# US 12,600,729 B2 · New-type benzazepine fused ring derivative

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- Number: US 12,600,729 B2
- Document ID: US12600729B2
- Status: Granted
- Kind: B2
- Application number: 18/547,513
- Filed: 2022-03-04
- Published: 2024-06-13
- Granted: 2026-04-14
- Earliest claimed: 2021-03-05
- Assignees: Shanghai Jeyou Pharmaceutical Co., Ltd.
- Applicants: Shanghai Jeyou Pharmaceutical Co., Ltd.
- Inventors: Hongfu Lu; Dezhi Qiu; Jianbiao Peng
- Web page: https://patentgrep.com/patent/US12600729B2

## CPC

- C07D 487/04: Ortho-condensed systems
- C07D 491/044: with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/12: of the kidneys
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 25/00: Drugs for disorders of the nervous system
- C07D 491/048: the oxygen-containing ring being five-membered
- 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 benzazepine fused ring derivative as represented by formula (I) or a pharmaceutically acceptable salt thereof, and the use of a compound in the diagnosis, prevention and/or treatment of diseases related to vasopressin receptors.

## Claims

### Claim 1

A compound of formula (I), an optical isomer thereof, or a pharmaceutically acceptable salt thereof,
wherein
ring A is selected from 4- to 6-membered heterocyclyl and C3-6 cycloalkyl, and the 4- to 6-membered heterocyclyl or C3-6 cycloalkyl is optionally substituted by 1, 2, or 3 RA;
ring B is selected from phenyl and 5- to 6-membered heteroaryl, and the phenyl or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R3;
ring C is selected from phenyl and 5- to 6-membered heteroaryl, and the phenyl or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R4;
T1, T2 are each independently selected from N and C(RT);
R1, R2, R3, RA, RT are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, and C1-6 heteroalkyl, and the C1-6 alkyl or C1-6 heteroalkyl is optionally substituted by 1, 2, or 3 R;
each R4 is independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, and 5- to 6-membered heteroaryl, and the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R4a;
R, R4a are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino, and the C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino are optionally substituted by 1, 2, or 3 R′;
R′ is selected from H, F, Cl, Br, I, CN, OH, NH2, and C1-6 alkyl;
m1, m2 are each independently selected from 0, 1, or 2;
and when ring A is selected from 4- to 6-membered heterocyclyl, the compound of formula (I) is not selected from
the 4- to 6-membered heterocyclyl, C1-6 heteroalkyl, or 5- to 6-membered heteroaryl comprises 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from —O—, —NH—, —S—, —C(═O)—, —C(═O)O—, —S(═O)—, —S(═O)2—, and N.

### Claim 2 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein the compound has a structure of formula (II),
wherein X1, X2, X3 are each independently selected from O, C(RA)2, and NRA;
ring B is selected from phenyl and 5- to 6-membered heteroaryl, and the phenyl or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R3;
ring C is selected from phenyl and 5- to 6-membered heteroaryl, and the phenyl or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R4;
T1, T2 are each independently selected from N and C(RT);
R1, R2, R3, RA, RT are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, and C1-6 heteroalkyl, and the C1-6 alkyl or C1-6 heteroalkyl is optionally substituted by 1, 2, or 3 R;
each R4 is independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, and 5- to 6-membered heteroaryl, and the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R4a;
R, R4a are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino, and the C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino are optionally substituted by 1, 2, or 3 R′;
R′ is selected from H, F, Cl, Br, I, CN, OH, NH2, and C1-6 alkyl;
m1, m2, n are each independently selected from 0, 1, or 2;
and when X1, X3 are selected from O at the same time, the compound of formula (II) is not selected from
the C1-6 heteroalkyl or 5- to 6-membered heteroaryl comprises 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from —O—, —NH—, —S—, —C(═O)—, —C(═O)O—, —S(═O)—, —S(═O)2—, and N.

