Cyclopentane heptan(ene)oic acid, 2-heteroarylalkenyl derivatives as therapeutic agents

Abstract

The invention relates to the use of derivatives of F-type prostaglandins as ocular hypotensives. The PGF derivatives used in accordance with the invention are represented by the following formula I: wherein wavy line attachments indicate either the alpha (α) or beta (β) configuration; dashed bonds represent a double bond, or a single bond, R is a substituted heteroaryl radical, R 1 is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 , R 1 is hydrogen or a lower alkyl radical having up to six carbon 20 atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 and —N(R 5 )SO 2 R 6 , wherein R 5 represents hydrogen or CH 2 OR 6 and R 6 represents hydrogen or a lower alkyl radical having up to six carbon atoms and halogen substituted derivatives of said lower alkyl radical, e.g. a fluoro substituted lower alkyl radical; Y is ═O or represents 2 hydrogen radicals. Certain of the compounds represented by Formula I comprise another aspect of the present invention.

1 . A method of treating ocular hypertension which comprises administering to a mammal having ocular hypertension a therapeutically effective amount of a compound represented by formula II:  
       
         
           
           
               
               
           
         
       
       wherein the hatched segments represent a bonds, the solid triangle represents a β bond, wavy line attachments indicate either the alpha (α) or beta (β) configuration; dashed bonds represent a double bond or a single bond, R is a substituted hetero aryl radical, R 1  is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 , and —N(R 5 )SO 2 R 6 , wherein R 5  represents hydrogen or CH 2 OR 6  and R 6  represents hydrogen or a lower alkyl radical having up to six carbon atoms and halogen substituted derivatives of said lower alkyl radical; Y is ═O or represents 2 hydrogen radicals and the pharmaceutically acceptable salts and esters thereof.  
     
     
         2 . The method of  claim 1  wherein the substituent on the heteroaryl radical is selected from the group consisting of lower alkyl, halogen, trifluoromethyl, COR 1 , COCF 3 , SO 2 NR 1 , SO 2 NH 2 , NO 2  and CN.  
     
     
         3 . A pharmaceutical product, comprising a container adapted to dispense the contents of said container in metered form; and an ophthalmic solution in said container comprising a compound of formula I as defined in  claim 1 , or a pharmaceutically acceptable salt thereof, in admixture with a non-toxic, ophthalmically acceptable liquid vehicle.  
     
     
         4 . A method of treating glaucoma which comprises administering to a mammal having glaucoma a therapeutically effective amount of a compound represented by formula I:  
       
         
           
           
               
               
           
         
       
       wherein the wavy segments represent either an alpha (α) or beta (β) bond; dashed bonds represent a double bond or a single bond, R is a substituted hetero aryl radical, R 1  is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 , R 1  is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 , and —N(R 5 )SO 2 R 6 , wherein R 5  represents hydrogen or CH 2 OR 6  and R 6  represents hydrogen or a lower alkyl radical having up to six carbon atoms and halogen substituted derivatives of said lower alkyl radical; Y is ═O or represents 2 hydrogen radicals and the pharmaceutically acceptable salts and esters thereof.  
     
     
         5 . The method of  claim 4  wherein said compound is represented by formula II:  
       
         
           
           
               
               
           
         
       
       wherein the hatched segments represent α bonds and the triangular segment represents a β bond.  
     
     
         6 . A method of treating elevated intraocular pressure which comprises administering to a mammal having elevated intraocular pressure a therapeutically effective amount of a compound represented by formula I:  
       
         
           
           
               
               
           
         
       
       wherein the wavy segment represents either an alpha (α) or beta (β) bond; dashed bonds represent a double bond or a single bond, R is a substituted hetero aryl radical, R 1  is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 , R 1  is hydrogen or a lower alkyl radical having up to six carbon atoms, X is selected from the group consisting of —OR 1 , —N(R 1 ) 2 , and —N(R 5 )SO 2 R 6 , wherein R 5  represents hydrogen or CH 2 OR 6  and R 6  represents hydrogen or a lower alkyl radical having up to six carbon atoms and halogen substituted derivatives of said lower alkyl radical; Y is ═O or represents 2 hydrogen radicals and the pharmaceutically acceptable salts and esters thereof.  
     
     
         7 . The method of  claim 6  wherein said compound is represented by formula II:  
       
         
           
           
               
               
           
         
       
       wherein the hatched segments represent α bonds and the triangular segment represents a β bond.