Small molecule inhibitors of N-terminus activation of the androgen receptor
Compounds having a structure of Formula (A) are provided. Uses of such compounds for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are provided. Uses of compounds having a structure of Formula (F) for treatment of various indications, including prostate cancer as well as methods of treatment involving such compounds are also provided.
1. A compound of the Formula (A):
or a salt thereof, wherein:
X is C or N;
Y is O or S;
R 1 is H, OH, J, OJ, SJ, or NJJ′, wherein J and J′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic or partially aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, COOR, CONH 2 , CONHR, CONR 2 , R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is a linear, or branched saturated and unsubstituted C 1 -C 10 alkyl;
R 2 is H, an amino acid side chain or a two to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, COOR, CONH 2 , CONHR, CONR 2 , R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is a linear, or branched saturated and unsubstituted C 1 -C 10 alkyl, provided that R 2 is not a proline or phenylalanine side chain;
R 3 is H, OH, OG, SG, NGG′ or a one to ten carbon linear, branched, or non-aromatic cyclic, or aromatic or partially aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein G and G′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, COOR, CONH 2 , CONHR, CONR 2 , R, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 , wherein R is an unsubstituted C 1 -C 10 alkyl; and
R 4 and R 6 are each independently H, an amino acid side chain or a one to ten carbon linear, branched, aromatic or partially aromatic cyclic, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, OR, R, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an unsubstituted C 1 -C 10 alkyl, provided that both R 4 and R 6 are not H and provided that neither R 4 or R 6 are:
and
provided that neither R 4 or R 6 is a proline side chain;
R 5 is H, an amino acid side chain or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, CONH 2 , OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 , provided that R 5 is not a proline or phenylalanine side chain; and
is a double bond;
and provided that the compound is not:
2. A compound having the following Formula (B):
or a salt thereof, wherein:
X is C or N;
Y is O or S;
R 1 is H, OH, J, OJ, SJ, or NJJ′, wherein J and J′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ;
R 2 is H or a two to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is a linear, or branched saturated and unsubstituted C1-C10 alkyl;
R 3 is H, OH, OG, SG, NGG′ or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein G and G′ are each independently a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ; and
R 4 is H or a one to ten carbon linear, branched, aromatic cyclic, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, OR, R, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an unsubstituted C 1 -C 10 alkyl, provided that R 4 is not:
R 5 is H or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ;
Z is an optionally substituted Bu, Pr or Et, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ; and
is a single bond or a double bond,
provided that the compound is not,
3. The compound of claim 1 , wherein R 3 is H, OH, OG, or a one to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein G is a one to ten carbon linear, or branched, saturated or unsaturated alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 .
4. The compound of claim 1 , wherein R 3 is H, OH, OBu, OPr, OEt, or OMe.
5. The compound of claim 1 , wherein R 1 is H, OH, J, or OJ, wherein J is a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , and NO 2 .
6. The compound of claim 1 , wherein R 1 is H, OH, J, or OJ, wherein J is a one to four carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, and NH 2 .
7. The compound of claim 1 , wherein R 1 is H, OH, OBu, OPr, OEt, OMe, Bu, Pr, Et, or Me.
8. The compound of claim 1 , wherein R 1 is OMe.
9. The compound of claim 2 , wherein is a double bond.
10. The compound of claim 1 , wherein R 2 is H or a two to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , and NO 2 .
11. The compound of claim 1 , wherein R 2 is H or a two to four carbon linear, or branched, saturated optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, I, and NH 2 .
12. The compound of claim 1 , wherein R 4 is H or a one to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SH, SO 3 H, and NO 2 .
13. The compound of claim 1 , wherein R 4 is H or a one to four carbon linear, or branched, saturated optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, I, and NH 2 .
14. The compound of claim 1 , wherein R 5 is H or a one to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 .
15. The compound of claim 1 , wherein R 5 is H or a one to four carbon linear, or branched, saturated optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, I, and NH 2 .
16. The compound of claim 1 , wherein X is N.
17. The compound of claim 1 , wherein Y is O.
18. The compound of claim 2 , wherein Z is an optionally substituted Bu, Pr or Et, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, and I.
19. The compound of claim 2 , wherein Z is an optionally substituted Bu, Pr or Et, wherein the optional substituent is selected from one or more of: F, Cl, Br, and I.
20. The compound of claim 1 , wherein the compound has the following Formula (C):
or a salt thereof, wherein:
A is Bu, Pr, Et, or Me;
M is H, OH, OBu, OPr, OEt, OMe, Bu, Pr, Et, or Me;
T is
E is Bu, Pr, Et, or Me;
Q is
L is Bu, Pr, Et, or Me;
R 8 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me; and
R 9 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me;
and wherein,
A, T, E, Q, and L are optionally substituted, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 .
21. The compound of claim 1 , wherein the compound has the following Formula (D):
or a salt thereof, wherein:
A is Bu, Pr, Et, or Me;
D is Bu, Pr, Et, or Me;
E is Bu, Pr, Et, or Me;
L is Bu, Pr, Et, or Me;
R 8 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me; and
R 9 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me.
22. The compound of claim 1 , wherein the compound has the following Formula (E):
or a salt thereof, wherein:
R 8 is Cl 3 C, Cl 2 HC, ClH 2 C, Et, or Me; and
R 9 is Cl 3 C, Cl 2 HC, ClH 2 C, Et, or Me.
23. The compound of claim 1 , wherein the compound has one of the following structures:
24. A method for modulating androgen receptor (AR) activity, the method comprising administering to a mammalian cell a compound having a structure of Formula A:
or a salt thereof, wherein:
X is C or N;
Y is O or S;
R 1 is H, OH, J, OJ, SJ, or NJJ′, wherein J and J′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an linear, or branched saturated and unsubstituted C 1 -C 10 alkyl;
R 2 is H or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an linear, or branched saturated and unsubstituted C 1 -C 10 alkyl;
R 3 is H, OH, OG, SG, NGG′ or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein G and G′ are each independently a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ;
R 4 and R 6 are each independently H or a one to ten carbon linear, branched, aromatic cyclic, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, OR, R, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is a linear, or branched saturated and unsubstituted C 1 -C 10 alkyl;
R 5 is H or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ; and
is a single bond or a double bond.
25. A pharmaceutical composition comprising a pharmaceutically acceptable and sterile excipient and a compound having the following structure (A);
or a salt thereof, wherein;
X is C or N;
Y is O or S;
R 1 is H, OH, J, OJ, SJ, or NJJ′, wherein J and J′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic or partially aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, COOR, CONH 2 , CONHR, CONR 2 , R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an linear, or branched saturated and unsubstituted C 1 -C 10 alkyl;
R 2 is H, an amino acid side chain or a two to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, COOR, CONH 2 , CONHR, CONR 2 , R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an linear, or branched saturated and unsubstituted C 1 -C 10 alkyl, provided that R 2 is not a proline or phenylalanine side chain;
R 3 is H, OH, OG, SG, NGG′ or a one to ten carbon linear, branched, or non-aromatic cyclic, or aromatic or partially aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein G and G′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, COOR, CONH 2 , CONHR, CONR 2 , R, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 , wherein R is an unsubstituted C 1 -C 10 alkyl; and
R 4 and R 6 are each independently H, an amino acid side chain or a one to ten carbon linear, branched, aromatic or partially aromatic cyclic, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, OR, R, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an unsubstituted C 1 -C 10 alkyl, provided that both R 4 and R 6 are not H and provided that neither R 4 and R 6 are:
provided that neither R 6 or R 6 is a proline side chain;
R 5 is H, an amino acid side chain or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, CONH 2 , OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 , provided that R 5 is not a proline or phenylalanine side chain; and
is a double bond.
26. The compound of claim 2 , wherein R 3 is H, OH, OG, or a one to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein G is a one to ten carbon linear, or branched, saturated or unsaturated alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 .
27. The compound of claim 2 , wherein R 3 is H, OH, OBu, OPr, OEt, or OMe.
28. The compound of claim 2 , wherein R 1 is H, OH, J, or OJ, wherein J is a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , and NO 2 .
29. The compound of claim 2 , wherein R 1 is H, OH, J, or OJ, wherein J is a one to four carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, and NH 2 .
30. The compound of claim 2 , wherein R 1 is H, OH, OBu, OPr, OEt, OMe, Bu, Pr, Et, or Me.
31. The compound of claim 2 , wherein R 1 is OMe.
32. The compound of claim 2 , wherein R 2 is H or a two to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , and NO 2 .
33. The compound of claim 2 , wherein R 2 is H or a two to four carbon linear, or branched, saturated optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, I, and NH 2 .
34. The compound of claim 2 , wherein R 4 is H or a one to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SH, SO 3 H, and NO 2 .
35. The compound of claim 2 , wherein R 4 is H or a one to four carbon linear, or branched, saturated optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, I, and NH 2 .
36. The compound of claim 2 , wherein R 5 is H or a one to ten carbon linear, or branched, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 .
