Prostaglandin derivatives for the treatment of glaucoma or ocular hypertension

Abstract

The invention relates to ophthalmological compositions for topical treatment of glaucoma or ocular hypertension comprising an effective intraocular pressure reducing amount of a prostaglandin derivative of PGA, PGB, PGD, PGE or PGF, in which the omega chain contains a ring structure, in an ophthalmologically compatible carrier. The invention further relates to the preparation of said compositions and their use for treatment of glaucoma or ocular hypertension.

1 . Use of a therapeutically active and physiologically acceptable derivative of prostaglandin PGA, PGB, PGD, PGE or PGF, in which the omega chain has the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 C is a carbon atom (the number is indicated within parenthesis)  
 B is a single bond, a double bond or a triple bond  
 D is a chain with 1-10 carbon atoms, optionally interrupted by hetero atoms O, S, or N, the substituents on each carbon atom being H, alkyl groups, preferably lower alkyl groups with 1-5 carbon atoms, a carbonyl group, or a hydroxyl group  
 R 2  is a ring structure such as a phenyl group which is unsubstituted or has at least one substituent selected from C 1 -C 5  alkyl groups, C 1 -C 4  alkoxy groups, trifluoromethyl groups, C 1 -C 3  aliphatic acylamino groups, nitro groups, halogen atoms, and phenyl group; or an aromatic heterocyclic group having 5-6 ring atoms, like thiazol, imidazole, pyrrolidine, thiopene and oxazole; or a cycloalkane or a cycloalkene with 3-7 carbon atoms in the ring, optionally substituted with lower alkyl groups with 1-5 carbon atoms,  
 for the preparation of an ophtalmological composition for the treatment of glaucoma or ocular hypertension.  
 
     
     
         2 . Use according to  claim 1  wherein D is a chain with 2-8 carbon atoms.  
     
     
         3 . Use according to  claim 1  wherein D is a chain with 2-5 carbon atoms.  
     
     
         4 . Use according to  claim 1  wherein D is a chain with 3 carbon atoms.  
     
     
         5 . Use according to any of claims  1 - 4  wherein B is a single bond or a double bond and the substituent on C 15  being a carbonyl group or (R)—OH or (S)—OH.  
     
     
         6 . Use according to any of claims  1 - 5  wherein R 2  is a phenyl group which is unsubstituted or has at least one substituent selected from C 1 -C 5  alkyl groups, C 1 -C 4  alkoxy groups, trifluoromethyl groups, C 1 -C 3  aliphatic acylamino groups, nitro groups, halogen atoms or a phenyl group.  
     
     
         7 . Use according to  claim 6  wherein the prostaglandin derivative is a 17-phenyl-18,19,20-trinor analogue.  
     
     
         8 . Use according to  claim 7  wherein the prostaglandin derivative is a 15-dehydro-17-phenyl-18,19,20-trinor analogue or a 13,14-dihydro-17-phenyl-18,19,20-trinor analogue.  
     
     
         9 . Use according to  claim 8  wherein the prostaglandin derivative is a 13,14-dihydro-17-phenyl-18,19,20-trinor derivative of PGA, PGE or PGF.  
     
     
         10 . Use according to  claim 8  wherein the prostaglandin is a 15-dehydro-17-phenyl-18,19,20-trinor derivative of PGA, PGE or PGF.  
     
     
         11 . Use according to any of claims  1 - 10  wherein the prostaglandin derivative is an alkyl ester.  
     
     
         12 . A method for treating glaucoma or ocular hypertension in a subject's eye which comprises contacting the surface of the eye with an effective intraocular pressure reducing amount of a therapeutically active and physiologically acceptable derivative of prostaglandin PGA, PGB, PGD, PGE or PGF in which the omega chain has the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 C is a carbon atom (the number is indicated within parenthesis)  
 B is a single bond, a double bond or a triple bond  
 D is a chain with 1-10 carbon atoms, optionally interrupted by hetero atoms O, S, or N, the substituents on each carbon atom being H, alkyl groups, preferably lower alkyl groups with 1-5 carbon atoms, a carbonyl group, or a hydroxyl group  
 R 2  is a ring structure such as a phenyl group which is unsubstituted or has at least one substituent selected from C 1 -C 5  alkyl groups, C 1 -C 4  alkoxy groups, trifluoromethyl groups, C 1 -C 3  aliphatic acylamino groups, nitro groups, halogen atoms, and phenyl group; or an aromatic heterocyclic group having 5-6 ring atoms, like thiazol, imidazole, pyrrolidine, thiopene and oxazole; or a cycloalkane or a cycloalkene with 3-7 carbon atoms in the ring, optionally substituted with lower alkyl groups with 1-5 carbon atoms,  
 
     
     
         13 . The method of  claim 12  wherein D is chain with 2-8 carbon atoms.  
     
     
         14 . The method of  claim 12  wherein D is a chain with 2-5 carbon atoms.  
     
     
         15 . The method-of  claim 12  wherein D is a chain with 3 carbon atoms.  
     
     
         16 . The method of any of claims  12 - 15  wherein B is a single bond or a double bond and the substituent on C 15  being a carbonyl group or (R)—OH or (S)—OH.  
     
     
         17 . The method of any of claims  12 - 16  wherein R 2  is a phenyl group which is unsubstituted or has at least one substituent selected from C 1 -C 5  alkyl groups; C 1 -C 4  alkoxy groups, trifluoromethyl groups, C 1 -C 3  aliphatic acylamino groups, nitro groups, halogen atoms or a phenyl group.  
     
     
         18 . The method of  claim 17  wherein the prostaglandin derivative is a 17-phenyl-18,19,20-trinor analogue.  
     
     
         19 . The method of  claim 18  wherein the prostaglandin derivative is a 15-dehydro-17-phenyl-18,19,20-trinor analogue or a 13,14-dihydro-17-phenyl-18,19,20-trinor analogue.  
     
     
         20 . The method of  claim 19  wherein the prostaglandin derivative is a 15-dehydro-17-phenyl-18,19,20-trinor derivative of PGA, PGE or PGF.  
     
     
         21 . The method of  claim 20  wherein the prostaglandin derivative is a 13,14-dihydro-17-phenyl-18,19-20-trinor derivative of PGA, PGE or PGF.  
     
     
         22 . The method of any of claims  12 - 21  wherein the prostaglandin derivative is an alkyl ester.  
     
     
         23 . An ophthalmological composition for topical treatment of glaucoma or ocular hypertension which comprises an effective intraocular pressure reducing amount of a therapeutically active and physiologically acceptable prostaglandin derivative of PGA, PGB, PGD, PGE or PGF in which the omega chain has the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 C is a carbon atom (the number is indicated within parenthesis)  
 B is a single bond, a double bond or a triple bond  
 D is a chain with 1-10 carbon atoms, optionally interrupted by hetero atoms O, S, or N, the substituents on each carbon atom being H, alkyl groups, preferably lower alkyl groups with 1-5 carbon atoms, a carbonyl group, or a hydroxyl group  
 R 2  is a ring structure such as a phenyl group which is unsubstituted or has at least one substituent selected from C 1 -C 5  alkyl groups, C 1 -C 4  alkoxy groups trifluoromethyl groups, C 1 -C 3  aliphatic acylamino groups, nitro groups, halogen atoms, and phenyl group; or an aromatic heterocyclic group having 5-6 ring atoms, like thiazol, imidazole, pyrrolidine, thiopene and oxazole; or a cycloalkane or a cycloalkene with 3-7 carbon atoms in the ring, optionally substituted with lower alkyl groups with 1-5 carbon atoms,  
 in an ophthalmologically compatible carrier.