Histone deacetylase inhibitors and uses thereof

Patent metadata

Field	Value
Publication number	US-10870618-B2
Application number	US-201716340458-A
Country	US
Kind code	B2
Filing date	Oct 13, 2017
Priority date	Oct 13, 2016
Publication date	Dec 22, 2020
Grant date	Dec 22, 2020

Abstract

Provided herein are compounds of the formula (I) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of cancer.

First claim

What is claimed is:

1. A compound according to formula (I):

wherein:
R 1 is phenyl substituted with —CH 2 NHC(O)-phenyl, or CH 2 NHC(O)C═C-phenyl;
and

R 2 is (i) an alkyl or alkenyl group, optionally substituted with —CF 3 or cycloalkyl, or (ii) halo-lower alkyl,
or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein R 1 is phenyl substituted with —CH 2 NHC(O)-phenyl.

3. The compound according to claim 1 , wherein R 2 is lower alkyl.

4. The compound according to claim 1 , wherein R 2 is halo-lower alkyl.

5. The compound according to claim 1 , wherein R 2 is methyl, ethyl, propyl, butyl, butenyl, isopropyl, propenyl, pentyl, heptyl, octyl, hexyl, decyl, trifluoropropyl, -methylcyclopropyl or -methylcyclobutyl.

6. The compound according to claim 1 , wherein said compound is:
N-(4-(2-butylhydrazine-1-carbonyl)benzyl)benzamide;
(E)-N-(4-(2-(but-2-en-1-yl)hydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-isopropylhydrazine-1-carbonyl)benzyl)benzamide;
(E)-N-(4-(2-propylidenehydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-propylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-pentylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-(3,3,3-trifluoropropyl)hydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-(cyclopropylmethyl)hydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-heptylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-octylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-hexylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-decylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-ethylhydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-(cyclobutylmethyl)hydrazine-1-carbonyl)benzyl)benzamide;
N-(4-(2-ethylhydrazine-1-carbonyl)benzyl)cinnamamide;
N-(4-(2-propylhydrazine-1-carbonyl)benzyl)cinnamamide;
N-(4-(2-butylhydrazine-1-carbonyl)benzyl)cinnamamide;
N-(4-(2-pentylhydrazine-1-carbonyl)benzyl)cinnamamide; or
N-(4-(2-hexylhydrazine-1-carbonyl)benzyl)cinnamamide;
or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. A method for treating cancer, comprising the step of administering a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier to a patient in need thereof, wherein said cancer is acute myeloid leukemia, melanoma or renal.

9. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Musc Found For Res Dev

Inventors

• Chou Chung-Jen James
• Mcclure Jesse
• Zhang Cheng
• Inks Elizabeth

Classifications

• C07D209/14 Primary

  Radicals substituted by nitrogen atoms, not forming part of a nitro radical · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07C243/32

  the carbon skeleton containing rings · CPC title

• C07D213/87

  in position 3 · CPC title

• C07D333/38

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title