Substituted di-arylhydantoin and di-arylthiohydantoin compounds and methods of use thereof

1. A compound of formula (I):

wherein:

W 1 is CN, NO 2 or SO 2 R 4 ;

W 2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;

Z 1 is S or O;

Z 2 is S, O or NR 4 ;

Y 1 and Y 2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, or substituted heterocyclyl; or Y 1 and Y 2 are connected to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, or substituted cycloalkyl;

T is nitrogen and can be at any position in the ring;

R 1 is —O—C 1 C 8 alkyl-NR c R d ,

where:

R c is a C 1 -C 12 alkyl and R d is H or a C 1 -C 12 alkyl; or R c and R d are taken together with the N to which they are attached to form a heterocyclic ring;

R 2 is hydrogen, halo, nitro, alkyl and substituted alkyl and

R 4 is independently H, alkyl, aryl

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, where R 2 is hydrogen.

3. The compound of claim 2 , or a pharmaceutically acceptable salt thereof, where at least one of (i)-(v) applies: (i) W 1 is CN; (ii) W 2 is perhaloalkyl; (iii) Z 1 is S; (iv) Z 2 is O; and (v) Y 1 and Y 2 are both methyl.

4. A compound of formula I:

wherein

W 1 is CN, NO 2 or SO 2 R 4 ;

W 2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;

Z 1 is S or O;

Z 2 is S, O or NR 4 ;

Y 1 and Y 2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, or substituted heterocyclyl; or Y 1 and Y 2 are connected to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, or substituted cycloalkyl;

T is nitrogen and can be at any position in the ring;

R 1 is —C 1 -C 8 alkyl-NR a R b , —O—C 1 C 8 alkyl-NR c R d or —C(O)NR e R f,

where:

R a is a C 1 -C 12 alkyl and R b is H or a C 1 -C 12 alkyl; or R a and R b are taken together with the N to which they are attached to form a heterocyclic ring;

R c is a C 1 -C 12 alkyl and R d is H or a C 1 -C 12 alkyl or R c and R d are taken together with the N to which they are attached to form a heterocyclic ring;

R e and R f are taken together with the N to which they are attached to form a heterocyclic ring;

R 2 is hydrogen, halo, nitro, alkyl and substituted alkyl and

R 4 is independently H, alkyl, aryl,

or a pharmaceutically acceptable salt thereof, wherein at least one of (i)-(v) applies; W 1 is CN; (ii) W 2 is perhaloalkyl; (iii) Z 1 is S; (iv) Z 2 is O; (v) Y 1 and Y 2 are both methyl.

5. A compound of formula (I):

wherein:

W 1 Is CN, NO 2 or SO 2 R 4 ;

W 2 is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl or halogen;

Z 1 is S or O;

Z 2 is S, O or NR 4 ;

Y 1 and Y 2 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, arylalkenyl, arylalkynyl, heteroaralkyl, heterocyclyl, or substituted heterocyclyl; or Y 1 and Y 2 are connected to form a cycle which can be heterocyclic, substituted heterocyclic, cycloalkyl, or substituted cycloalkyl;

T is carbon or nitrogen and can be at any position in the ring;

R 1 is —O—C 1 -C 8 alkyl-NR c R d ,

where:

R c is a C 1 -C 12 alkyl and R d is H or a C 1 -C 12 alkyl or R c and R d are taken together with the N to which they are attached to form a heterocyclic ring;

R 2 is hydrogen, halo, nitro, alkyl or substituted alkyl and

R 4 is H, alkyl, or aryl,

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, where R 2 is halo.

7. The compound of claim 6 , or a pharmaceutically acceptable salt thereof, where at least one of (i)-(vi) applies: (i) W 1 is CN; (ii) W 2 is perhaloalkyl; (iii) Z 1 is S; (iv) Z 2 is O; (v) Y 1 and Y 2 are both methyl and (vi) T is C.

8. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, where R 2 is hydrogen.

9. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

10. A pharmaceutical composition comprising a compound of claim 4 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

11. A pharmaceutical composition comprising a compound of claim 5 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

12. A method of treating prostate cancer in an individual in need thereof comprising administering to the individual an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

13. The method of claim 12 , where the individual has castration-resistant prostate cancer.

14. The method of claim 12 , where the individual has hormone-sensitive prostate cancer.

15. A method of treating prostate cancer in an individual in need thereof comprising administering to the individual an effective amount of a compound of claim 4 or a pharmaceutically acceptable salt thereof

16. The method of claim 15 , where the individual has castration-resistant prostate cancer.

17. The method of claim 15 , where the individual has hormone-sensitive prostate cancer.

18. A method of treating prostate cancer in an individual in need thereof comprising administering to the individual an effective amount of a compound of claim 5 or a pharmaceutically acceptable salt thereof.

19. The method of claim 18 , where the individual has castration-resistant prostate cancer.

20. The method of claim 18 , where the individual has hormone-sensitive prostate cancer.