# US 10,308,596 B2 · HDAC8 inhibitors for treating cancer

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- Number: US 10,308,596 B2
- Document ID: US10308596B2
- Status: Granted
- Kind: B2
- Application number: 15/042,012
- Filed: 2016-02-11
- Published: 2016-08-18
- Granted: 2019-06-04
- Earliest claimed: 2013-08-20
- Assignees: City of Hope; Taipei Medical University; Academia Sinica
- Applicants: City of Hope; Taipei Medical University; Academia Sinica
- Inventors: Ya-Huei Kuo; Wei-Jan Huang; Chung-I Chang
- Web page: https://patentgrep.com/patent/US10308596B2

## CPC

- C07C 259/06: having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 209/08: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C07D 209/18: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 213/56: Amides
- C07D 213/74: Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C07D 215/14: Radicals substituted by oxygen atoms
- C07D 217/16: substituted by oxygen atoms
- C07D 217/20: with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
- C07D 307/91: Dibenzofurans; Hydrogenated dibenzofurans
- C07D 317/60: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 333/24: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Provided herein, inter alia, are compound and methods of treating cancer by inhibiting HDAC8.

## Claims

### Claim 1

A compound having the formula (I):
wherein:
R1 is substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C3-C7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl; and
R2 is substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C3-C7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein R1 is substituted or unsubstituted C1-C4 alkoxy and R2 is a substituted or unsubstituted C4-C6 aryl.

### Claim 3 (depends on 2)

The compound of claim 2, wherein R1 is unsubstituted C1-C2 alkoxy and R2 is unsubstituted C6 aryl.

### Claim 4 (depends on 1)

The compound of claim 1, wherein the compound has formula (II):

### Claim 5

A compound selected from the group consisting of:

### Claim 6 (depends on 1)

A method of inhibiting HDAC8 mediated deacetylation of p53, the method comprising contacting HDAC8 with the compound of claim 1 in the presence of p53, thereby inhibiting HDAC8 deacetylation of p53.

### Claim 7 (depends on 1)

A method of activating p53 in vivo, the method comprising contacting a cell with the compound of claim 1 in the presence of HDAC8; wherein the cell is an AML cell.

### Claim 8 (depends on 7)

The method of claim 7, wherein the AML cell is an AML stem cell.

### Claim 9 (depends on 1)

The compound of claim 1, wherein:
R1 is substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C6-C7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl; and
R2 is substituted or unsubstituted C1-C20 alkyl, substituted or unsubstituted 2 to 20 membered heteroalkyl, substituted or unsubstituted C3-C7 cycloalkyl, substituted or unsubstituted 3 to 7 membered heterocycloalkyl, substituted or unsubstituted C6-C7 aryl, or substituted or unsubstituted 3 to 7 membered heteroaryl.