16, 17-carbocyclic condensed steroid compounds having slective estrogenic activity

Abstract

The invention discloses a steroid compound having the formula (1): wherein dotted bonds represent optional double bonds; R6 is H, ═CH2, or —CH3, or —CH2—CH3; R7 is H, C1-4-alkyl, C2-5 alkenyl or C2-5-alkynyl, wherein the alkyl, alkenyl or alkynyl group may be substituted with 1 to 3 halogen atoms independently chosen from the group of fluorine or chlorine atoms; R11 is H, Cl1-4-alkyl, C2-4-alkenyl, C2-4-alkynyl or C1-4-alkylidene, wherein the alkyl, alkenyl, alkynyl or alkylidene group may be substituted with 1 to 3 halogen atoms independently chosen from the group of fluorine or chlorine atoms; E represents together with carbon atoms 16 and 17 of the steroid skeleton a four to seven-membered ring, said ring being α and in cis-configuration with respect to the steroid skeleton, optionally comprising one or two endocyclic bonds; or a prodrug thereof. Such compounds can be used in therapy and for methods for selective modification of the activity of estrogen receptors.

1 . Steroid compound having the formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         dotted bonds represent optional double bonds; 
         R 6  is H, ═CH 2 , or —CH 3 , or —CH 2 —CH 3 ; 
         R 7  is H, C 1-4 -alkyl, C 2-5  alkenyl or C 2-5 -alkynyl, wherein the alkyl, alkenyl or alkynyl group may be substituted with 1 to 3 halogen atoms independently chosen from the group of fluorine or chlorine atoms; 
         R 11  is H, C 1-4 -alkyl, C 2-4 -alkenyl, C 2-4 -alkynyl or C 1-4 -alkylidene, wherein the alkyl, alkenyl, alkynyl or alkylidene group may be substituted with 1 to 3 halogen atoms independently chosen from the group of fluorine or chlorine atoms; 
         E represents together with carbon atoms 16 and 17 of the steroid skeleton a four to seven-membered ring, said ring being a in cis-configuration with respect to the steroid skeleton, optionally comprising one or two endocyclic bonds; 
         or a prodrug thereof. 
       
     
     
         2 . Steroid compound according to  claim 1 , characterised in that R 6  is H, R 7  is C 1-3 -alkyl, the E-ring is a five or six-membered ring without double bonds having a hydroxy at position 22 in S stereoconfiguration. 
     
     
         3 . Steroid compound according to  claim 1  or  2 , characterised in that the compound is according to formula 2 
       
         
           
           
               
               
           
         
         named (7α, 16β, 17α, 22S)-7-propyl-16,24-cyclo-19,21-dinorchola-1,3,5(10)-triene-3,17,22-triol, 
       
     
     
         4 . A steroid compound according to any one of  claims 1 - 3  for use in therapy. 
     
     
         5 . A method for selective modification of the activity of estrogen receptors by bringing a compound according to any one of  claim 1 - 3  into contact with estrogen receptors. 
     
     
         6 . The method according to  claim 5 , characterised in that the method is a non-medical method 
     
     
         7 . The method according to  claim 5  or  6 , characterised in that the method is a selective modification of the activity of estrogen receptors a by bringing a compound according to any one of  claims 1 - 3  into contact with estrogen receptors α. 
     
     
         8 . The method according to  claim 5  or  6 , characterised in that the method is a selective modification of the activity of estrogen receptors β by bringing a compound according to any one of  claims 1 - 3  into contact with estrogen receptors β. 
     
     
         9 . Use of the steroid compound according to any one of  claim 1 - 3  for the manufacture of a medicament for a selective estrogen receptor related treatment 
     
     
         10 . The use according to  claim 9 , characterised in that the selective estrogen receptor related treatment is the prevention or treatment of peri-menopausal or post-menopausal complaints. 
     
     
         11 . The use according to  claim 9 , characterised in that the estrogen receptor related treatment is a contraceptive treatment. 
     
     
         12 . Pharmaceutical composition comprising the steroid compound according to any one of  claims 1 - 3  and a pharmaceutically acceptable auxiliary.