Compounds and methods for the treatment of ocular disorders

Abstract

Described herein are compositions and methods for the treatment of ocular surface disorders including meibomian gland dysfunction, blepharitis, dry eye disease and other inflammatory/infections disease of the anterior surface of the eye. Said compositions and methods comprise keratolytic conjugate which demonstrate keratolytic activity, and anti-inflammatory or other desirable activities. Topical administration of said compositions to the eye, ocular surface or surrounding areas provides therapeutic benefit to patients suffering from ocular surface disorders.

1 - 31 . (canceled) 
     
     
         32 . A pharmaceutical composition comprising a compound having the structure of Formula (II): 
       
         
           
           
               
               
           
         
         wherein,
 Z is —O— or —(CR 8 R 9 ) m —; 
 m is 1-6; 
 R 8  and R 9  are each independently H, halo, alkoxy, alkyl, heteroalkyl, or haloalkyl; 
 R 10  is substituted alkyl or optionally substituted heteroalkyl, 
 or a pharmaceutically acceptable salt or solvate thereof. 
 
       
     
     
         33 - 38 . (canceled) 
     
     
         39 . The pharmaceutical composition of  claim 32 , wherein R 10  is, 
       
         
           
           
               
               
           
         
       
       or 
       
         
           
           
               
               
           
         
       
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . The pharmaceutical composition of  claim 32 , wherein R 10  is substituted alkyl. 
     
     
         43 . The pharmaceutical composition of  claim 32 , wherein R 10  is substituted heteroalkyl. 
     
     
         44 . The pharmaceutical composition of  claim 32 , wherein m is 1-3. 
     
     
         45 . The pharmaceutical composition of  claim 39 , wherein R 10  is: 
       
         
           
           
               
               
           
         
       
     
     
         46 . The pharmaceutical composition of  claim 45 , wherein Z is —(CR 8 R 9 ) m —. 
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein Z is —(CR 8 R 9 ) m —, R 8  is alkyl, R 9  is hydrogen, m is 1, and R 10  is: 
       
         
           
           
               
               
           
         
       
     
     
         48 . The pharmaceutical composition of  claim 47 , having the structure: 
       
         
           
           
               
               
           
         
       
     
     
         49 . The pharmaceutical composition of  claim 39 , wherein R 10  is: 
       
         
           
           
               
               
           
         
       
     
     
         50 . The pharmaceutical composition of  claim 49 , wherein Z is —(CR 8 R 9 ) m —. 
     
     
         51 . The pharmaceutical composition of  claim 50 , wherein Z is —(CR 8 R 9 ) m —, R 8  and R 9  are each hydrogen, m is 1, and R 10  is 
       
         
           
           
               
               
           
         
       
     
     
         52 . The pharmaceutical composition of  claim 51 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
       
     
     
         53 . The pharmaceutical composition of  claim 32 , wherein the pharmaceutical composition is an ophthalmic pharmaceutical composition. 
     
     
         54 . The pharmaceutical composition of  claim 53 , wherein the ophthalmic pharmaceutical composition is suitable for administration in an eye drop. 
     
     
         55 . The pharmaceutical composition of  claim 53 , wherein the ophthalmic pharmaceutical composition is suitable for periocular administration. 
     
     
         56 . The pharmaceutical composition of  claim 32 , wherein the pharmaceutical composition is a dermal pharmaceutical composition.