Compound for the prophylaxis or treatment of organ damage

Abstract

The present invention relates to compounds for prophylaxis or treatment of organ damage by restoring endothelial function and/or inhibiting reactive oxygen species production and especially to compounds for prophylaxis or treatment of diabetic kidney damage. Specifically, the present invention relates to 6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)(piperazin-1-yl)methanone or N,6-dihydroxy-2,5,7,8-tetramethylchroman-2-carboxamide or a pharmaceutically acceptable salt or base thereof for use in the prophylaxis or treatment of organ damage by restoring endothelial function and/or inhibiting reactive oxygen species production and especially diabetic kidney organ damage.

1 . A method of treating or prophylaxis of organ damage in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to formula (I) or a pharmaceutically salt thereof: 
       
         
           
           
               
               
           
         
         wherein R1 is a C 1 -C 4  linear or branched alkyl group; 
         wherein R2 is a C 1 -C 4  linear or branched alkyl group; 
         wherein R3 is a hydrogen or R3 forms together with the 6-oxygen an ester group; 
         n is 0 or 1; 
         R4 is —C(═O)—N—R5, wherein R5 is an alkyl group, and wherein the alkyl group comprises 1-12 carbon atoms and may further comprise one or more nitrogen atoms and/or one or more oxygen atoms, 
         wherein R5 does not comprise an aromatic heterocycle ring; 
         wherein the molecular weight of R4 preferably is less than 300 Da; 
         wherein the endothelial function is restored and/or production of reactive oxygen species is inhibited, thereby treating or prophylaxis of the organ damage. 
       
     
     
         2 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein R3 is hydrogen. 
     
     
         3 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein the compound according to formula (I) has a molecular weight lower than 500 Da. 
     
     
         4 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein the alkyl group in R5 is linear, branched or cyclic. 
     
     
         5 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein R3 forms together with the 6-oxygen an ester group and has 1 to 12 carbon atoms and comprises one or more amine or oxygen atoms. 
     
     
         6 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein R5 is an alkyl group substituted with nitrogen and/or oxygen. 
     
     
         7 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein the alkyl group in R5 comprises at least one cyclic structure. 
     
     
         8 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein the organ damage is diabetic kidney damage. 
     
     
         9 . The method of treating or prophylaxis of organ damage according to  claim 1 , wherein said organ damage is diabetic nephropathy. 
     
     
         10 . A method of treating or prophylaxis of organ damage in a subject, comprising administering to the subject a therapeutically effective amount of a compound according to formula (I) or a pharmaceutically salt thereof: 
       
         
           
           
               
               
           
         
         wherein R1 is a C 1 -C 4  linear or branched alkyl group; 
         wherein R2 is a C 1 -C 4  linear or branched alkyl group; 
         wherein R3 is a hydrogen; 
         n is 0 or 1; 
         R4 is —C(═O)—NH—R5, wherein R5 is an alkyl group, wherein the alkyl group comprises 1-12 carbon atoms and further comprises at least one nitrogen atom; 
         wherein the molecular weight of R4 preferably is less than 300 Da; 
         wherein R5 comprises a cyclic structure; 
         wherein R5 does not comprise an aromatic heterocycle ring; 
         wherein the endothelial function is restored and/or production of reactive oxygen species is inhibited, thereby treating or prophylaxis of the organ damage. 
       
     
     
         11 . The method of treating or prophylaxis of organ damage according to  claim 10 , wherein the cyclic structure in R5 is a heterocyclic structure comprising a nitrogen atom.