Substituted androst-4-ene diones

Abstract

The disclosure relates to novel C4 and C6 substituted androst-4-ene diones as well as andros-1,4-diene diones and derivatives thereof, their process of preparation, pharmaceutical compounds containing them, and the use of said compounds for the treatment of hormone-related disorders in mammals. This includes hormone-dependent cancers, particularly those caused by elevated levels of estrogen and its intermediates. These compounds can also be used in the treatment of other hormone-related disorders, including benign prostatic hyperplasia, cardiovascular disease, and neurodegenerative disorders.

What we claim: 
     
         1 . A method of treating a hormone-related disorders comprising administering a compound of Formula C 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof or a pharmaceutically acceptable ester thereof, wherein 
         ----- represents a bond present as a double bond and 
         R 2  is selected from the group consisting of an alkenyl group and an alkynyl group, either of which may be optionally substituted, to a subject in need thereof. 
       
     
     
         2 . The method of  claim 1 , wherein the substituent is selected from OH, phenyl, benzyl, naphthyl, substituted aryl, or C 1  to C 8  alkyl group. 
     
     
         3 . The method of  claim 1 , wherein the substituent is selected from aryl, substituted aryl, heterocyclo, substituted heterocyclo, carbocyclo, substituted carbocyclo, or halo. 
     
     
         4 . The method of  claim 1 , wherein the substituent is selected from alkoxy, aryloxy, alkylester, arylester, alkanoyl or aryoyl, any of which may be optionally substituted. 
     
     
         5 . The method of  claim 1 , wherein the compound is selected from the list:
 (6R,8R,9S,10R,13 S,14S)-10,13-dimethyl-6-((E)-pent-2-en-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;   (6R,8R,9S,10R,13 S,14S)-10,13-dimethyl-6-((Z)-pent-2-en-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;   (6R,8R,9S,10R,13 S,14S)-6-(cinnamyloxy)-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;   (6R,8R,9S,10R,13 S,14S)-10,13-dimethyl-6-(3-phenylpropoxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;   (6R,8R,9S,10R,13 S,14S)-10,13-dimethyl-6-((5-phenylpentyl)oxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione;   (6R,8R,9S,10R,13 S,14S)-10,13-dimethyl-6-(oct-2-yn-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione; and   (6R,8R,9S,10R,13 S,14S)-10,13-dimethyl-6-(pent-2-yn-1-yloxy)-7,8,9,10,11,12,13,14,15,16-decahydro-3H-cyclopenta[a]phenanthrene-3,17(6H)-dione.   
     
     
         6 . The method of  claim 1 , wherein the subject is diagnosed with, at risk of, or exhibiting symptoms of a hormone-related disorder. 
     
     
         7 . The method of  claim 1 , wherein the hormone related disorder is osteoporosis, endometriosis, breast cancer, benign breast cancer, uterine cancer, ovarian cancer, polycystic ovarian disease, prostate cancer, or benign prostatic hyperplasia (BPH). 
     
     
         8 . The method of  claim 1 , wherein the pharmaceutical composition is administered in combination with estrogen.