17β-hydroxysteroid dehydrogenase type 3 inhibitors for the treatment of androgen dependent diseases
View Patent ↗In its many embodiments, the present invention provides a novel class of compounds as inhibitors of type 3 17 β-hydroxysteroid dehydrogenase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with type 3 17 β-hydroxysteroid dehydrogenase using such compounds or pharmaceutical compositions. In one embodiment, the present invention discloses a compound having the general structure shown in Formula I: wherein the various moieties are as defined herein.
1. A compound represented by the structural formula:
wherein:
X is N;
Z is O or N(R 6 );
R 1 and R 2 are the same or different, each being independently selected from the group consisting of aryl, and aralkyl, wherein each of said aryl, and aralkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, aralkyl, cycloalkyl, CF 3 , CN, —OCF 3 , —OR 6 , —C(O)R 7 , —NR 6 R 7 , —C(O)OR 6 , —C(O)NR 6 R 7 , —SR 6 , —S(O 2 )R 7 , —S(O 2 )NR 6 R 7 , —N(R 6 )S(O 2 )R 7 , —N(R 6 )C(O)R 7 and —N(R 6 )C(O)NR 6 R 7 ;
R 3 is H or —OR 6 , with the proviso that when X is N, R 3 is not —OR 6 ;
R 4 is selected from the group consisting of H, alkyl, aryl, cycloalkyl, aralkyl, and aralkyl;
m is a number from 0 to 4, and when m is more than 1, the R 4 groups can be the same or different and are independently selected;
R 5 is —C(O)R 7 or —S(O 2 )R 7 ;
R 6 is selected from the group consisting of H, alkyl, aryl, aralkyl, and cycloalkyl, wherein each of said alkyl, aryl, aralkyl, and cycloalkyl can be unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF 3 , OCF 3 , CN, —OR 7 , —NHR 7 , —N(R 7 ) 2 , —CH 2 OR 7 , —C(O)R 7 , —C(O)OR 7 , —C(O)NHR 7 , —C(O)N(R 7 ) 2 , —SR 7 , —S(O 2 )R 7 , —S(O 2 )NHR 7 , —S(O 2 )N(R 7 ) 2 , —N(R 7 )S(O 2 )R 7 , —N(R 7 )C(O)R 7 , —N(R 7 )C(O)NHR 7 and —N(R 7 )C(O)N(R 7 ) 2 ; and
R 7 is selected from the group consisting of alkyl, aryl, aralkyl, —OR 6 , —NHR 6 , and —N(R 6 ) 2 , wherein each of said alkyl, aryl, and aralkyl can be unsubstituted or optionally substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, aryl, cycloalkyl, CF 3 , OCF 3 , CN, —OR 6 , —NHR 6 , —N(R 6 ) 2 , —CH 2 OR 6 , —C(O)OR 6 , —C(O)NHR 6 , —C(O)N(R 6 ) 2 , —SR 6 , —S(O 2 )R 6 , —S(O 2 )NHR 6 , —S(O 2 )N(R 6 ) 2 , —N(R 6 )S(O 2 )R 6 , —N(R 6 )C(O)R 6 , —N(R 7 )C(O)NHR 6 and —N(R 7 )C(O)N(R 7 ) 2 , further wherein the two R 6 or the two R 7 groups in the moieties —N(R 6 ) 2 and —N(R 7 ) 2 respectively can be the same or different and are independently selected, and still further wherein any two adjacent alkyl substituents on an aryl can be joined together to form a methylenedioxy or ethylenedioxygroup.
2. The compound of claim 1 , wherein Z is O.
3. The compound of claim 1 , wherein Z is N(R 6 ).
4. The compound of claim 1 , wherein R 1 and R 2 are the same and are aryl, wherein said aryl is either unsubstituted or optionally independently substituted with one or more moieties which can be the same or different, each moiety being independently selected from the group consisting of halogen, alkyl, —CF 3 , —CN, —OCF 3 , —OR 6 , —C(O)R 7 , and —C(O)OR 6 .
5. The compound of claim 1 , wherein R 3 is H.
6. The compound of claim 1 , wherein R 4 is H.
7. The compound of claim 1 , wherein R 5 is —C(O)R 7 or —S(O 2 )R 7 .
8. The compound of claim 7 , wherein R5 is —C(O)R 7 .
9. The compound of claim 1 , wherein R 6 is selected from the group consisting of H, alkyl, aryl, —CF 3 , —C(O)R 7 and —S(O 2 )R 7 .
10. The compound of claim 9 , wherein R 6 is H, methyl or CF 3 .
11. The compound of claim 1 , wherein R 7 is selected from the group consisting of alkyl, aralkyl and aryl.
12. The compound of claim 3 , wherein R 6 is H.
13. The compound of claim 4 , wherein R 1 and R 2 are the same and are phenyl, wherein said both phenyl groups are unsubstituted.
14. The compound of claim 4 , wherein R 1 is unsubstituted phenyl and R 2 is a phenyl substituted with one or more moieties selected from the group consisting of halogen, alkyl, —CF 3 , —OCF 3 , and —C(O)R 7 .
15. The compound of claim 11 , wherein R 7 is alkyl.
16. A compound of the formula:
or stereoisomer thereof, or a pharmaceutically acceptable salt or solvate of said compound or of said stereoisomer.
17. A compound having the structure:
or a pharmaceutically acceptable salt or solvate thereof.
18. A compound having the structure:
or a pharmaceutically acceptable salt or solvate thereof.
19. A compound having the structure:
or a pharmaceutically acceptable salt or solvate thereof.
20. A compound having the structure:
or a pharmaceutically acceptable salt or solvate thereof.
21. A pharmaceutical composition comprising a therapeutically effective amount of at least one compound of claim 1 in combination with at least one pharmaceutically acceptable carrier.