# US 10,864,211 B2 · Hydroxy isoxazole compounds useful as GPR120 agonists

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- Number: US 10,864,211 B2
- Document ID: US10864211B2
- Status: Granted
- Kind: B2
- Application number: 16/462,344
- Filed: 2017-12-11
- Published: 2019-09-05
- Granted: 2020-12-15
- Earliest claimed: 2016-12-15
- Assignees: Merck Sharp & Dohme Corp.
- Applicants: Merck Sharp & Dohme Corp.
- Inventors: John S. Debenham; Jason M. Cox; Ping Lan; Zhongxiang Sun; Zhe Feng; Chunrui Sun; W. Michael Seganish; Zhong Lai; Cheng Zhu; Thomas Bara; Murali Rajagopalan; Qun Dang; Hyunjin M. Kim; Bin Hu; Jinglai Hao
- Web page: https://patentgrep.com/patent/US10864211B2

## CPC

- A61K 31/497: containing further heterocyclic rings
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/4858: {Organic compounds}
- A61K 31/42: Oxazoles
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 231/20: One oxygen atom attached in position 3 or 5
- C07D 261/12: Oxygen atoms
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing diabetes, hyperlipidemia, obesity, NASH, inflammation related disorders, and related diseases and conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR120. Pharmaceutical compositions and methods of treatment are also included.

## Claims

### Claim 1

A compound according to the formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is selected from:
(1) aryl and
(2) heteroaryl,
wherein each aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Ra;
B is selected from:
(1) aryl,
(2) —O-aryl,
(3) —(CH2)p—O-aryl,
(4) —O—(CH2)p-aryl,
(5) heteroaryl,
(6) —O-heteroaryl,
(7) —(CH2)p—O-heteroaryl,
(8) —O—(CH2)p-heteroaryl,
(9) —C3-10cycloalkyl,
(10) —(CH2)p—O—C3-10cycloalkyl,
(11) —O—(CH2)p—C3-10cycloalkyl,
(12) —C2-10cycloheteroalkyl,
(13) —(CH2)p—O—C2-10cycloheteroalkyl, and
(14) —O—(CH2)p—C3-10cycloheteroalkyl,
wherein each —CH2, cycloalkyl, cycloheteroalkyl, aryl, and heteroaryl is unsubstituted or substituted with 1, 2 or 3 or 4 substituents selected from Rb;
R1 is selected from:
(1) hydrogen, and
(2) halogen;
R2 is selected from:
(1) halogen,
(2) —C1-6alkyl,
(3) —C2-6alkenyl,
(4) —C2-6alkynyl, and
(5) —CN,
wherein each alkyl, alkenyl and alkynyl is unsubstituted or substituted with 1-3 substituents selected from: halogen, OH, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2 and —OC1-6alkyl;
each Ra is independently selected from:
(1) halogen, and
(2) —C1-6alkyl,
wherein each alkyl is unsubstituted or substituted with 1-3 substituents selected from: —C1-6alkyl and halogen;
each Rb is independently selected from:
(1) halogen,
(2) —CN,
(3) —OH,
(4) —C1-6alkyl,
(5) —C2-6alkenyl,
(6) —C2-6alkynyl,
(7) —O—C1-6alkyl,
(8) —O—C2-6alkenyl,
(9) —O—C2-6alkynyl,
(10) —C3-10 cycloalkyl,
(11) —C3-10cycloalkenyl,
(12) aryl,
(13) heteroaryl,
(14) —OC3-10cycloalkyl,
(15) —OC3-6cycloheteroalkyl,
(16) —O-aryl,
(17) —O-heteroaryl,
(18) —NH2,
(19) —NHC1-6alkyl,
(20) —N(C1-6alkyl)2,
(21) —SC1-6alkyl,
(22) —SOC1-6alkyl, and
(23) —SO2C1-6alkyl,
wherein each alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloheteroalkyl, aryl and heteroaryl is unsubstituted or substituted with 1-3 substituents selected from: —C1-6alkyl, —OC1-6alkyl, —CF3, —OCF3, and halogen;
n is 1 or 2;
m is 0, 1, or 2;
p is 1, 2, or 3; and
q is 0 or 1.