37. The compound of claim 2 , wherein R 5 is H or a one to four carbon linear, or branched, saturated optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, OH, F, Cl, Br, I, and NH 2 .
38. The compound of claim 2 , wherein X is N.
39. The compound of claim 2 , wherein Y is O.
40. A pharmaceutical composition comprising a pharmaceutically acceptable and sterile excipient and a compound having the following structure (B):
or a salt thereof, wherein:
X is C or N;
Y is O or S;
R 1 is H, OH, J, OJ, SJ, or NJJ′, wherein J and J′ are each independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ;
R 2 is H or a two to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is a linear, or branched saturated and unsubstituted C1-C10 alkyl;
R 3 is H, OH, OG, SG, NGG′ or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein G and G′ are each independently a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated alkyl group and wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ; and
R 4 is H or a one to ten carbon linear, branched, aromatic cyclic, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, OR, R, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is an unsubstituted C 1 -C 10 alkyl, provided that R 4 is not:
R 5 is H or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ;
Z is an optionally substituted Bu, Pr or Et, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ; and
is a single bond or a double bond.
41. The method of claim 25 , wherein the compound has the following Formula (B):
or a salt thereof, wherein:
X is C or N;
Y is O or S;
R 1 is H, OH, J, OJ, SJ, or NJJ′, wherein J and J′ are reach independently a one to ten carbon linear, branched, non-aromatic cyclic, or aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ;
R 2 is H or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, R, OH, OR, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , and wherein R is a linear, or branched saturated and unsubstituted C1-C10 alkyl;
R 3 is H, OH, OG, SG, NGG′ or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein G and G′ are each independently a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , CN, SH, SO 3 H, and NO 2 ;
R 4 is H or a one to ten carbon linear, branched, aromatic cyclic, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, OR, R, F, Cl, Br, I, NH 2 , NHR, NR 2 , CN, SH, SR, SO 3 H, SO 3 R, SO 2 R, OSO 3 R, and NO 2 , wherein R is an unsubstituted C 1 -C 10 alkyl,
R 5 is H or a one to ten carbon linear, branched, or non-aromatic cyclic, saturated or unsaturated, optionally substituted alkyl group, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ;
Z is an optionally substituted Bu, Pr, Et, or Me, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 ; and
is a double bond.
42. The method of claim 24 , wherein is a double bond.
43. The method of claim 24 , wherein the compound has the following Formula (C):
or a salt thereof, wherein:
A is Bu, Pr, Et, or Me;
M is H, OH, OBu, OPr, OEt, OMe, Bu, Pr, Et, or Me;
T
E is Bu, Pr, Et, or Me:
Q is
L is Bu, Pr, Et, or Me;
R 8 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me; and
R 9 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me;
and wherein,
A, T, E, Q, and L are optionally substituted, wherein the optional substituent is selected from one or more of: oxo, COOH, OH, F, Cl, Br, I, NH 2 , SO 3 H, and NO 2 .
44. The method of claim 24 , wherein the compound has the following Formula (D):
or a salt thereof, wherein:
A is Bu, Pr, Et, or Me;
D is Bu, Pr, Et, or Me;
E is Bu, Pr, Et, or Me;
L is Bu, Pr, Et, or Me;
R 8 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me; and
R 9 is Cl 3 C, Cl 2 HC, ClH 2 C, Bu, Pr, Et, or Me.
45. The method of claim 24 , wherein the compound has the following Formula (E):
or a salt thereof, wherein:
R 8 is Cl 3 C, Cl 2 HC, ClH 2 C, Et, or Me; and
R 9 is Cl 3 C, Cl 2 HC, ClH 2 C, Et, or Me.
46. The method of claim 24 , wherein the compound has one of the following structures:
47. The method of claim 24 , wherein the modulation of AR activity is in a human cell.
48. The method of claim 24 , wherein the modulation of AR activity is for the inhibition of AR N-terminal domain (NTD) activity.
49. The method of claim 24 , wherein the modulation of AR activity is for the prevention or treatment of prostate cancer, breast cancer, ovarian cancer, endometrial cancer, hair loss, acne, hirsutism, ovarian cysts, polycystic ovary disease, precocious puberty, or age-related macular degeneration.
50. The method of claim 49 , wherein the modulation of AR activity is for the prevention or treatment of prostate cancer.
51. The method of claim 50 , wherein the prostate cancer is androgen-independent prostate cancer.
52. The method of claim 50 , wherein the prostate cancer is androgen-dependent prostate cancer.
53. The pharmaceutical composition of claim 25 , wherein the compound is not:
54. The pharmaceutical composition of claim 40 , wherein the compound is not: