SMALL MOLECULE INHIBITORS OF THE NUCLEAR TRANSLOCATION OF ANDROGEN RECEPTOR FOR THE TREATMENT OF CASTRATION-RESISTANT PROSTATE CANCER
A compound, or a pharmaceutically acceptable salt or ester thereof, according to formula I: R 20 —(Z) b —(Y) c —(R 21 ) a —(X) d —R 22 —R 23 wherein R 20 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, S(═O), —S(═O)(═O)—, or NR 10 , wherein R 10 is H or alkyl; R 21 is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl alkadienyl, substituted alkadienyl, alkatrienyl, substituted alkatrienyl; X is —C(═O)—, —S(═O)(═O)—, or —N(H)C(═O)—; R 22 includes at least one divalent amino radical; R 23 is aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a thio-containing group, or a seleno-containing group; a, b, c, and d independently are 0 or 1.
1 . A compound, or a pharmaceutically acceptable salt or ester thereof, selected from:
2 . The compound of claim 1 , wherein the compound is:
3 . The compound of claim 1 , wherein the compound is:
4 . The compound of claim 1 , wherein the compound is:
5 . A pharmaceutical composition comprising at least one pharmaceutically acceptable additive, and a compound of claim 1 .
6 . The pharmaceutical composition of claim 5 , wherein the compound is:
7 . The pharmaceutical composition of claim 5 , wherein the compound is:
8 . The pharmaceutical composition of claim 5 , wherein the compound is:
9 . A method for treating prostate cancer in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 .
10 . The method of claim 9 , wherein the prostate cancer is castration-resistant prostate cancer.
11 . The method of claim 9 , wherein the compound is orally administered.
12 . The method of claim 9 , wherein the method is used in combination with androgen deprivation therapy.
13 . The method of claim 9 , wherein the agent is co-administered with abiratrone.
14 . The method of claim 9 , wherein the agent is co-administered with enzalutamide.
15 . The method of claim 9 , wherein the method further comprises identifying a subject that is in need of treatment with the agent.
16 . The method of claim 9 , wherein the compound is:
17 . The method of claim 9 , wherein the compound is:
18 . The method of claim 9 , wherein the compound is: