Prodrugs for Use as Ophthalmic Agents

Abstract

The subject invention provides a mechanism by which steroidal quinol compounds confer beneficial ophthalmic effects. The subject compounds possess a lipophilic-hydrophilic balance for transcorneal penetration and are readily reduced into parent phenolic A-ring steroid compounds to provide protection or treatment against various ocular symptoms and disorders. The compounds according to the subject invention appear to be highly advantageous as prodrugs to provide protection and/or treatment against ocular disorders. These prodrugs confer lipid solubility optimal for transocorneal penetration and are readily converted to endogenous reducing agents into active phenolic A-ring steroid compounds. To the extent that these prodrugs have reduced feminizing effects and systemic toxicity, they would be expected to be quite advantageous for protecting or treating the eye against ocular disorders such as cataract or glaucoma without undesired (systemic) side effects).

1 . A method for treating a patient diagnosed with at least one ophthalmic disorder, wherein said method comprises administering to the patient an effective amount of a steroidal quinol, wherein the steroidal quinol is converted to biologically active 2-(1-adamantyl)-estra-1,3,5(10)-triene-3,17β-diol in vivo.  
     
     
         2 . The method of  claim 1 , wherein the steroidal quinol is 2-(1-adamantyl)-10β,17β-dihydroxyestra-1,4-dien-3-one.  
     
     
         3 . The method, according to  claim 1 , further comprising administering the quinol by a route selected from the group consisting of oral, buccal, intramuscular, transdernal, intravenous, and subcutaneous.  
     
     
         4 . The method, according to  claim 1 , wherein the ophthalmic disorders are selected from the group consisting of retinitis pigmentosa, conjunctivitis, diabetic retinopathy, dry eye, macular degeneration, glaucoma, and cataracts.  
     
     
         5 . A quinol that is converted to a biologically active 2-(1-adamantyl)-estra-1,3,5(10)-triene-3,17β-diol and having the structure  
       
         
           
           
               
               
           
         
       
     
     
         6 . A biologically active compound having the structure  
       
         
           
           
               
               
           
         
       
     
     
         7 . A pharmaceutical composition comprising a quinol that is converted to a biologically active estrogen compound via enzyme catalyzed reduction, wherein said composition further comprises a pharmaceutically acceptable carrier, wherein the quinol has the structure:  
       
         
           
           
               
               
           
         
       
     
     
         8 . A pharmaceutical composition comprising a biologically active estrogen compound having the structure: