Novel androgens

Abstract

The compounds of the subject invention have a structure according to formula I: wherein X is S or SO 2 ; R 1 is (1C-6C)alkyl, (3C-6C)alkenyl, or (3C-6C)alkynyl, each optionally substituted with (3C-6C)cycloalkyl, OH, OC(O)(1C-4C)alkyl, (1C-4C)alkoxy, halogen, cyano, formyl, C(O)(1C-4C)alkyl, CO 2 H, CO 2 (1C-4C)alkyl, C(O)NR 5 R 6 , S(O)(1C-4C)alkyl or S(O) 2 (1C-4C)alkyl; R 2 is hydrogen, (1C-4C)alkyl or C(O)(1C-4C)alkyl; R 3 is a phenyl group optionally substituted with (1C-4C)alkyl, (1C-4C)fluoroalkyl, (1C-4C)alkoxy, (1C-4C)fluoroalkoxy, halogen, cyano or nitro; or R 3 is a 5- or 6-membered aromatic heterocyclic ring structure optionally substituted with (1C-4C)alkyl, (1C-4C)fluoroalkyl, (1C-4C)alkoxy, halogen or cyano; R 4 is a phenyl group or an aromatic 6-membered heterocycle, substituted at the ortho position with 1-hydroxy(1C-4C)alkyl, (1C-4C)alkoxy, C(O)(1C-4C)alkyl, CO 2 (1C-4C)alkyl, C(O)NH 2 , cyano, nitro, or CH═NOR 7 , and optionally further substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen; or R 4 is 2-pyridyl optionally substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen; R 5 and R 6 are independently hydrogen or (1C-4C)alkyl; R 7 is hydrogen or C(O)(1C-4C)alkyl; R 8 , R 9 , R 10 are independently hydrogen, (1C-2C)alkyl, fluoro or chloro; or a salt or hydrate form thereof.

1 . A compound of formula I: 
       
         
           
           
               
               
           
         
       
       wherein
 X is S or SO 2 ; 
 R 1  is (1C-6C)alkyl, (3C-6C)alkenyl, or (3C-6C)alkynyl, each optionally substituted with (3C-6C)cycloalkyl, OH, OC(O)(1C-4C)alkyl, (1C-4C)alkoxy, halogen, cyano, formyl, C(O)(1C-4C)alkyl, CO 2 H, CO 2 (1C-4C)alkyl, C(O)NR 5 R 6 , S(O)(1C-4C)alkyl or S(O) 2 (1C-4C)alkyl; 
 R 2  is hydrogen, (1C-4C)alkyl or C(O)(1C-4C)alkyl; 
 R 3  is a phenyl group optionally substituted with (1C-4C)alkyl, (1C-4C)fluoroalkyl, (1C-4C)alkoxy, (1C-4C)fluoroalkoxy, halogen, cyano or nitro; 
 R 4  is a phenyl group or an aromatic 6-membered heterocycle, substituted at the ortho position with 1-hydroxy(1C-4C)alkyl, (1C-4C)alkoxy, C(O)(1C-4C)alkyl, CO 2 (1C-4C)alkyl, C(O)NH 2 , cyano, nitro, or CH═NOR 7 , and optionally further substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen; 
 R 5  and R 6  are independently hydrogen or (1C-4C)alkyl; 
 R 7  is hydrogen or C(O)(1C-4C)alkyl; and 
 R 8 , R 9 , R 10  are independently hydrogen, (1C-2C)alkyl, fluoro or chloro; 
 or a salt thereof. 
 
     
     
         2 . A compound according to  claim 1 , wherein R 8 , R 9 , R 10  are hydrogen. 
     
     
         3 . A compound according to  claim 2 , wherein
 R 2  is hydrogen, (1C-2C)alkyl or C(O)CH 3 ;   R 3  is a phenyl group optionally substituted at the 3-, 4- or 5-position with (1C-2C)alkyl, (1C-2C)fluoroalkyl, (1C-2C)alkoxy, (1C-2C)fluoroalkoxy, halogen, cyano or nitro;   R 4  is a phenyl group, substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOR 7 , and optionally further substituted with (1C-2C)alkyl, (1C-2C)fluoroalkyl or halogen;   R 7  is hydrogen or C(O)(1C-2C)alkyl.   
     
     
         4 . A compound according to  claim 3 , wherein
 X is S;   R 1  is (1C-4C)alkyl, (3C-6C)alkenyl, or (3C-6C)alkynyl, each optionally substituted with (3C-6C)cycloalkyl, OH, OC(O)(1C-2C)alkyl, (1C-2C)alkoxy, halogen, cyano, formyl, C(O)(1C-2C)alkyl, CO 2 H or CO 2 (1C-2C)alkyl;   R 3  is a phenyl group optionally substituted at the 3-, 4- or 5-position with methyl, CF 3 , methoxy, OCF 3 , fluoro, chloro, cyano or nitro; and   R 4  is a phenyl group or an aromatic 6-membered heterocycle, substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOH.   
     
     
         5 . A compound according to  claim 4 , wherein R 2  is hydrogen. 
     
     
         6 . A compound according to  claim 5 , wherein
 R 3  is a phenyl group optionally substituted at the 3-, 4- or 5-position with methyl, CF 3 , methoxy, OCF 3 , fluoro, chloro, cyano or nitro.   
     
     
         7 . A compound according to  claim 6 , wherein
 R 4  is a phenyl group substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOH.   
     
     
         8 . A compound according to  claim 7 , wherein
 R 1  is (1C-4C)alkyl optionally substituted with OH, (1C-2C)alkoxy, cyano, C(O)(1C-2C)alkyl or CO 2 (1C-2C)alkyl;   R 3  is a phenyl group, optionally substituted at the 3-, 4- or 5-position with fluoro or chloro; and   R 4  is a phenyl group, substituted at the ortho position with hydroxymethyl, cyano or nitro.   
     
     
         9 . A compound according to  claim 8 , wherein
 R 1  is (1C-4C)alkyl optionally substituted with OH, methoxy, cyano, C(O)CH 3  or CO 2 CH 3 ; and R 4  is a 2-nitrophenyl group.   
     
     
         10 . A compound according to  claim 9  selected from the group consisting of
 [1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-yl]-methyl-amine; 
 [1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamino]-acetonitrile; 
 1-[1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamino]-propan-2-one; 
 2-[1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-ylamino]-ethanol; and 
 [1-(3,5-difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indol-6-yl]-(2-methoxy-ethyl)-amine. 
 
     
     
         11 . A compound according to  claim 8 , wherein
 R 1  is (1C-4C)alkyl optionally substituted with OH, methoxy, cyano, C(O)CH 3  or CO 2 CH 3 ; and   R 4  is a 2-cyanophenyl group.   
     
     
         12 . The compound according to  claim 11  which is 2-[1-(3,5-difluoro-benzyl)-6-methylamino-1H-indol-3-ylsulfanyl]-benzonitrile. 
     
     
         13 . (canceled) 
     
     
         14 . A compound according to  claim 13 , wherein
 R 4  is a phenyl group substituted at the ortho position with hydroxymethyl, methoxy, C(O)CH 3 , CO 2 CH 3 , C(O)NH 2 , cyano, nitro or CH═NOH.   
     
     
         15 - 22 . (canceled) 
     
     
         23 . A pharmaceutical composition comprising a compound according to  claim 1  or a salt thereof and a pharmaceutically acceptable carrier. 
     
     
         24 - 33 . (canceled) 
     
     
         34 . A method of treating osteoporosis comprising administering a pharmaceutically effective amount of a compound according to  claim 1  or a salt thereof to a subject in need thereof.