Equilenin derivatives, methods for producing the same and medicaments containing them

Abstract

Described are novel equilenin derivatives of general formula I methods for producing the same and medicaments containing these compounds. The new compounds have antioxidative activity and are usable for geroprophylaxis in women and men.

1 . Equilenin derivatives of general formula I  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  denotes a hydrogen atom, a C 1 -C 5 -alkyl group, a C 1 -C 5 -acyl group or a benzoyl group,  
 R 2  denotes a hydrogen atom and R 2 ′ denotes a hydrogen atom, a fluorine atom, a hydroxyl group or a C 1 -C 5 -acyloxy group or R 2  and R 2 ′ together denote an oxo group,  
 R 3  denotes a hydrogen atom or a methyl group,  
 R 4  denotes a hydrogen atom and R 4 ′ denotes a hydroxyl group or a C 1 -C 11 -acyloxy group or R 4  and R 4 ′ together denote an oxo group, a methylene group, a halomethylene group or a dihalo-methylene group and  
 R 5  denotes a hydrogen atom or a methyl group.  
 
     
     
         2 . Equilenin derivatives according to  claim 1 , characterized in that R 5  is a hydrogen atom.  
     
     
         3 . Equilenin derivatives according to  claim 1 , namely 
 1) 14α,15α-methylenestra-1,3,5(10),6,8-pentaene-3,11β,17β-triol,    2) 11β,17β-dihydroxy-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-3-yl benzoate,    3) 11β,17β-dihydroxy-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-3-yl propionate,    4) 3,11β-dihydroxy-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-17β-yl decanoate,    5) 3,11β-dihydroxy-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-17-one,    6) 3-methoxy-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-11α,17β-diyl diacetate,    7) 15β-methyl-14α,15α-methylenestra-1,3,5(10),6,8-pentaene-3,11β,17β-triol,    8) 11β-fluoro-14α,15α-methylenestra-1,3,5(10),6,8-pentaene-3,17β-diol,    9) 3,17β-dihydroxy-14α,15α-methylene-1,3,5(10),6,8-pentaen-11-one,    10) 3-methoxy-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-11α,17α-diyl diacetate,    11) 3-methoxy-14α,15α-methylene-11-oxoestra-1,3,5(10),6,8-pentaen-17α-yl acetate,    12) 11β-hydroxy-17,17-difluoromethylene-14α,15α-methylenestra-1,3,5(10),6,8-pentaen-3-yl benzoate, and    13) 14α,15α-17,17-bis-methylenestra-1,3,5(10),6,8-pentaene-3,11α-diol.    
     
     
         4 . Method for producing equilenin derivatives of the invention of general formula I  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 2 ′, R 3 , R 4 , R 4 ′ and R 5  have the meaning indicated in  claim 1 , by subjecting a compound of general formula II  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 2 ′, R 3 , R 4 , R 4 ′ and R 5  have the meaning indicated in  claim 1 , to reaction with diphosphorus tetraiodide in the presence of pyridine and then converting the compound thus obtained to a compound of general formula I in a manner that in itself is known.  
     
     
         5 . Pharmaceutical composition containing at least one compound of general formula I according to  claims 1  to  3 , optionally together with pharmaceutically compatible auxiliary agents and carriers.  
     
     
         6 . Use of the compounds of general formula I according to  claims 1  to  3  for geroprophylaxis in men and women.  
     
     
         7 . Compounds of general formula I according to  claims 1  to  3  for use as therapeutically active substances.  
     
     
         8 . Cyclopropano steroids of general formula II  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , R 2 ′, R 3 , R 4 , R 4 ′ and R 5  have the meaning indicated in  claim 1   
     
     
         9 . Cyclopropano steroids according to  claim 8 , namely 
 1) 3-methoxy-14α,15α-methylene-8α,9α-oxidoestra-1,3,5(10 )-trien-17α-ol,    2) 3-methoxy-14α,15α-methylene-8α,9α-oxidoestra-1,3,5(10)-trien-17α-yl acetate, 3) 3-methoxy-14α,15α-methylene-8α,9α-oxido-18α-homoestra-1,3,5(10)-trien-17α-yl propionate,    4) 14α,15α-methylene-8α,9α-oxidoestra-1,3,5(10)-trien-3,17α-diyl diacetate,    5) 3-methoxy-15α-methyl-14α,15α-methylene-8α,9α-oxidoestra-1,3,5(10)-trien-17β-ol,    6) 11α-hydroxy-3-methoxy-14α,15α-methylene-8α,9α-oxidoestra-1,3,5(10)-trien-17α-yl acetate,    7) 3-methoxy-14α,15α-methylene-8α,9α-oxidoestra-1,3,5(10)-trien-11α,17α-diydiacetate and    8) 3-methoxy-11α-hydroxy-8α,9α-oxido-14α,15α-methylenestra-1,3,5(10)-trien-17β-yl acetate.