17Afla,21-dihydroxypregnene esters as antiandrogenic agents

Abstract

17α,21-Dihydroxypregna-4,9-diene-3,20-dione and 17α,21-dihydroxypregna-4-ene-3,20-dione 17 and/or 21 esters of having remarkable antiandrogenic activity, and the processes for the preparation thereof.

1 . Compounds of formula (I)  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  and R 2 , which can be the same or different, are hydrogen or a C 3 -C 18  acyl group, with the provisos that: 
 at least one of R 1  and R 2  is different from hydrogen;  
 when R 1  is hydrogen, R 2  is different from C 3 -C 10  acyl;  
 both R 1  and R 2  cannot be propionyl.  
 
       
     
     
         2 . Compounds of formula (II)  
       
         
           
           
               
               
           
         
         wherein:  
         R 1  and R 2 , which can be the same or different, are hydrogen or a C 3 -C 18  acyl group, with the proviso that: 
 at least one of R 1  and R 2  is different from hydrogen;  
 
         as antiandrogenic drugs.  
       
     
     
         3 . A compound as claimed in  claim 2  wherein R 1  is hydrogen and R 2  is propionyl.  
     
     
         4 . A compound as claimed in  claim 2  wherein R 1  and R 2  are butanoyl.  
     
     
         5 . A process for the preparation of compounds of formula (I) or (II) in which R 1  and R 2  are both acyl groups, which process comprises reacting the corresponding compounds, wherein R 1  and R 2  are hydrogen, with carboxylic acids anhydrides or active esters in inert solvents and at temperatures ranging from −5° C. to the reaction mixture boiling temperature.  
     
     
         6 . A process for the preparation of the compounds of formula (I) or (II) in which one of R 1  or R 2  is hydrogen and the other is acyl, which process comprises: 
 a) reaction of the corresponding compounds, wherein R 1  and R 2  are hydrogen, with C 3 -C 18  carboxylic acids anhydrides or active esters or with allyloxycarbonyl chloride or isobutene in inert solvents and at temperatures ranging from −5° C. to the boiling temperature, to yield the corresponding compound in which R 1  is isobutyl, allyloxycarbonyl or C 3 -C 18  acyl;    b) optional reaction of the compound from step a) with C 3 -C 18  carboxylic acids anhydrides or active esters in inert solvents and at temperatures ranging from −5° C. to the reaction mixture boiling temperature;    c) optional lysis of the 21-allyloxycarbonyl or 21-isobutyloxy group.    
     
     
         7 . The use of the compounds of  claim 1  for the preparation of medicaments with antiandrogenic activity, in particular for the topical or systemic treatment of acne, seborrhea, hirsutism, alopecia, mastodynia, prostate hyperplasia and carcinoma, virilization syndromes in the female, early puberty, inhibition of sexual aggressiveness in the male, contraception in the male.  
     
     
         8 . Pharmaceutical compositions containing as active ingredient a compound of  claim 1  in admixture with an acceptable carrier.