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

Abstract

The invention discloses a steroid compound having the formula (1): 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 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 - 12 . (canceled) 
   
   
       13 . a steroid compound having formula (1) 
     
       
         
         
             
             
         
       
     
     wherein:
 dotted bonds represent optional double bonds; 
 R 6  is H, ═CH 2 , —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 selected from the group consisting of fluorine atom and chlorine atom; 
 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 selected from the group consisting of fluorine atom and chlorine atom; 
 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; and 
 R E  is a β-hydroxy group. 
 
   
   
       14 . The steroid compound according to  claim 13 , wherein 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. 
   
   
       15 . A pharmaceutical composition, comprising:
 the steroid compound according to  claim 13  and a pharmaceutically acceptable auxiliary.   
   
   
       16 . A pharmaceutical composition, comprising:
 the steroid compound according to  claim 14  and a pharmaceutically acceptable auxiliary.   
   
   
       17 . A method of treating peri-menopausal or post-menopausal complaints in a patient, comprising:
 administering to the patient an effective amount of the compound according to  claim 13 .   
   
   
       18 . A method of treating peri-menopausal or post-menopausal complaints in a patient, comprising:
 administering to the patient an effective amount of the compound according to  claim 14 .   
   
   
       19 . A steroid compound having formula 3: 
     
       
         
         
             
             
         
       
       wherein R 7  is H, R 11  is H and n is 1; R 7  is CH 3 , R 11  is H and n is 1; R 7  is C 2 H 5 , R 11  is H and n is 0; or R 7  is C 2 H 5 , R 11  is H and n is 1. 
     
   
   
       20 . A pharmaceutical composition, comprising:
 the steroid compound according to  claim 19  and a pharmaceutically acceptable auxiliary.   
   
   
       21 . A method of treating peri-menopansal or post-menopausal complaints in a patient, comprising:
 administering to the patient an effective amount of the compound according to  claim 19 .