2-Pyrrolidinone derivatives substituted at position 4 for reducing the extracellular glutamate level

Abstract

2-pyrrolidinone derivatives which have in position 4 at least one substituent are described herein. Methods of treating polyglutamine disorders such as Huntington's disease, dentorubropallidoluysian atrophy (DRPLA), spinal and bulbar muscular atrophy (SBMA), and spinocerebellar ataxias with 2-pyrrolidinone derivatives are also descibed.

1 - 11 . (canceled)  
   
   
       12 . A method of treating acute and chronic glaucoma comprising, administering to a subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a 2-pyrrolidinone derivative of the general formula  
     
       
         
         
             
             
         
       
     
     in which 
 R 1  and R 2  are, independently of one another, hydrogen atoms, hydroxyl groups, amino groups, C 1 -C 10  alkoxy radicals, C 1 -C 10  alkyl radicals or C 1 -C 10  alkyl-amino radicals, or R 1  and R 2  together with the carbon atom in position 4 of the pyrrolidinone ring form a five- to ten-membered saturated or unsaturated ring which, besides carbon atoms, may have up to 2 heteroatoms selected from oxygen, sulfur and nitrogen atoms, and which is unsubstituted or is substituted by up to 3 substituents selected from hydroxyl groups, amino groups, C 1 -C 4  alkyl radicals, C 1 -C 4  alkoxy radicals and C 1 -C 4  alkylamino radicals, with the proviso that R 1  and R 2  are not both hydrogen atoms,  
 R 3 , R 4 , R 5  and R 6  are, each independently of one another, hydrogen atoms, halogen atoms, hydroxyl groups, amino groups, C 1 -C 10  alkyl radicals, C 1 -C 10  alkoxy radicals, C 1 -C 10  alkylamino radicals or C 6 -C 10  aryl radicals, and  
 R 7  is a hydrogen atom or a C 1 -C 10  aryl radical or C 1 -C 10  acyl radical,  
 or a pharmacologically acceptable salt thereof or prodrug thereof.  
 
   
   
       13 . The method of  claim 12 , wherein in the pyrrolidinone derivative, the radicals R 3 , R 4 , R 5  and R 6  are hydrogen atoms.  
   
   
       14 . The method of  claim 12 , wherein in the 2-pyrrolidinone derivative, one of the radicals R 1  and R 2  is a hydrogen atom, and the other radical is a C 1  to C 10  alkyl radical.  
   
   
       15 . The method of  claim 12 , wherein in the 2-pyrrolidinone derivative, the radicals R 1  and R 2  form, together with the carbon atom in position 4 of the pyrrolidinone ring, a six-membered saturated hydrocarbon ring.  
   
   
       16 . The method of  claim 12 , wherein said 2-pyrrolidinone derivative comprises 8-azaspiro[5,4]decan-9-one.