Small molecules targeting androgen receptor nuclear localization and/or level in prostate cancer

Patent metadata

Field	Value
Publication number	US-9708276-B2
Application number	US-201214351126-A
Country	US
Kind code	B2
Filing date	Oct 10, 2012
Priority date	Oct 12, 2011
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

A method for treating prostate cancer in a subject, comprising administering a therapeutically effective amount of at least one agent to the subject, wherein the agent is selected from:
(a) a phenyl-substituted imidazole, or a pharmaceutically acceptable salt or ester thereof; or (b) a compound, or a pharmaceutically acceptable salt or ester thereof, having a formula I of:

wherein R 20 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro-containing group;
R 21 is an alkanediyl or a substituted alkanediyl; a is 0 or 1; c is 0 or 1; X is C or S; R 22 is a moiety that includes at least one divalent amino radical; and R 23 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro-containing group.

First claim

What is claimed is:

1. A compound, or a pharmaceutically acceptable salt or ester thereof, having a structure of formula I:

wherein R 20 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro-containing group;
R 21 is an alkanediyl or a substituted alkanediyl;
a is 0 or 1;
c is 0 or 1;
X is C or S;
R 22 is a moiety that includes at least one divalent amino radical; and
R 23 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro-containing group, with the proviso that the compound of formula I is not:

2. The compound of claim 1 , wherein c is 1.

3. The compound of claim 1 , wherein c is 0.

4. The compound of claim 2 , wherein R 20 is substituted isoxazolyl, c is 1; a is 1; R 21 is —CH 2 —, X is C, R 22 is:

and R 23 is substituted phenyl.

5. The compound of claim 2 , wherein, X is C; R 22 is:

and R 23 is substituted phenyl.

6. The compound of claim 2 , wherein R 20 is phenyl.

7. The compound of claim 2 , wherein R 22 is:

8. The compound of claim 1 , wherein R 20 is an aryl or substituted aryl; c is 1; a is 1; R 21 is —CH 2 —, X is C, R 22 is:

and R 23 is substituted phenyl.

9. The compound of claim 1 , wherein R 20 is an aryl or substituted aryl; c is 0; a is 1; R 21 is —CH 2 CH 2 —, X is C, R 22 is:

and R 23 is substituted phenyl.

10. The compound of claim 1 , wherein the compound is

11. The compound of claim 3 , wherein R 22 is:

12. The compound of claim 1 , wherein X is C.

13. The compound of claim 1 , wherein R 22 is:

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Wang Zhou
• Nelson Joel Byron
• Nguyen Minh Mindy Bao
• Lazo John S
• Johnston Paul A
• Wipf Peter

Classifications

• A61K31/407

  condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine · CPC title

• A61K31/495

  having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53}) · CPC title

• A61K31/58

  containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin (digitoxin {A61K31/7048}) · CPC title

• C07D235/02

  condensed with carbocyclic rings or ring systems · CPC title

• A61K31/496 Primary

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title