Management of Ophthalmologic Disorders, Including Macular Degeneration

Abstract

A drag may be used in the preparation of a medicament for the treatment or prevention of an ophthalmologic disorder, wherein the drug inhibits, antagonizes, or short-circuits the visual cycle at a step of the visual cycle that occurs outside a disc of a rod photoreceptor cell.

1 . A compound of formula XI: 
       
         
           
           
               
               
           
         
         wherein, independently for each occurrence, 
         n is 0 to 10 inclusive; 
         R 1  is hydrogen or alkyl; 
         R 2  is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, or aralkyl; 
         Z is cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, aralkyl, —C(═O)R b , or —(CH 2 ) p R b ; 
         p is 0 to 20 inclusive; 
         R a  is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, or aralkyl; 
         R b  is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, or aralkyl; and 
            denotes a single bond or a trans double bond; 
         provided that the compound is not N-(4-hydroxyphenyl)retinamide. 
       
     
     
         2 . The compound of  claim 1 , wherein R 1  is hydrogen or methyl. 
     
     
         3 . The compound of  claim 1 , wherein Z is aryl. 
     
     
         4 . The compound of  claim 1 , wherein R a  is hydrogen. 
     
     
         5 . A compound of  claim 1 , wherein said compound of formula XI is a compound of formula XIa: 
       
         
           
           
               
               
           
         
         wherein, independently for each occurrence, 
         n is 0 to 10 inclusive; 
         R 1  is hydrogen or alkyl; 
         R 2  is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, or aralkyl; 
         R 3 , R 4 , R 5 , R 6  and R 7  are hydrogen, halogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aralkyenyl, aralkynyl, heteroaralkyl, heteroaralkyenyl, heteroaralkynyl, cyano, nitro, sulfhydryl, hydroxyl, sulfonyl, amino, acylamino, amido, alkylthio, carboxyl, carbamoyl, alkoxyl, sulfonate, sulfate, sulfonamido, sulfamoyl, sulfonyl, or sulfoxido; 
         R a  is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, or aralkyl; and 
            denotes a single bond or a trans double bond; 
         provided that the compound is not N-(4-hydroxyphenyl)retinamide. 
       
     
     
         6 . The compound of  claim 5 , wherein R 1  is hydrogen or methyl. 
     
     
         7 . The compound of  claim 5 , wherein R a  is hydrogen. 
     
     
         8 . The compound of  claim 5 , wherein R 3 , R 4 , R 6  and R 7  are hydrogen. 
     
     
         9 . The compound of  claim 5 , wherein R 5  is hydroxyl. 
     
     
         10 . A compound of  claim 1 , wherein said compound of formula XI is a compound of formula XIb: 
       
         
           
           
               
               
           
         
         wherein, independently for each occurrence, 
         n is 0 to 5 inclusive; 
         R 1  is hydrogen or methyl; 
         R 2  is hydrogen, alkyl, alkenyl, alkynyl, aryl, 
       
       
         
           
           
               
               
           
         
         R 3 , R 4 , R 5 , R 6 , R 7  and R 8  are hydrogen, halogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aralkyenyl, aralkynyl, heteroaralkyl, heteroaralkyenyl, heteroaralkynyl, cyano, nitro, sulfhydryl, hydroxyl, sulfonyl, amino, acylamino, amido, alkylthio, carboxyl, carbamoyl, alkoxyl, sulfonate, sulfate, sulfonamido, sulfamoyl, sulfonyl, or sulfoxido; 
         any two geminal R 8  and the carbon to which they are bound may represent C(═O); and 
         R a  is hydrogen, alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, aryl, or aralkyl; 
         provided that the compound is not N-(4-hydroxyphenyl)retinamide. 
       
     
     
         11 . The compound of  claim 10 , wherein R 1  is hydrogen or methyl. 
     
     
         12 . The compound of  claim 10 , wherein R a  is hydrogen. 
     
     
         13 . The compound of  claim 10 , wherein R 3 , R 4 , R 6  and R 7  are hydrogen. 
     
     
         14 . The compound of  claim 10 , wherein R 5  is hydroxyl. 
     
     
         15 . The compound of  claim 10 , wherein n is 1 to 3 inclusive. 
     
     
         16 . The compound of  claim 10 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 10 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 10 , wherein R 2  is 
       
         
           
           
               
               
           
         
       
     
     
         19 . A compound of formula IV: 
       
         
           
           
               
               
           
         
         wherein, independently for each occurrence, 
         n is 1, 2, 3 or 4; 
         X is —O—, —NR a —, —C(R b ) 2 - or —C(═O)—; 
         Z is —C(═O)R b , —OR b , —N(R b ) 2 , alkyl or haloalkyl; 
         R a  is hydrogen, alkyl, haloalkyl, aryl or aralkyl; and 
         R b  is hydrogen, alkyl, haloalkyl, aryl or aralkyl. 
       
     
     
         20 . A compound having a structure represented by 
       
         
           
           
               
               
           
         
       
     
     
         21 . A formulation comprising a compound defined by  claim 1 , and a second compound, different from the first compound, wherein said second compound is selected from compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, or X. 
     
     
         22 - 27 . (canceled) 
     
     
         28 . A formulation comprising a compound defined by  claim 19 , and a second compound, different from the first compound, wherein said second compound is selected from compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, or X. 
     
     
         29 . A formulation comprising a compound defined by  claim 20 , and a second compound, different from the first compound, wherein said second compound is selected from compounds of formula I, II, III, IV, V, VI, VII, VIII, IX, or X. 
     
     
         30 . A method for treating or preventing an opthalmologic disorder in a subject comprising administering to a subject a pharmaceutically acceptable amount of a compound of  claim 1 . 
     
     
         31 . A method for treating or preventing an opthalmologic disorder in a subject comprising administering to a subject a pharmaceutically acceptable amount of a compound of  claim 19 . 
     
     
         32 . A method for treating or preventing an opthalmologic disorder in a subject comprising administering to a subject a pharmaceutically acceptable amount of a compound of  claim 20 .