2-Thioxanthine Derivatives Acting as MPO-Inhibitors

Abstract

The present invention relates to a compound according to Formula (I) wherein R 1 is selected from C 1 -C 6 alkyl, and said C 1 -C 6 alkyl is substituted with C 1 -C 6 alkoxy; and at least one of said C 1 -C 6 alkyl or said C 1 -C 6 alkoxy is branched; or a pharmaceutically acceptable salt thereof, solvate or solvate of a salt thereof, to compositions containing the compound and the use thereof in therapy.

1 . A compound according to Formula (I) 
     
       
         
         
             
             
         
       
       wherein: 
       R 1  is selected from C 1 -C 6  alkyl, and said C 1 -C 6  alkyl is substituted with C 1 -C 6  alkoxy; 
       and at least one of said C 1 -C 6  alkyl or said C 1 -C 6  alkoxy is branched; 
       or a pharmaceutically acceptable salt thereof, solvate or solvate of a salt thereof. 
     
   
   
       2 . A compound according to  claim 1 , wherein the C 1 -C 6  alkyl of R 1  is C 2-4 alkyl. 
   
   
       3 . A compound according to  claim 1 , wherein said C 1 -C 6  alkyl is selected from isobutyl, ethyl and propyl. 
   
   
       4 . A compound according to  claim 1 , wherein said C 1 -C 6  alkyl is substituted with C 1-3  alkoxy. 
   
   
       5 . A compound according to  claim 1 , wherein said C 1 -C 6  alkyl is substituted with C 1 -alkoxy. 
   
   
       6 . A compound according to  claim 1 , wherein said C 1 -C 6  alkyl is substituted with C 2 -alkoxy. 
   
   
       7 . A compound according to  claim 1 , wherein said alkyl is substituted with propoxy or iso-propoxy. 
   
   
       8 . A compound selected from: 
     3-(2-Ethoxy-2-methylpropyl)-2-thioxanthine; 
     3-(2-Propoxy-2-methylpropyl)-2-thioxanthine; 
     3-(2-Methoxy-2-methylpropyl)-2-thioxanthine; 
     3-(2-isopropoxyethyl)-2-thioxanthine; 
     3-(2-Ethoxypropyl)-2-thioxanthine; 
     3-(2S-Ethoxypropyl)-2-thioxanthine; and 
     3-(2R-Ethoxypropyl)-2-thioxanthine; 
     or a pharmaceutically acceptable salt, solvate or solvate of a salt thereof. 
   
   
       9 - 10 . (canceled) 
   
   
       11 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, optionally in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. 
   
   
       12 . A pharmaceutical composition comprising a compound according to  claim 8 , or a pharmaceutically acceptable salt thereof, optionally in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier. 
   
   
       13 . A method of treating or reducing the risk of, diseases or conditions in which inhibition of the enzyme MPO is beneficial, comprising administering to a person suffering from or at risk of, said disease or condition, a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
   
   
       14 . A method of treating, or reducing the risk of, diseases or conditions in which inhibition of the enzyme MPO is beneficial comprising administering to a person suffering from or at risk of, said disease or condition, a therapeutically effective amount of a compound as defined in  claim 8 , or a pharmaceutically acceptable salt thereof. 
   
   
       15 . A method of treating, or reducing the risk of inflammatory disorders, comprising administering to a person suffering from or at risk of, said disease or condition, a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
   
   
       16 . A method of treating, or reducing the risk of inflammatory disorders which comprises administering to a person suffering from or at risk of, said disease or condition, a therapeutically effective amount of a compound as defined in  claim 8 , or a pharmaceutically acceptable salt thereof. 
   
   
       17 . The method according to  claim 15  or  claim 16 , wherein said inflammatory disorders are neuroinflammatory disorders. 
   
   
       18 . The method according to  claim 17 , wherein said neuroinflammatory disorder is multiple sclerosis. 
   
   
       19 . The method according to  claim 17 , wherein said neuroinflammatory disorder is Parkinson's disease. 
   
   
       20 . A method according to  claim 14  or  claim 15 , wherein said disease or condition is cardio- and cerebrovascular atherosclerotic disorders or peripheral artery disease, heart failure or respiratory disorders. 
   
   
       21 . The method according to  claim 20 , wherein said cardiovascular atherosclerotic disorder is atherosclerosis. 
   
   
       22 . The method according to  claim 20 , wherein said respiratory disorder is chronic obstructive pulmonary disease (COPD). 
   
   
       23 . The method according to  claim 18 , wherein said respiratory disorder is selected from bronchitis; emphysema; bronchiectasis; and cystic fibrosis. 
   
   
       24 . A method of treating, or reducing the risk of stroke, comprising administering to a person suffering from or at risk of said stroke a therapeutically effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
   
   
       25 . A method of treating, or reducing the risk of stroke, comprising administering to a person suffering from or at risk of said stroke, a therapeutically effective amount of a compound according to  claim 8 , or a pharmaceutically acceptable salt thereof. 
   
   
       26 - 30 . (canceled)