Anticancer drugs including the chemical structures of an androgen receptor ligand and a histone deacetylase inhibitor

Patent metadata

Field	Value
Publication number	US-9963433-B2
Application number	US-201715417860-A
Country	US
Kind code	B2
Filing date	Jan 27, 2017
Priority date	Jan 29, 2016
Publication date	May 8, 2018
Grant date	May 8, 2018

Abstract

A novel class of drugs for treating androgen receptor (AR) positive cancer including prostate cancer and breast cancer are described. The drugs include the chemical scaffolds of a high affinity androgen receptor ligand and a histone deacetylase inhibitor. Also described are compositions including the novel drugs and methods of treating AR positive cancer using the compositions.

First claim

What is claimed is:

1. A drug of Formula (I) or Formula (II),

wherein:
n is 1 to 10; and
R is a hydrogen atom, a halogen atom, a hydroxyl group, a nitro group, an amino group, an alkyl group, a cycloalkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an aryl group, an aralkyl group, or a heterocyclic group.

2. The drug of claim 1 , wherein R is —NHOH.

3. The drug of claim 1 , wherein the drug has Formula (II) and wherein n is 6 and R is —NHOH.

4. A pharmaceutical composition comprising the drug of claim 1 and a pharmaceutically acceptable carrier.

5. A method of providing an anti-cancer effect in a subject having androgen receptor (AR) positive cancer, wherein the method comprises administering a therapeutically effective amount of the pharmaceutical composition of claim 4 to the subject, thereby providing an anti-cancer effect in the subject.

6. The method of claim 5 , wherein the AR positive cancer is prostate cancer or breast cancer.

7. The method of claim 6 , wherein the prostate cancer is castration-resistant prostate cancer (CRPC).

8. The method of claim 5 , wherein the pharmaceutical composition further comprises an additional active ingredient.

9. The method of claim 5 , wherein the pharmaceutical composition is administered in conjunction with a second pharmaceutical composition comprising an active ingredient.

10. The method of claim 9 , wherein the pharmaceutical composition and the second pharmaceutical composition are administered simultaneously or sequentially.

11. A method of inhibiting growth of AR positive cancer cells, wherein the method comprises contacting AR positive cancer cells with an effective amount of the drug of claim 1 .

12. A method of degrading a full length androgen receptor (AR), wherein the method comprises contacting AR positive cancer cells expressing the full length AR with an effective amount of the drug of claim 1 .

Assignees

• Univ Wayne State

Inventors

• Qin Zhihui

Classifications

• C07F9/6506

  having the nitrogen atoms in positions 1 and 3 · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D233/86 Primary

  Oxygen and sulfur atoms, e.g. thiohydantoin · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• A61K31/4166

  having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin · CPC title