# US 10,501,489 B2 · C17-alkanediyl and alkenediyl derivatives of oleanolic acid and methods of use thereof

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- Number: US 10,501,489 B2
- Document ID: US10501489B2
- Status: Granted
- Kind: B2
- Application number: 15/433,100
- Filed: 2017-02-15
- Published: 2017-09-14
- Granted: 2019-12-10
- Earliest claimed: 2012-09-10
- Assignees: Reata Pharmaceuticals, Inc.
- Applicants: Reata Pharmaceuticals, Inc.
- Inventors: Christopher F. Bender; Xin Jiang; Eric Anderson; Melean Visnick
- Web page: https://patentgrep.com/patent/US10501489B2

## CPC

- C07J 63/008: {Expansion of ring D by one atom, e.g. D homo steroids}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 39/06: Free radical scavengers or antioxidants
- C07C 255/47: to carbon atoms of rings being part of condensed ring systems
- C07D 207/08: with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D 207/12: Oxygen or sulfur atoms
- C07D 211/46: having a hydrogen atom as the second substituent in position 4
- C07D 213/75: Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- C07D 233/90: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 295/205: Radicals derived from carbonic acid
- C07D 305/08: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms
- C07J: STEROIDS (seco-steroids C07C)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed herein are novel C17-alkanediyl and alkenediyl derivatives of oleanolic acid, including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds. Methods and intermediates useful for making the compounds, and methods of using the compounds, for example, as antioxidant inflammation modulators, and compositions thereof are also provided.

## Claims

### Claim 1

A compound of the formula:
wherein:
n is 1 to 6;
R1 and R2 are each independently —H, —OH, methyl, or as defined below; and
R3 is:
amino or —NHOH; or
N-heteroaryl(C≤8), N-heterocycloalkyl(C≤8), alkylamino(C≤8), dialkylamino(C≤8), alkenylamino(C≤8), alkoxyamino(C≤8), arylamino(C≤8), aralkylamino(C≤8), heteroarylamino(C≤8), heterocycloalkylamino(C≤8), alkylsulfonylamino(C≤8), amido(C≤8), —NH-amido(C≤8), or a substituted version of any of these groups;
R3 and R1, taken together, are —NRa—, wherein Ra is hydrogen or alkyl(C≤4); or
R3 and R2, taken together, are wherein —NRa— is hydrogen or alkyl(C≤4); or
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound of claim 1, further defined as:
wherein:
n is 1 to 6; and
R3 is:
amino or —NHOH; or
N-heteroaryl(C≤8), N-heterocycloalkyl(C≤8), alkylamino(C≤8), dialkylamino(C≤8), alkenylamino(C≤8), alkoxyamino(C≤8), arylamino(C≤8), aralkylamino(C≤8), heteroarylamino(C≤8), heterocycloalkylamino(C≤8), alkyl sulfonylamino(C≤8), amido(C≤8), —NH-amido(C≤8), or a substituted version of any of these groups;
or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound of claim 1, wherein n is 1.

### Claim 4 (depends on 1)

The compound of claim 1, wherein n is 2.

### Claim 5 (depends on 1)

The compound of claim 1, wherein n is 3.

### Claim 6 (depends on 1)

The compound of claim 1, wherein R1 is —H.

### Claim 7 (depends on 1)

The compound of claim 1, wherein R2 is methyl.

### Claim 8 (depends on 1)

The compound of claim 1, wherein R3 is N-heteroaryl(C≤8).

### Claim 9 (depends on 8)

The compound of claim 8, wherein R3 is imidazolyl.

### Claim 10 (depends on 1)

The compound of claim 1, wherein R3 is N-heterocycloalkyl(C≤8).

### Claim 11 (depends on 10)

The compound of claim 10, wherein R3 is morpholinyl or pyrrolidinyl.

### Claim 12 (depends on 1)

The compound of claim 1, wherein R3 is alkylamino(C≤8).

### Claim 13 (depends on 12)

The compound of claim 12, wherein R3 is ethylamino.

### Claim 14 (depends on 1)

The compound of claim 1, further defined as:
or a pharmaceutically acceptable salt thereof.

### Claim 15 (depends on 1)

A pharmaceutical composition comprising:
a) the compound of claim 1; and
b) an excipient.