### Claim 2 (depends on 1)

The compound of claim 1 wherein A is aryl, wherein aryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Ra; or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 1)

The compound of claim 1 wherein A is heteroaryl, wherein heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Ra; or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 1)

The compound of claim 1 wherein B is selected from:
(1) aryl,
(2) —O-aryl,
(3) —(CH2)p—O-aryl,
(4) —O—(CH2)p-aryl,
(5) heteroaryl,
(6) —O-heteroaryl,
(7) —O—(CH2)p-heteroaryl,
(8) —C3-10cycloalkyl, and
(9) —O—(CH2)p—C3-10cycloalkyl,
wherein B is unsubstituted or substituted with 1, 2 or 3 or 4 substituents selected from Rb;
or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The compound of claim 1 wherein B is selected from:
(1) aryl,
(2) —O-aryl,
(3) —O—(CH2)p-aryl, and
(4) heteroaryl,
wherein B is unsubstituted or substituted with 1, 2 or 3 substituents selected from Rb; or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 1)

The compound of claim 1 wherein R1 is halogen; or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 1)

The compound of claim 1 wherein R1 is hydrogen; or a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 1)

The compound of claim 1 wherein R2 is selected from:
(1) halogen, and
(2) —C1-6alkyl,
wherein each alkyl is unsubstituted or substituted with 1-3 substituents selected from: halogen, OH, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2 and —OC1-6alkyl; or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The compound of claim 1 wherein R2 is halogen; or a pharmaceutically acceptable salt thereof.

### Claim 10 (depends on 1)

The compound of claim 1 wherein
A is selected from:
(1) aryl, and
(2) heteroaryl,
wherein each aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Ra;
B is selected from:
(1) aryl,
(2) —O-aryl,
(3) —(CH2)p—O-aryl,
(4) —O—(CH2)p-aryl,
(5) heteroaryl,
(6) —O-heteroaryl,
(7) —O—(CH2)p-heteroaryl,
(8) —C3-10cycloalkyl, and
(9) —O—(CH2)p—C3-10cycloalkyl,
wherein B is unsubstituted or substituted with 1, 2 or 3 or 4 substituents selected from Rb;
R1 is selected from:
(1) hydrogen, and
(2) halogen;
R2 is selected from:
(1) halogen, and
(2) —C1-6alkyl,
wherein each alkyl is unsubstituted or substituted with 1-3 substituents selected from:
halogen, OH, —NH2, —NH(C1-6alkyl), —N(C1-6alkyl)2 and —OC1-6alkyl;
n is 1 or 2;
m is 0, 1, or 2;
p is 1, 2, or 3; and
q is 0 or 1;
or a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 1)

The compound of claim 1 wherein
A is selected from:
(1) aryl, and
(2) heteroaryl,
wherein each aryl and heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents selected from Ra;
B is selected from:
(1) aryl,
(2) —O-aryl,
(3) —O—(CH2)p-aryl, and
(4) heteroaryl,
wherein B is unsubstituted or substituted with 1, 2 or 3 substituents selected from Rb;
R1 is hydrogen;
R2 is halogen;
n is 1;
m is 0, or 1;
p is 1, 2, or 3; and
q is 0 or 1;
or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 1)

A compound of claim 1 selected from:
or a pharmaceutically acceptable salt thereof.

### Claim 13 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 in combination with a pharmaceutically acceptable carrier.

### Claim 14 (depends on 1)

A method for the treatment of a condition selected from the group consisting of diabetes, hyperlipidemia, obesity, and inflammation related disorders comprising administering to an individual a pharmaceutical composition comprising the compound of claim 1.