Non-retinoid antagonists for treatment of age-related macular degeneration and stargardt disease

Abstract

A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in mammals afflicted therewith, comprising administering to the mammal an effective amount of a non-retinoid antagonist compound or a pharmaceutically acceptable salt thereof.

1 . A method for treating a disease characterized by excessive lipofuscin accumulation in the retina in mammal afflicted therewith, comprising administering to the mammal an effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
         wherein 
         n=2 or 3; 
         R 1  is absent or present and when present, is CH 3  or O; 
         α is absent or present,
 wherein when α present, then R 1  is O, and when α is absent, then R 1  is CH 3 ; 
 
       
       
         
           
           
               
               
           
         
         Y is N or C; 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       and
 when n=2, R 1  is absent, X is 
 
       
         
           
           
               
               
           
         
       
       and Y is C,
 then z s other than 
 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the compound has the structure 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 1  wherein the disease is further characterized by bisretinoid-mediated macular degeneration. 
     
     
         4 . The method of  claim 3 , wherein the amount of the compound is effective to lower the serum concentration of RE24 in the mammal. 
     
     
         5 . The method of  claim 3 , wherein the amount of the compound is effective to lower the retinal concentration of a bisretinoid in lipofuscin in the mammal. 
     
     
         6 . The method of  claim 3 , wherein the bisretinoid is A2E. 
     
     
         7 . The method of  claim 3 , wherein the bisretinoid is isoA2E. 
     
     
         8 . The method of  claim 3 , wherein the bisretinoid is A2-DHP-PE. 
     
     
         9 . The method of  claim 3 , wherein the bisretinoid is atRAL di-PE. 
     
     
         10 . The method of  claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Age-Related Macular Degeneration. 
     
     
         11 . The method of  claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is dry (atrophic) Age-Related Macular Degeneration. 
     
     
         12 . The method of  claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Stargardt Disease. 
     
     
         13 . The method of  claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Best disease. 
     
     
         14 . The method of  claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is adult vitelliform maculopathy. 
     
     
         15 . The method of  claim 3 , wherein the disease characterized by excessive lipofuscin accumulation in the retina is Stargardt-like macular dystrophy.