# US 12,595,249 B2 · Aryl ether-substituted heterocyclic compounds as glpir agonists

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- Number: US 12,595,249 B2
- Document ID: US12595249B2
- Status: Granted
- Kind: B2
- Application number: 19/084,086
- Filed: 2025-03-19
- Published: 2025-10-02
- Granted: 2026-04-07
- Earliest claimed: 2021-08-30
- Assignees: Mindrank Ai Ltd.
- Applicants: Mindrank Ai Ltd
- Inventors: Long Zhang; Zhangming Niu; Bowen Tang
- Web page: https://patentgrep.com/patent/US12595249B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/14: containing three or more hetero rings
- C07D 409/14: containing three or more hetero rings
- C07D 471/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- 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

## Abstract

A novel aryl ether substituted heterocyclic compound has GLP1R agonist activity. Specifically, the compound of formula (I) can be used as a GLP1R agonist. The pharmaceutically acceptable salt, solvate, hydrate, isotope substituent or isomer of the compound are also provided. A method for preventing and/or treating diseases related to the GLP1/GLP1R signaling pathway includes the step of administering to a patient a preventive or therapeutically effective amount the compound, a pharmaceutically acceptable salt, or an enantiomer thereof.

## Claims

### Claim 1

A compound of Formula (IE), pharmaceutically acceptable salts, or enantiomers thereof,
wherein,
=represents a single bond;
X represents —O—;
X′ represents —C(Rd1)(Rd2)—;
L represents —O—;
X1 represents —N—;
X3 represents —N—;
X8 represents —CR5— or —N—;
R is 5- to 8-membered heteroaryl, 3- to 8-membered saturated or partially saturated heterocyclyl, or 3- to 8-membered saturated or partially saturated cycloalkyl, and wherein the heteroaryl, heterocyclyl, and cycloalkyl are optionally substituted with one to multiple substituent groups independently selected from methyl, ethyl, propyl, butyl, 2-methyl-propyl, 1,1-dimethylethyl, pentyl, and hexyl;
each R1 is the same or different and is independently selected from the group consisting of hydrogen, deuterium, halogen, C1-10 alkyl, halogen-substituted C1-10 alkyl, deuterium substituted C1-10 alkyl, and —COOH;
each R4 is the same or different and is independently selected from hydrogen, deuterium, halogen, C1-10 alkyl, and C1-10 alkoxy;
R5 is selected from hydrogen, deuterium, halogen, CN, C1-10 alkyl, C2-10 alkynyl, and C1-10 alkoxy;
each R6 is the same or different and is independently selected from hydrogen, deuterium, halogen, CN, C1-10 alkyl, C2-10 alkynyl, and C1-10 alkoxy;
Rd1 and Rd2 are independently selected from hydrogen, deuterium, halogen, and C1-10 alkyl;
m is an integer selected from 1 and 2;
n is an integer selected from 0, 1 and 2; and
q is an integer selected from 0, 1 and 2.

### Claim 2 (depends on 1)

The compound according to claim 1, pharmaceutically acceptable salts, or enantiomers thereof, wherein R is oxetanyl or imidazolyl, wherein the oxetanyl or imidazolyl is optionally substituted with methyl, ethyl, propyl, butyl, 2-methyl-propyl, 1,1-dimethylethyl, pentyl, or hexyl.

### Claim 3 (depends on 1)

The compound according to claim 1, pharmaceutically acceptable salts, or enantiomers thereof, wherein,
each R1 is the same or different and is independently selected from the group consisting of hydrogen, F and —COOH;
each R4 is the same or different and is independently selected from the group consisting of hydrogen, deuterium, F and methyl;
R5 is selected from the group consisting of hydrogen, deuterium and F;
each R6 is the same or different and is independently selected from the group consisting of hydrogen, deuterium, halogen, ethynyl and CN.

### Claim 4 (depends on 1)

The compound according to claim 1, pharmaceutically acceptable salts, or enantiomers thereof, wherein, m is 1; n is 0; q is 2.

### Claim 5

A compound selected from the following compounds, or
pharmaceutically acceptable salts, or enantiomers thereof:
Number
Structure
Compound 1
Compound 2
Compound 3
Compound 4
Compound 43
Compound 44
Compound 45
Compound 46
Compound C3
Compound C5
Compound C6
Compound C14
Compound C19
Compound C31
Compound C33
Compound C45
Compound C56
Compound C57
Compound C58
Compound C59

### Claim 6 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1.

### Claim 7 (depends on 1)

A method of treating a disease comprising administering to a patient a therapeutically effective amount of a compound of claim 1, wherein the disease is overweight, diabetes, hyperglycemia, insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, adipocyte dysfunction, visceral fat deposition, sleep apnea, obesity, weight gain due to use of other drugs, dyslipidemia, NAFLD, cardiovascular disease, atherosclerosis sclerosis, or peripheral vascular disease.

### Claim 8 (depends on 5)

A method of treating a disease comprising administering to a patient a therapeutically effective amount of a compound of claim 5, or a pharmaceutically acceptable salt or enantiomer thereof, wherein the disease is overweight, diabetes, hyperglycemia, insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, adipocyte dysfunction, visceral fat deposition, sleep apnea, obesity, weight gain due to use of other drugs, dyslipidemia, NAFLD, cardiovascular disease, atherosclerosis sclerosis, or peripheral vascular disease.

### Claim 9 (depends on 5)

A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 5.

### Claim 10 (depends on 7)

The method of claim 7, wherein the disease is overweight or obesity.

### Claim 11 (depends on 7)

The method of claim 7, wherein the disease is diabetes.

### Claim 12 (depends on 8)

The method of claim 8, wherein the disease is overweight or obesity.

### Claim 13 (depends on 8)

The method of claim 8, wherein the disease is diabetes.