Pyrazolopyrimidine compounds

Abstract

Compounds of formula (I) and salts thereof: wherein R 1 is n-C 1-6 alkyl or C 1-2 alkoxyC 1-2 alkyl-, R 2 is halo, OH or C 1-3 alkyl, m is an integer having a value of 4, 5, 6 or 7, n is an integer having a value of 0, 1, 2 or 3, and p is an integer having a value of 0, 1 or 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 salt thereof: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is n-C 3-6 alkyl or C 1-2 alkoxyC 1-2 alkyl-; 
         each R 2  independently represents halo, OH or C 1-3 alkyl; 
         m is an integer having a value of 4, 5, 6 or 7; 
         n is an integer having a value of 0, 1, 2 or 3; 
         p is an integer having a value of 0, 1 or 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 2-methoxyethyl. 
     
     
         4 . The method according to  claim 1  wherein m is an integer having a value of 5 or 6. 
     
     
         5 . The method according to  claim 1  wherein n is 1. 
     
     
         6 . The method according to  claim 1  wherein n is 2. 
     
     
         7 . The method according to  claim 1  wherein p is 0 or 1. 
     
     
         8 . The method according to  claim 1  wherein each R 2  independently represents halo or OH. 
     
     
         9 . The method according to  claim 1  wherein each R 2  independently represents F or OH. 
     
     
         10 . The method according to  claim 1  wherein the compound is selected from the group consisting of:
 5-Butyl-3-(6-(piperidin-1-yl)hexyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-(2-Methoxyethyl)-3-(6-(piperidin-1-yl)hexyl)-1 H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-Butyl-3-(6-(pyrrolidin-1-yl)hexyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-(2-Methoxyethyl)-3-(6-(pyrrolidin-1-yl)hexyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-Butyl-3-(5-(piperidin-1-yl)pentyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-Butyl-3-(5-(pyrrolidin-1-yl)pentyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-Butyl-3-(7-(piperidin-1-yl)heptyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 5-Butyl-3-(7-(pyrrolidin-1-yl)heptyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 3-(6-(Azepan-1-yl)hexyl)-5-butyl-1H-pyrazolo[4, 3-d]pyrimidin-7-amine; 
 3-(5-(Azepan-1-yl)pentyl)-5-butyl-1H-pyrazolo[4, 3-d]pyrimidin-7-amine; 
 (S)-5-Butyl-3-(6-(3-fluoropyrrolidin-1-yl)hexyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 (S)-5-Butyl-3-(5-(3-fluoropyrrolidin-1-yl)pentyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 (R)-5-Butyl-3-(6-(3-fluoropyrrolid in-1 -yl)hexyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine formate; 
 (R)-5-Butyl-3-(5-(3-fluoropyrrolidin-1-yl)pentyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 1-(6-(7 -Amino-5-butyl-1H-pyrazolo[4,3-d]pyrimidin-3-yl)hexyl)piperidin-4-ol; 
 1-(5-(7-Amino-5-butyl-1H-pyrazolo[4, 3-d]pyrimidin-3-yl)pentyl)piperidin-4-ol; 
 5-Butyl-3-(6-(4-fluoropiperidin-1-yl)hexyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine; 
 and 5-Butyl-3-(5-(4-fluoropiperidin-1-yl)pentyl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine. 
 
     
     
         11 . The method according to  claim 1  wherein the compound is 5-Butyl-3-(6-(pyrrolidin-1-yl)hexyl)-1H-pyrazolo[4, 3-d]pyrimidin-7-amine, of formula: 
       
         
           
           
               
               
           
         
       
     
     
         12 . The method according to  claim 1  wherein the compound is in the form of a pharmaceutically acceptable salt or in the form of a free base. 
     
     
         13 . The method according to  claim 1  wherein the allergic disease, inflammatory disease, or autoimmune disease is asthma. 
     
     
         14 . The method according to  claim 1  wherein the allergic disease, inflammatory disease, or autoimmune disease is allergic rhinitis. 
     
     
         15 . 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. 
     
     
         16 . The method according to  claim 11  wherein the compound is in the form of a pharmaceutically acceptable salt. 
     
     
         17 . The method according to  claim 11  wherein the compound is in the form of a free base. 
     
     
         18 . The method according to  claim 11  wherein the allergic disease, inflammatory disease, or autoimmune disease is asthma. 
     
     
         19 . The method according to  claim 11  wherein the allergic disease, inflammatory disease, or autoimmune disease is allergic rhinitis. 
     
     
         20 . The method according to  claim 11  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.