Compounds for treating ophthalmic diseases and disorders

Abstract

Provided are compounds, pharmaceutical compositions thereof, and methods of treating ophthalmic diseases and disorders, such as age-related macular degeneration and Stargardt's Disease, using said compounds and compositions.

1 .- 98 . (canceled) 
     
     
         99 . A compound of Formula (I) or tautomer, stereoisomer, geometric isomer or a pharmaceutically acceptable salt or N-oxide thereof: 
       
         
           
           
               
               
           
         
       
       wherein,
 Z is —C(R 9 )(R 10 )—C(R 1 )(R 2 )—; 
 G is selected from —N(R 42 )C(═O)—R 40 , or —N(R 42 )—C(R 42 )(R 42 )—R 40 ; 
 R 40  is selected from —C(R 16 )(R 17 )(R 18 ); 
 each R 42  is hydrogen; 
 R 1  and R 2  are each independently selected from hydrogen, halogen, C 1 -C 5  alkyl; or R 1  and R 2  together form an oxo; 
 R 3  and R 4  are each hydrogen; 
 R 9  is OR 19 ; 
 R 10  is each is selected from hydrogen, halogen, C 1 -C 5  alkyl or —OR 19 ; or R 9  and R 10  form an oxo; 
 R 11  is hydrogen and R 12  is hydrogen, —CH 3 , or —C(═O)R 23 ; 
 R 23  is C 1 -C 5  alkyl; 
 R 19  and R 34  are each independently hydrogen or C 1 -C 5  alkyl; 
 R 16  and R 17  are each independently selected from hydrogen, C 1 -C 5  alkyl, or halo; 
 R 18  is selected from hydrogen, C 1 -C 5  alkyl, alkoxy, hydroxy, halo or fluoroalkyl; 
 each R 33  is independently selected from halogen, OR 34 , C 1 -C 5  alkyl, or fluoroalkyl; and n is 0, 1, or 2. 
 
     
     
         100 . The compound of  claim 99  wherein,
 G is selected from —N(R 42 )C(═O)—R 40 ; and R 10  is hydrogen. 
 
     
     
         101 . The compound of  claim 99  wherein,
 G is selected from —N(R 42 )C(═O)—R 40 ; and R 9  and R 10  form an oxo. 
 
     
     
         102 . The compound of  claim 100  wherein,
 R 11  and R 12  are each hydrogen; and n is 0. 
 
     
     
         103 . The compound of  claim 101  wherein,
 R 11  and R 12  are each hydrogen; and n is 0. 
 
     
     
         104 . The compound of  claim 102  wherein,
 R 16  and R 17  are each independently selected from hydrogen or C 1 -C 5  alkyl; and 
 R 18  is selected from hydrogen, C 1 -C 5  alkyl, alkoxy, or hydroxyl. 
 
     
     
         105 . The compound of  claim 103  wherein,
 R 16  and R 17  are each independently selected from hydrogen, C 1 -C 5  alkyl; and 
 R 18  is selected from hydrogen, C 1 -C 5  alkyl, alkoxy, or hydroxyl. 
 
     
     
         106 . The compound of  claim 99  wherein,
 G is selected from —N(R 42 )—C(R 42 )(R 42 )—R 40 ; and R 10  is hydrogen. 
 
     
     
         107 . The compound of  claim 99  wherein,
 G is selected from —N(R 42 )—C(R 42 )(R 42 )—R 40 ; and R 9  and R 10  form an oxo. 
 
     
     
         108 . The compound of  claim 106  wherein,
 R 11  and R 12  are each hydrogen; and n is 0. 
 
     
     
         109 . The compound of  claim 100  wherein,
 R 11  and R 12  are each hydrogen; and n is 0. 
 
     
     
         110 . The compound of  claim 108  wherein,
 R 11  and R 12  are each hydrogen; and n is 0. 
 
     
     
         111 . The compound of  claim 109  wherein,
 R 11  and R 12  are each hydrogen; and n is 0. 
 
     
     
         112 . The compound of  claim 110  wherein,
 R 16  and R 17  are each independently selected from hydrogen, —C 1 -C 5  alkyl; and 
 R 18  is selected from hydrogen, C 1 -C 5  alkyl, alkoxy, or hydroxyl. 
 
     
     
         113 . The compound of  claim 111  wherein,
 R 16  and R 17  are each independently selected from hydrogen, C 1 -C 5  alkyl; and 
 R 18  is selected from hydrogen, C 1 -C 5  alkyl, alkoxy, or hydroxyl. 
 
     
     
         114 . A compound chosen from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         115 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of  claim 99  or a tautomer, stereoisomer, geometric isomer, pharmaceutically acceptable salt, or N-oxide thereof. 
     
     
         116 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of  claim 114  or a tautomer, stereoisomer, geometric isomer, pharmaceutically acceptable salt, or N-oxide thereof.