Substituted (e)-n'-(1-phenylethylidene)benzohydrazide analogs as histone demethylase inhibitors

Patent metadata

Field	Value
Publication number	US-2016120875-A1
Application number	US-201614987460-A
Country	US
Kind code	A1
Filing date	Jan 4, 2016
Priority date	Aug 15, 2011
Publication date	May 5, 2016
Grant date	—

Abstract

Methods of treatment of disorders of uncontrolled cellular proliferation, including cancer, by administering substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs, derivatives thereof, and related compounds to mammals in need thereof.

First claim

What is claimed is:

1 . A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound having a structure represented by a formula (I)

wherein
m is 1;
n is an integer from 0;
X is selected from the group consisting of OH, NO 2 and F;
Z is selected from the group consisting of N and CH;
R 1 is selected from the group consisting of halo, C1-C3 haloalkyl, and C1-C3 polyhaloalkyl,
each of R 2 , R 3 , and R 4 is independently selected from the group consisting of hydrogen, hydroxyl, cyano, amino, C2-C6 alkalkoxy, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 polyhaloalkyl, and C1-C6 haloalkyl;
R 5 is selected from the group consisting of NR 6 R 7 , C1-C6 alkyl, C3-C6 cycloalkyl,

 and Cy, and substituted with 0-3 groups independently selected from halo, hydroxyl, amino, C2-C6 alkalkoxy, C1-C6 alkylalcohol, C1-C6 alkoxy, C1-C6 alkyl, C1-C6 polyhaloalkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, and Cy;
Cy is a heterocycloalkyl selected from the group consisting of aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, oxazolidinyl, imidazolidinyl, pyrazolidinyl, piperazinyl, oxazinanyl, morpholinyl, hexahydrophyrimidinyl, and hexahydropyridazinyl; and
each of R 6 and R 7 is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, and C3-C6 heterocycloalkyl;
or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein said disorder of uncontrolled cellular proliferation is associated with a histone demethylase dysfunction.

3 . The method of claim 1 , wherein said disorder of uncontrolled cellular proliferation is cancer.

4 . The method of claim 3 , wherein said cancer is a sarcoma.

5 . The method of claim 3 , wherein said cancer is a prostate cancer.

6 . The method of claim 3 , wherein said cancer is a breast cancer.

7 . The method of claim 1 , wherein said mammal is a human.

8 . A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

9 . The method of claim 8 , wherein said disorder of uncontrolled cellular proliferation is cancer.

10 . The method of claim 9 , wherein said cancer is a sarcoma.

11 . The method of claim 9 , wherein said cancer is a prostate cancer.

12 . The method of claim 9 , wherein said cancer is a breast cancer.

13 . The method of claim 8 , wherein said mammal is a human.

14 . A method for the treatment of a disorder of uncontrolled cellular proliferation in a mammal, the method comprising the step of administering to the mammal an effective amount of a compound having a structure represented by a formula:

or a pharmaceutically acceptable salt thereof.

15 . The method of claim 14 , wherein said disorder of uncontrolled cellular proliferation is associated with a histone demethylase dysfunction.

16 . The method of claim 14 , wherein said disorder of uncontrolled cellular proliferation is cancer.

17 . The method of claim 16 , wherein said cancer is a sarcoma.

18 . The method of claim 16 , wherein said cancer is a prostate cancer.

19 . The method of claim 16 , wherein said cancer is a breast cancer.

20 . The method of claim 14 , wherein said mammal is a human.

Assignees

• Univ Utah Res Found

Inventors

• Vankayalapati Hariprasad
• Sorna Venkataswamy
• Warner Steven L
• Stephens Bret
• Bearss David J
• Sharma Sunil

Classifications

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• C07D213/71

  to which a second hetero atom is attached · CPC title

• C07D231/12

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D207/48

  Sulfur atoms · CPC title

• A61K31/4453

  only substituted in position 1, e.g. propipocaine, diperodon · CPC title