16alpha-methyl or ethyl substituted estrogens

Abstract

The invention makes a 16α-substituted steroidal compound available having formula 1, wherein the dotted ring is a fully saturated, a fully aromatic or a saturated ring with a Δ5-10 double bond; R 1 is (C 1 -C 3 )alkyl or (C 2 -C 3 )alkenyl, and each of these groups can be substituted with one or more halogens; R 2 is (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl or methylene, and each of these groups can be substituted with one or more halogens; R 3 is methyl or ethyl; or a prodrug thereof, which compound can be used for an estrogen receptor α selective treatment.

1 - 9 . (canceled) 
   
   
       10 . A method of hormone replacement therapy or contraception, the method comprising administering to a female an effective amount of a 16α-substituted steroidal compound having formula I, 
     
       
         
         
             
             
         
       
       wherein: 
       the dotted ring is a fully aromatic or a saturated ring with a Δ5-10 double bond; 
       R 1  is (C 1 -C 3 )alkyl or (C 2 -C 3 )alkenyl, and each of these groups can be substituted with one or more halogens; 
       R 2  is (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl or methylene, and each of these groups can be substituted with one or more halogens; 
       R 3  is methyl or ethyl. 
     
   
   
       11 . The method according to  claim 10 , wherein in the 16α-substituted steroidal compound of Formula I, the halogens in R 1  and R 2  are selected from a group consisting of chlorine and fluorine. 
   
   
       12 . The method according to  claim 10 , wherein in the 16α-substituted steroidal compound of Formula I, R 2  is (C 1 -C 2 )alkyl or vinyl. 
   
   
       13 . A method for treating osteoporosis or Alzheimer's disease, the method comprising administering to a patient an effective amount of a 16α-substituted steroidal compound having formula I, 
     
       
         
         
             
             
         
       
       wherein: 
       the dotted ring is a fully aromatic or a saturated ring with a Δ5-10 double bond; 
       R 1  is (C 1 -C 3 )alkyl or (C 2 -C 3 )alkenyl, and each of these groups can be substituted with one or more halogens; 
       R 2  is (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl or methylene, and each of these groups can be substituted with one or more halogens; 
       R 3  is methyl or ethyl. 
     
   
   
       16 . The method according to claim  15 , wherein in the 16α-substituted steroidal compound of Formula I, the halogens in R 1  and R 2  are selected from a group consisting of chlorine and fluorine. 
   
   
       17 . The method according to claim  15 , wherein in the 16α-substituted steroidal compound of Formula I, R 2  is (C 1 -C 2 )alkyl or vinyl.