Quinazolinone compounds

Abstract

The present invention relates to quinazolinone compounds, processes for their preparation and their use as pharmaceutical agents for the treatment of Parkinson's disease (PD). The quinazolinone compounds are of general formula I

1 .- 30 . (canceled) 
     
     
         31 . A method for the treatment of neurological disorder which comprises administering to a patient in need thereof an effective amount of a compound of formula II 
       
         
           
           
               
               
           
         
         in which 
         R 1  and R 2  are independently selected from H, optionally substituted C 1-6  alkyl and optionally substituted C 2-6 alkynyl provided that at least one of R 1  and R 2  is other than H; or 
         R 1  and R 2  together with the N atom to which they are attached form an optionally substituted 5- or 6-membered heterocyclyl in which the nitrogen atom is the only ring heteroatom and which may contain at least one further ring heteroatom selected from N and O; and 
         R 3  is methylene cyclopropyl or optionally substituted C 3-6 cycloalkyl; 
         or pharmaceutically acceptable salts thereof. 
       
     
     
         32 . The method of  claim 31  wherein the neurological disorder is a movement disorder. 
     
     
         33 . The method of  claim 31  wherein the treatment of the neurological disorder includes preventing or inhibiting the depletion of dopaminergic neurons. 
     
     
         34 . The method of  claim 31  further comprising administering to said patient at least one compound selected from a dopamine replacing compound, a dopamine agonist, an MAO-B inhibitor and a COMT inhibitor. 
     
     
         35 . The method according to  claim 31 , in which the compound of formula II is any one of the following compounds: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts thereof. 
       
     
     
         36 . The method according to  claim 31 , in which the compound of formula II is any one of the following compounds: 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts thereof. 
       
     
     
         37 . The method according to  claim 31 , in which the compound of general formula II is 
       
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts thereof. 
       
     
     
         38 . The method according to  claim 31  wherein R 3  is methylene cyclopropyl. 
     
     
         39 . The method according to  claim 31  wherein, in said compound,
 R 1  is selected from H and C 1-4 alkyl; 
 R 2  is selected from C 1-4 alkyl optionally substituted with optionally substituted aryl or C 2-6 alkynyl; or 
 R 1  and R 2  together with the N atom to which they are attached form an optionally substituted 5- or 6-membered heterocyclyl which may contain at least one further ring heteroatom selected from N and O; and 
 R 3  is C 1-4 alkyl 
 or pharmaceutically acceptable salts thereof. 
 
     
     
         40 . The method according to  claim 41  in which said compound is selected from the following: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts thereof. 
       
     
     
         41 . The method according to  claim 31  in which the compound is 
       
         
           
           
               
               
           
         
         in which 
         R 1   c  is selected from H and C 1-4 alkyl; 
         R 2   c  is selected from C 1-4 alkyl, C 2-6 cycloalkyl methyl substituted with optionally substituted aryl and C 2-4 alkynyl; or 
         R 1   c  and R 2   c  together with the N atom to which they are attached form an optionally substituted 5- or 6-membered heterocyclyl which may contain at least one further heteroatom selected from N and O; and 
         R 3   c  is selected from optionally substituted C 3-6 cycloalkyl, optionally substituted aryl and optionally substituted 5- or 6-membered heterocyclyl containing at least one heteroatom selected from N and O; 
         or pharmaceutically acceptable salts thereof. 
       
     
     
         42 . The method according to  claim 31  in which the compound is selected from the following: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or pharmaceutically acceptable salts thereof.