Androgen receptor-ablative agents

1. A compound having the structure

2. A compound selected from the group consisting of:

a. 5-[3-Bromo-4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione

b. 5-[4-(1-Methyl-cyclohexylmethoxy)-3-nitro-benzylidene]-thiazolidine-2,4-dione

c. 5-[4-(1-Methyl-cyclohexylmethoxy)-3-trifluoromethyl-benzylidene]-thiazolidine-2,4-dione

d. 5-[3-Methoxy-4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione

e. 5-[3-Ethoxy-4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione

f. 5-[3,5-Dimethyl-4-(1-methyl-cyclohexylmethoxy)-benzylidene]-thiazolidine-2,4-dione

and

g. 5-[4-(1-Methyl-cyclohexylmethoxy)-naphthalen-1-ylmethylene]-thiazolidine-2,4-dione

3. A compound of Formula IV:

wherein R 2 is selected from the group consisting of hydrogen, halo, amino, methoxy, ethoxy, nitro, phenyl, di-alkyl, di-halo, trifluoromethyl, and hydroxyl.

4. A compound of claim 3 , wherein the compound is selected from the group consisting of:

a. 5-(4-Hydroxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

b. 5-(4-Hydroxy-3-trifluoromethyl-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

c. 5-(4-Hydroxy-3-nitro-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

d. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

e. 5-(4-Hydroxy-3-methoxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

f. 5-(3,5-Dibromo-4-hydroxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

g. 5-(4-Hydroxy-3-iodo-5-methoxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

h. 5-(4-Hydroxy-3,5-dimethyl-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

and

i. 5-(4-Hydroxy-naphthalen-1-ylmethylene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

5. A compound of Formula V:

wherein R 3 is selected from the group consisting of hydrogen, alkyl, cyclic alkyl, and arylmethoxy.

6. The compounds of claim 5 , wherein the compounds are selected from the group consisting of:

a. 5-(3-Bromo-4-hydroxy-benzylidene)-3-ethyl-thiazolidine-2,4-dione

b. 5-(3-Bromo-4-hydroxy-benzylidene)-3-propyl-thiazolidine-2,4-dione

c. 5-(3-Bromo-4-hydroxy-benzylidene)-3-butyl-thiazolidine-2,4-dione

d. 5-(3-Bromo-4-hydroxy-benzylidene)-3-pentyl-thiazolidine-2,4-dione

e. 5-(3-Bromo-4-hydroxy-benzylidene)-3-isopropyl-thiazolidine-2,4-dione

f. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(4-methyl-pentyl)-thiazolidine-2,4-dione

g. 5-(3-Bromo-4-hydroxy-benzylidene)-3-cyclohexylmethyl-thiazolidine-2,4-dione

h. 3-Allyl-5-(3-bromo-4-hydroxy-benzylidene)-thiazolidine-2,4-dione

i. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(3-methyl-but-2-enyl)-thiazolidine-2,4-dione

j. 3-Benzyl-5-(3-bromo-4-hydroxy-benzylidene)-thiazolidine-2,4-dione

k. 4-[5-(3-Bromo-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl]-benzonitrile

l. 4-[5-(3-Bromo-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-butyronitrile

m. 4-[5-(3-Bromo-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-butyric acid ethyl ester

n. 6-[5-(3-Bromo-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-2,2-dimethyl-hexanenitrile

o. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(tetrahydro-pyran-2-ylmethyl)-thiazolidine-2,4-dione

p. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(6,6-dimethyl-[1,3]dioxan-4-ylmethyl)-thiazolidine-2,4-dione

q. 5-(3-Bromo-4-hydroxy-benzylidene)-3-naphthalen-1-ylmethyl-thiazolidine-2,4-dione

r. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(3-chloro-5-fluoro-benzyl)-thiazolidine-2,4-dione

s. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-thiazolidine-2,4-dione

t. 3-(4-Benzoyl-benzyl)-5-(3-bromo-4-hydroxy-benzylidene)-thiazolidine-2,4-dione

u. 4′-[5-(3-Bromo-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl]-biphenyl-2-carbonitrile

7. A compound of Formula VI:

wherein R 3 is selected from the group consisting of hydrogen, alkyl, cyclic alkyl, and arylmethoxy.

8. The compounds of claim 7 , wherein the compounds are selected from the group consisting of:

a. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-ethyl-thiazolidine-2,4-dione

b. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-propyl-thiazolidine-2,4-dione

c. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-butyl-thiazolidine-2,4-dione

d. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-pentyl-thiazolidine-2,4-dione

e. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-isopropyl-thiazolidine-2,4-dione

f. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-(4-methyl-pentyl)-thiazolidine-2,4-dione

g. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-cyclohexylmethyl-thiazolidine-2,4-dione

h. 3-Allyl-5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-thiazolidine-2,4-dione

i. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-(3-methyl-but-2-enyl)-thiazolidine-2,4-dione

j. 3-Benzyl-5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-thiazolidine-2,4-dione

k. 4-[5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl]-benzonitrile

l. 4-[5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-butyronitrile

m. 4-[5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-butyric acid ethyl ester

n. 6-[5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-yl]-2,2-dimethyl-hexanenitrile

o. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-(tetrahydro-pyran-2-ylmethyl)-thiazolidine-2,4-dione

p. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-(6,6-dimethyl-[1,3]dioxan-4-ylmethyl)-thiazolidine-2,4-dione

q. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-naphthalen-1-ylmethyl-thiazolidine-2,4-dione

r. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-(3-chloro-5-fluoro-benzyl)-thiazolidine-2,4-dione

s. 5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-3-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-thiazolidine-2,4-dione

t. 3-(4-Benzoyl-benzyl)-5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-thiazolidine-2,4-dione

u. 4′-[5-(3-Trifluoromethyl-4-hydroxy-benzylidene)-2,4-dioxo-thiazolidin-3-ylmethyl]-biphenyl-2-carbonitrile

9. A compound selected from the group consisting of:

a. 5-(4-Fluoro-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

b. 5-(4-Chloro-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

c. 5-(4-Bromo-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

d. 3-(1-Methyl-cyclohexylmethyl)-5-(4-nitro-benzylidene)-thiazolidine-2,4-dione

e. 3-(1-Methyl-cyclohexylmethyl)-5-(4-trifluoromethoxy-benzylidene)-thiazolidine-2,4-dione

f. 5-(4-Diethylamino-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

g. 5-(4-Dimethylamino-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

h. 5-(4-Hydroxymethyl-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

i. 4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-benzonitrile

j. 4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-benzaldehyde

k. 4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-benzoic acid methyl ester

l. 4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-benzoic acid

m. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-acetamide

n. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-propionamide

o. Hexadecanoic acid {4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-amide

p. Cyclohexanecarboxylic acid {4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-amide

q. 2,2,2-Trichloro-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-acetamide

r. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-benzamide

s. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-methanesulfonamide

t. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-2-nitro-benzenesulfonamide

u. N-(4-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenylsulfamoyl}-phenyl)-acetamide

v. 4-Methyl-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-benzenesulfonamide

w. 4-Chloro-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-benzenesulfonamide

x. 4-(Z)-Acetyl-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-benzenesulfonamide

y. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-4-nitro-benzenesulfonamide

z. N-{4-[3-(1-Methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-4-nitro-3-trifluoromethyl-benzenesulfonamide

aa. 4-Chloro-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-3-nitro-benzenesulfonamide

ab. 2-Methoxy-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-4-nitro-benzenesulfonamide

ac. 3,4-Dimethoxy-N-{4-[3-(1-methyl-cyclohexylmethyl)-2,4-dioxo-thiazolidin-5-ylidenemethyl]-phenyl}-benzenesulfonamide

10. A method of treating, inhibiting, or delaying the onset of prostate cancer in a subject in need of treatment, the method comprising administering a therapeutically effective amount of a compound of Formula I:

wherein R 1 is selected from the group consisting of hydroxyl, amino, halo, hydroxyalkyl, alkylmethoxy, cycloalkylmethoxy, arylmethoxy, NHCOR, NHSO 2 R, and CH 2 R;

wherein R 2 is selected from the group consisting of hydrogen, halo, amino, methoxy, ethoxy, nitro, phenyl, di-alkyl, di-halo, trifluoromethyl, and hydroxyl;

wherein R 3 is selected from the group consisting of hydrogen, alkyl, cyclic alkyl, and arylmethoxy;

or a pharmaceutically-acceptable salt thereof, to the subject in need of such treatment.

11. The method of claim 10 , wherein the prostate cancer is hormone-refractory prostate cancer (HRPC).

12. The method of claim 10 , wherein R 1 is a hydroxyl moiety and R 3 is a 1-methyl-cyclohexylmethyl moiety.

13. The method of claim 12 , wherein the compound is selected from the group consisting of:

a. 5-(4-Hydroxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

b. 5-(4-Hydroxy-3-trifluoromethyl-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

c. 5-(4-Hydroxy-3-nitro-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

d. 5-(3-Bromo-4-hydroxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

e. 5-(4-Hydroxy-3-methoxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

f. 5-(3,5-Dibromo-4-hydroxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

g. 5-(4-Hydroxy-3-iodo-5-methoxy-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

h. 5-(4-Hydroxy-3,5-dimethyl-benzylidene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione

i. 5-(4-Hydroxy-naphthalen-1-ylmethylene)-3-(1-methyl-cyclohexylmethyl)-thiazolidine-2,4-dione