Substituted (E)-N′-(1-phenylethylidene)benzohydrazide analogs as histone demethylase inhibitors

Patent metadata

Field	Value
Publication number	US-9642857-B2
Application number	US-201614987460-A
Country	US
Kind code	B2
Filing date	Jan 4, 2016
Priority date	Aug 15, 2011
Publication date	May 9, 2017
Grant date	May 9, 2017

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 cancer in a mammal, wherein the cancer is selected from the group consisting of uterine cancer, prostate cancer, breast cancer, colon cancer, pancreatic cancer, prostate cancer, brain cancer and sarcoma, 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 indepedently 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, imi dazolidinyl, 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 cancer is a sarcoma.

3. The method of claim 1 , wherein said cancer is a prostate cancer.

4. The method of claim 1 , wherein said cancer is a breast cancer.

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

6. A method for the treatment of cancer in a mammal, wherein the cancer is selected from the group consisting of uterine cancer, prostate cancer, breast cancer, colon cancer, pancreatic cancer, prostate cancer, brain cancer and sarcoma, 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.

7. The method of claim 6 , wherein said cancer is a sarcoma.

8. The method of claim 6 , wherein said cancer is a prostate cancer.

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

10. The method of claim 6 , wherein said mammal is a human.

11. A method for the treatment of cancer in a mammal, wherein the cancer is selected from the group consisting of uterine cancer, prostate cancer, breast cancer, colon cancer, pancreatic cancer, prostate cancer, brain cancer and sarcoma, 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.

12. The method of claim 11 , wherein said cancer is a sarcoma.

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

14. The method of claim 11 , wherein said cancer is a breast cancer.

15. The method of claim 11 , 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

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D295/26

  Sulfur atoms · CPC title

• A61K31/4453

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

• C07D213/81

  Amides; Imides · CPC title

• C07D213/53

  Nitrogen atoms · CPC title