I) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is n-C 4-6 alkyl or C 1-2 alkoxyC 1-2 alkyl-; 
         R 2  is hydrogen or methyl; 
         each R 3  is hydroxy, halo or n-C 1-3 alkyl; 
         m is an integer having a value of 2 to 4; 
         n is an integer having a value of 0 to 3; 
         p is an integer having a value of 0 to 2; 
         and administering to the human at least one other therapeutically active agent. 
       
     
     
         2 . The method according to  claim 1  wherein R 1  is n-butyl. 
     
     
         3 . The method according to  claim 1  wherein R 1  is ethoxymethyl. 
     
     
         4 . The method according to  claim 1  wherein R 1  is 2-methoxyethyl. 
     
     
         5 . The method according to  claim 1  wherein R 2  is hydrogen. 
     
     
         6 . The method according to  claim 1  wherein R 2  is methyl. 
     
     
         7 . The method according to  claim 1  wherein n is an integer having a value of 1 or 2. 
     
     
         8 . The method according to  claim 1  wherein p is 0. 
     
     
         9 . The method according to  claim 1  wherein R 3  is hydroxy or halo. 
     
     
         10 . The method according to  claim 1  wherein p is 1 and R 3  is hydroxy or fluoro. 
     
     
         11 . The method according to  claim 1  wherein p is 2 and R 3  is fluoro. 
     
     
         12 . The method according to  claim 1  wherein the compound is selected from the group consisting of:
 2-Butyl-7-(6-(piperidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(piperidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(4-(piperidin-1-yl)butyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-(Ethoxymethyl)-7-(6-(piperidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-(2-Methoxyethyl)-7-(6-(piperidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(6-(piperidin-1-yl) hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(5-(piperidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(4-(piperidin-1-yl)butyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(pyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(6-(pyrrolidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Pentyl-7-(6-(piperidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 7-(5-(Azepan-1-yl)pentyl)-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 7-(4-(Azepan-1l-yl)butyl)-2-butyl-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(6-(pyrrolidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 7-(6-(Azetidin-1-yl)hexyl)-2-butyl-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(5-(pyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 7-(5-(Azetidin-1-yl)pentyl)-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 7-(5-(Azetidin-1-yl)pentyl)-2-butyl-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(4-(pyrrolidin-1-yl)butyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(4,4-difluoropiperidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(4-fluoropiperidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 7-(5-(4-Fluoropiperidin-1-yl)pentyl)-2-(2-methoxyethyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 1-(5-(4-Amino-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)pentyl) piperidin-4-ol; 
 (R)-2-Butyl-7-(5-(3-fluoropyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (S)-2-Butyl-7-(5-(3-fluoropyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (R)-7-(5-(3-Fluoropyrrolidin-1-yl)pentyl)-2-(2-methoxyethyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (S)-7-(5-(3-Fluoropyrrolidin-1-yl) pentyl)-2-(2-methoxyethyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (S)-1-(5-(4-Amino-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)pentyl)pyrrolidin-3-ol; 
 1-(5-(4-Amino-2-butyl-5H-pyrrolo[3,2-d]pyrimidin-7-yl)pentyl)azetidin-3-ol; 
 7-(6-(Azepan-1-yl)hexyl)-2-(2-methoxyethyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(6-(4-fluoropiperidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (R)-2-Butyl-7-(6-(3-fluoropyrrolidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (S)-2-Butyl-7-(6-(3-fluoropyrrolidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (S)-2-Butyl-7-(5-(2-methylpyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (R)-2-Butyl-7-(5-(2-methylpyrrolidin-1-yl) pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(3-methylazetidin-1l-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(3-fluoroazetidin-1l-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-6-methyl-7-(6-(pyrrolidin-1-yl)hexyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(4-fluoropiperidin-1-yl)pentyl)-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (S)-2-Butyl-7-(5-(3-fluoropyrrolidin-1-yl)pentyl)-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 (R)-2-Butyl-7-(5-(3-fluoropyrrolidin-1-yl) pentyl)-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; 
 2-Butyl-7-(5-(3-fluoroazetidin-1-yl)pentyl)-6-methyl-5H-pyrrolo[3,2-d]pyrimidin-4-amine; and 
 2-(2-Methoxyethyl)-7-(5-(pyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine. 
 
     
     
         13 . The method according to  claim 1  wherein the compound is 2-butyl-7-(5-(pyrrolidin-1-yl)pentyl)-5H-pyrrolo[3,2-d]pyrimidin-4-amine: 
       
         
           
           
               
               
           
         
       
     
     
         14 . The method according to  claim 1  wherein the compound is in the form of a pharmaceutically acceptable salt. 
     
     
         15 . The method according to  claim 1  wherein the compound is in the form of a free base. 
     
     
         16 . The method according to  claim 1  wherein the allergic disease, inflammatory disease, or autoimmune disease is asthma. 
     
     
         17 . The method according to  claim 1  wherein the allergic disease, inflammatory disease, or autoimmune disease is allergic rhinitis. 
     
     
         18 . The method according to  claim 1  wherein the at least one other therapeutically active agent is selected from an antigen immunotherapy, an anti-histamine, a steroid, an NSAID, a bronchodilator, methotrexate, a leukotriene modulator, monoclonal antibody therapy, receptor therapy, and antigen non-specific immunotherapy.