### Claim 3 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein the compound has a structure of formula (III),
wherein X1, X2, X3 are each independently selected from O, C(RA)2, and NRA;
T1, T2 are each independently selected from N and C(RT);
Y1, Y2 are each independently selected from N and C(RY);
R1, R2, R3, RA, RT, RY are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, and C1-6 heteroalkyl, and the C1-6 alkyl or C1-6 heteroalkyl is optionally substituted by 1, 2, or 3 R;
each R4 is independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, and 5- to 6-membered heteroaryl, and the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R4a;
R, R4a are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino, and the C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino are optionally substituted by 1, 2, or 3 R′;
R′ is selected from H, F, Cl, Br, I, CN, OH, NH2, and C1-6 alkyl;
m1, m2, m3, m4, n are each independently selected from 0, 1, or 2;
and when X1, X3 are selected from O at the same time, the compound of formula (III) is not selected from
the C1-6 heteroalkyl or 5- to 6-membered heteroaryl comprises 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from —O—, —NH—, —S—, —C(═O)—, —C(═O)O—, —S(═O)—, —S(═O)2—, and N.

### Claim 4 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein the compound has a structure of formula (IV),
wherein T1, T2 are each independently selected from O, N, and C(RT);
Y1, Y2 are each independently selected from N and C(RY);
R1, R2, R3, RA, RT, RY are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, and C1-6 heteroalkyl, and the C1-6 alkyl or C1-6 heteroalkyl is optionally substituted by 1, 2, or 3 R;
each R4 is independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, and 5- to 6-membered heteroaryl, and the C1-6 alkyl, C1-6 alkoxy, C1-6 alkylamino, C3-6 cycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted by 1, 2, or 3 R4a;
R, R4a are each independently selected from H, F, Cl, Br, I, CN, OH, NH2, C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino, and the C1-6 alkyl, C1-6 alkoxy, and C1-6 alkylamino are optionally substituted by 1, 2, or 3 R′;
R′ is selected from H, F, Cl, Br, I, CN, OH, NH2, and C1-6 alkyl;
m2, m3, n are each independently selected from 0, 1, or 2;
the C1-6 heteroalkyl or 5- to 6-membered heteroaryl comprises 1, 2, 3, or 4 heteroatoms or heteroatom groups independently selected from —O—, —NH—, —S—, —C(═O)—, —C(═O)O—, —S(═O)—, —S(═O)2—, and N.

### Claim 5 (depends on 4)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 4, wherein the compound has a structure of formula (V-1), (V-2), (V-3), or (V-4),

### Claim 6 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein R4 is selected from H, F, Cl, Br, I, CN, OH, NH2, CH3, CF3,
cyclopropyl, cyclobutyl, cyclopentyl, phenyl, pyridyl, pyrimidinyl, thienyl, and thiazolyl.

### Claim 7 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein ring A is selected from azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, cyclobutyl, cyclopentyl, and cyclohexyl, and the azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, cyclobutyl, cyclopentyl, or cyclohexyl is optionally substituted by 1 or 2 RA.

### Claim 8 (depends on 7)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 7, wherein ring A is selected from

### Claim 9 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein ring B is selected from phenyl and pyridyl, and the phenyl or pyridyl is optionally substituted by 1, 2, or 3 R3.

### Claim 10 (depends on 9)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 9, wherein ring B is selected from

### Claim 11 (depends on 1)

The compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1, wherein ring C is selected from

### Claim 12

A compound of the following formula, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, selected from:

### Claim 13 (depends on 1)

A method for preventing or treating diseases related to arginine vasopressin V1a receptor, arginine vasopressin V1b receptor, arginine vasopressin V2 receptor, sympathetic nervous system, or renin-angiotensin-aldosterone system in a subject in need thereof, comprising administering the compound, the optical isomer thereof, or the pharmaceutically acceptable salt thereof according to claim 1 to the subject.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the diseases related to arginine vasopressin V1a receptor, arginine vasopressin V1b receptor, arginine vasopressin V2 receptor, sympathetic nervous system, or renin-angiotensin-aldosterone system comprise: hypertension, Reye's syndrome, dysmenorrhea, premature delivery, corticotropin-releasing hormone secretion disorder, adrenal hyperplasia, depression, chronic congestive heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone secretion, hyponatremia caused by chronic heart failure/liver cirrhosis/inappropriate antidiuretic hormone secretion, or polycystic kidney disease.

### Claim 15

A compound of the following formula, an optical isomer thereof, or a pharmaceutically acceptable salt thereof, selected from: