# US 12,180,243 B2 · Receptor inhibitor, pharmaceutical composition comprising same, and use thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 12,180,243 B2
- Document ID: US12180243B2
- Status: Granted
- Kind: B2
- Application number: 17/752,960
- Filed: 2022-05-25
- Published: 2023-04-06
- Granted: 2024-12-31
- Earliest claimed: 2018-03-23
- Assignees: Beijing Tide Pharmaceutical Co., Ltd.
- Applicants: Beijing Tide Pharmaceutical Co., Ltd.
- Inventors: Yanping Zhao; Hongjun Wang; Yeming Wang; Xiang Li; Yuanyuan Jiang; Huai Huang; Fajie Li; Liying Zhou; Ning Shao; Fengping Xiao; Zhenguang Zou
- Web page: https://patentgrep.com/patent/US12180243B2

## CPC

- C07F 9/6561: containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 25/00: Drugs for disorders of the nervous system
- C07D 471/08: Bridged systems
- C07D 487/08: Bridged systems
- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention discloses a receptor inhibitor of formula (I), a pharmaceutical composition comprising the same and the use thereof.

## Claims

### Claim 1

A compound or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the compound has a structure of formula (I″):
wherein:
the ring C atom at the position marked with the symbol “*” is connected to the ring C atom at the position marked with the symbol “#” through a U group;
the U group is C1-3 alkylene;
X3 is CR10 or N;
R is
wherein
R1a is selected from the group consisting of C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl, wherein any one of the CH2 moieties in the C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl is optionally replaced with O or S; a saturated or partially unsaturated C3-10 cyclic hydrocarbyl group; a saturated or partially unsaturated 3- to 10-membered heterocyclic group; C6-10 aryl; 5- to 14-membered heteroaryl; —C1-6 alkylene-saturated or partially unsaturated C3-10 cyclic hydrocarbyl group; —C1-6 alkylene-saturated or partially unsaturated 3- to 10-membered heterocyclic group; —C1-6 alkylene-C6-10 aryl; and —C1-6 alkylene-(5- to 14-membered heteroaryl);
R1b is selected from the group consisting of H and R1a;
X1 is CR10 or N;
X4 is selected from the group consisting of C(═O); and —OC(═O)—, —SC(═O)—, and —NR10—C(═O)—, wherein O, S, NR10 are connected to X1;
R′ is
wherein
R2a is selected from the group consisting of C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl, wherein any one of the CH2 moieties in the C1-8 alkyl, C2-8 alkenyl and C2-8 alkynyl is optionally replaced with O or S; a saturated or partially unsaturated C3-10 cyclic hydrocarbyl group; a saturated or partially unsaturated 3- to 10-membered heterocyclic group; C6-10 aryl; 5- to 14-membered heteroaryl; —C1-6 alkylene-saturated or partially unsaturated C3-10 cyclic hydrocarbyl group; —C1-6 alkylene-saturated or partially unsaturated 3- to 10-membered heterocyclic group; —C1-6 alkylene-C6-10 aryl; and —C1-6 alkylene-(5- to 14-membered heteroaryl);
R2b is selected from the group consisting of H and R2a;
X2 is CR10 or N;
X5 is selected from the group consisting of C(═O); and —OC(═O)—, and —SC(═O)—, wherein the O, and S are connected to X2;
provided that one or two of Conditions (i) and (ii) as defined below apply:
(i) R1a and R1b are each independently C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, or 5- to 14-membered heteroaryl, and an available ring atom on R1a is connected to an available ring atom on R1b through Y group, such that R1a and R1b together with X1 to which they are attached form an optionally substituted saturated or partially unsaturated fused ring system containing 3 or more rings; and
(ii) R2a and R2b are each independently C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, or 5- to 14-membered heteroaryl, and an available ring atom on R2a is connected to an available ring atom on R2b through Z group, such that R2a and R2b together with X2 to which they are attached form an optionally substituted saturated or partially unsaturated fused ring system containing 3 or more rings;
wherein
Y is selected from the group consisting of a single bond; NR10; C1-3 alkylene, in which 1 or 2 CH2 moieties are optionally replaced with a group independently selected from the group consisting of O, S, and NR10; and C2-3 alkenylene, in which any one of the CH moieties forming a C═C double bond is optionally replaced with N;
Z is selected from the group consisting of a single bond; NR10; C1-3 alkylene, in which 1 or 2 CH2 moieties are optionally replaced with a group independently selected from the group consisting of O, S, and NR10; and C2-3 alkenylene, in which any one of the CH moieties forming a C═C double bond is optionally replaced with N;
R3 is selected from the group consisting of —C(═O)OH and —C(═O)OC1-6 alkyl;
R4 and R10 are each independently selected from the group consisting of H, halogen, cyano, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —OR11, —SR11, —P(O)(OR11)(OR12), —OC(═O)R11, —C(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)NR11S(═O)yNR11R12, —C(═O)NR11S(═O)yR12, —S(═O)yR11, —S(═O)yOR11, —S(═O)yNR11R12, —S(═O)yNR11S(═O), OR12, —S(═O)yNR11C(═O)R12, —S(═O)yNR11C(═O)OR12, —NR11R12, -NR11-C(═O)R12, —NR11—C(═O)OR12, —NR11—S(═O)y—R12, —NR11—C(═O)—NR11R12, —C1-6 alkylene-R11, —C1-6 alkylene-OR11, —C1-6 alkylene-OC(═O)R11, —C1-6 alkylene-C(═O)OR11, —C1-6 alkylene-S(═O)xR11, —C1-6 alkylene-S(═O)yOR11, —C1-6 alkylene-OC(═O)NR11R12, —C1-6 alkylene-C(═O)NR11R12, —C1-6 alkylene-C(═O)NR11—S(═O)yR12, —C1-6 alkylene-NR11—C(═O)NR11R12, —C1-6 alkylene-OS(═O)yR11, —C1-6 alkylene-OS(═O)yNR11R12, —C1-6 alkylene-S(═O)yNR11R12, —C1-6 alkylene-NR11—S(═O)yNR11R12, —C1-6 alkylene-NR11R12 and —O—C1-6 alkylene-NR11R12;
R11 and R12, at each occurrence, are each independently selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyl-O—, C1-6 alkyl-S—, C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl;
h and k are each independently 1;
the above alkyl, alkylene, alkenyl, alkenylene, alkynyl, cyclic hydrocarbyl group, heterocyclic group, aryl, heteroaryl and aralkyl, at each occurrence, are each optionally substituted by 1, 2, 3 or more R13, wherein the R13, at each occurrence, is independently selected from the group consisting of halogen, cyano, nitro, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl, C6-12 aralkyl, —OR11, —SR11, —P(O)R11R12, —OC(═O)R11, —C(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)NR11S(═O)yNR11R12, —C(═O)NR11S(═O)yR12, —S(═O)yR11, —S(═O)yOR11, —S(═O)yNR11R12, —S(═O)yNR11S(═O)yOR12, —S(═O)yNR11C(═O)R12, S(═O)yNR11C(═O)OR12, —NR11R12, —NR11—C(═O)R12, —NR11—C(═O)OR12, —NR11—S(═O)y—R12, —NR11C(═O)—NR11R12, —C1-6 alkylene-R11, —C1-6 alkylene-OR11, —C1-6 alkylene-OC(═O)R11, —C1-6 alkylene-C(═O)OR11, —C1-6 alkylene-S(═O)xR11, —C1-6 alkylene-S(═O)yOR11, —C1-6 alkylene-OC(═O)NR11R12, —C1-6 alkylene-C(═O)NR11R12, —C1-6 alkylene-C(═O)NR11—S(═O)yR12, —C1-6 alkylene-NR11C(═O)NR11R12, —C1-6 alkylene-OS(═O)yR11, —C1-6 alkylene-OS(═O)yNR11R12, —C1-6 alkylene-S(═O)yNR11R12, —C1-6 alkylene-NR11—S(═O)yNR11R12, —C1-6 alkylene-NR11R12, and —O—C1-6 alkylene-NR11R12, and wherein the alkyl, alkylene, cyclic hydrocarbyl group, heterocyclic group, aryl, heteroaryl and aralkyl recited for the substituent R13 are optionally further substituted by 1, 2, 3 or more substituents independently selected from the group consisting of halogen, OH, oxo, amino, cyano, nitro, C1-6 alkyl, halogenated C1-6 alkyl, hydroxy C1-6 alkyl, C3-6 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, 5- to 14-membered heteroaryl and C6-12 aralkyl; and wherein the heterocyclic group, aryl or heteroaryl when being a substituent is connected to the rest of the molecule through a ring C atom, or where possible, through a ring N atom;
x, at each occurrence, is independently 0, 1 or 2; and
y and z, at each occurrence, are each independently 1 or 2.

### Claim 2 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X5 is C(═O), or —O—C(═O)— wherein the O is connected to X2.

### Claim 3 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X5 is C(═O).

### Claim 4 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the compound has a structure of formula (IV):

### Claim 5 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the U group is methylene or ethylene.

### Claim 6 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R3 is COOH, COOCH3 or COOCH2CH3.

### Claim 7 (depends on 6)

The compound according to claim 6, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R3 is COOH.

### Claim 8 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R4 and R10, at each occurrence, are each independently H, F, Cl, Br, I, amino, cyano, nitro, C1-4 alkyl, C5-7 cyclic hydrocarbyl group, 5- to 7-membered monocyclic heterocyclic group, phenyl, 5- to 6-membered heteroaryl, —OR11, —SR11, —OC(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)NR11S(═O)yNR11R12, —C(═O)NR11S(═O)yR12, —S(═O)yOR11, —S(═O)yNR11R12, —S(═O)yNR11C(═O)R12, —S(═O)yNR11C(═O)OR12, —C1-4 alkylene-OR11, —C1-4 alkylene-OC(═O)R11, —C1-4 alkylene-C(═O)OR11, —C1-4 alkylene-S(═O)yOR11, —C1-4 alkylene-OC(═O)NR11R12, —C1-4 alkylene-C(═O)NR11R12, —C1-4 alkylene-OS(═O)yR11 or —C1-4 alkylene-S(═O)yNR11R12.

### Claim 9 (depends on 8)

The compound according to claim 8, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R4 and R10, at each occurrence, are each independently H, F, Cl, Br, I, OH, amino, cyano, nitro or C1-4 alkyl.

### Claim 10 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R11 and R12 at each occurrence are each independently selected from the group consisting of H, C1-4 alkyl, C5-7 cyclic hydrocarbyl group, 5- to 7-membered monocyclic heterocyclic group, phenyl, 5- to 6-membered heteroaryl, wherein the C1-4 alkyl, cyclic hydrocarbyl group, heterocyclic group, phenyl and heteroaryl are each optionally substituted by 1, 2, 3 or more R13.

### Claim 11 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein
R13, at each occurrence, is independently selected from the group consisting of F, Cl, Br, I, amino, cyano, nitro, C1-4 alkyl, C5-7 cyclic hydrocarbyl group, 5- to 7-membered monocyclic heterocyclic group, phenyl, 5- to 6-membered heteroaryl, C6-12 aralkyl, —OR11, —SR11, —OC(═O)R11, —C(═O)OR11, —C(═O)NR11R12, —C(═O)NR11S(═O)yNR11R12, —C(═O)NR11S(═O)yR12, —S(═O)yOR11, —S(═O)yNR11R12, —S(═O)yNR11C(═O)R12, —S(═O)yNR11C(═O)OR12, —C1-4 alkylene-R11, —C1-4 alkylene-OR11, —C1-4 alkylene-OC(═O)R11, —C1-4 alkylene-C(═O)OR11, —C1-4 alkylene-S(═O)yOR11, —C1-4 alkylene-OC(═O)NR11R12, —C1-4 alkylene-C(═O)NR11R12, —C1-4 alkylene-OS(═O)yR11 or —C1-4 alkylene-S(═O)yNR11R12; and
wherein the alkyl, alkylene, cyclic hydrocarbyl group, heterocyclic group, phenyl and heteroaryl are optionally further substituted by 1, 2, 3 or more substitutes independently selected from the group consisting of F, Cl, Br, I, OH, oxo, amino, cyano, nitro, C1-4 alkyl, halogenated C1-4 alkyl, C5-6 cyclic hydrocarbyl group, 5- to 7-membered monocyclic heterocyclic group, phenyl, 5- to 6-membered heteroaryl.

### Claim 12 (depends on 11)

The compound according to claim 11, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the alkyl, alkylene, cyclic hydrocarbyl group, heterocyclic group, phenyl and heteroaryl are optionally further substituted by 1, 2, 3 or more substitutes independently selected from the group consisting of F, Cl, OH, amino, cyano, nitro, C1-4 alkyl and halogenated C1-4 alkyl.

### Claim 13 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13, at each occurrence, is independently selected from the group consisting of
—P(O)R11R12, wherein R11 and R12, at each occurrence, are optionally each independently a C1-6 alkyl optionally substituted by 1, 2, 3 or more halogens; and
C3-10 cyclic hydrocarbyl group or 3- to 10-membered heterocyclic group, which is substituted by C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted by 1, 2, 3 or more OH or halogens.

### Claim 14 (depends on 13)

The compound according to claim 13, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13, at each occurrence, is independently C3-7 cyclic hydrocarbyl group or 4- to 7-membered heterocyclic group, which is substituted by C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted by 1, 2, 3 or more OH or halogens.

### Claim 15 (depends on 13)

The compound according to claim 13, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the halogens are selected from F and Cl.

### Claim 16 (depends on 14)

The compound according to claim 14, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the halogens are selected from F and Cl.

### Claim 17 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein
R1a is an optionally substituted group selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cyclic hydrocarbyl group, 4- to 7-membered monocyclic heterocyclic group, 8- to 10-membered benzo-fused heterocyclic group, phenyl, 5- to 10-membered heteroaryl, —C1-3 alkylene-C3-7 cyclic hydrocarbyl group, —C1-3 alkylene-(5- to 7-membered monocyclic heterocyclic group), —C1-3 alkylene-(8- to 10-membered benzo-fused heterocyclic group), —C1-3 alkylenephenyl and —C1-3 alkylene-(5- to 10-membered heteroaryl); and
wherein said “optionally substituted” means optionally substituted by 1, 2, 3 or more R13.

### Claim 18 (depends on 17)

The compound according to claim 17, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein
R1a is an optionally substituted group selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C5-7 cyclic hydrocarbyl group, 4- to 7-membered monocyclic heterocyclic group (including 5-, 6- or 7-membered monocyclic heterocyclic group), 8- to 10-membered benzo-fused heterocyclic group, phenyl, 5- to 10-membered heteroaryl (including 5- to 6-membered heteroaryl), —C1-3 alkylene-C3-7 cyclic hydrocarbyl group, —C1-3 alkylene-(5- to 7-membered monocyclic heterocyclic group), —C1-3 alkylenephenyl and —C1-3 alkylene-(5- to 6-membered heteroaryl), and wherein said “optionally substituted” means optionally substituted by 1, 2, 3 or more R13 moieties.

### Claim 19 (depends on 17)

The compound according to claim 17, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of C1-4 alkyl-O—; halogen (including F, Cl, Br and I); and C1-4 alkyl or phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected from halogen.

### Claim 20 (depends on 18)

The compound according to claim 18, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of C1-4 alkyl-O—; halogen (including F, Cl, Br and I); and C1-4 alkyl or phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected from halogen.

### Claim 21 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X4 is C(═O); or —OC(═O)—, or —NR10—C(═O)—, wherein the O and NR10 are connected to X1.

### Claim 22 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X4 is C(═O); or —O—C(═O)—, wherein the O is connected to X1.

### Claim 23 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X1 is CH.

### Claim 24 (depends on 22)

The compound according to claim 22, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
R1a is a group selected from the group consisting of an optionally substituted C3-7 cyclic hydrocarbyl group, an optionally substituted 4- to 7-membered monocyclic heterocyclic group, an optionally substituted 8- to 10-membered benzo-fused heterocyclic group, an optionally substituted phenyl, an optionally substituted 5- to 10-membered heteroaryl, -optionally substituted C1-3 alkylene-(optionally substituted C3-7 cyclic hydrocarbyl group), -optionally substituted C1-3 alkylene-(optionally substituted 5- to 7-membered monocyclic heterocyclic group), -optionally substituted C1-3 alkylene-(optionally substituted 8- to 10-membered benzo-fused heterocyclic group), -optionally substituted C1-3 alkylene-optionally substituted phenyl, and -optionally substituted C1-3 alkylene-(optionally substituted 5- to 10-membered heteroaryl);
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 25 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1a is a group selected from the group consisting of an optionally substituted C3-7 cyclic hydrocarbyl group, an optionally substituted 4- to 7-membered monocyclic heterocyclic group, an optionally substituted 8- to 10-membered benzo-fused heterocyclic group, an optionally substituted phenyl, an optionally substituted 5- to 10-membered heteroaryl, —C1-3 alkylene-(optionally substituted C3-7 cyclic hydrocarbyl group), —C1-3 alkylene-(optionally substituted 5- to 7-membered monocyclic heterocyclic group), —C1-3 alkylene-(optionally substituted 8- to 10-membered benzo-fused heterocyclic group), —C1-3 alkylene-optionally substituted phenyl, and —C1-3 alkylene-(optionally substituted 5- to 10-membered heteroaryl);
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 26 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1a is a group selected from the group consisting of
an optionally substituted phenyl;
—C1-3 alkylene-(optionally substituted C3-7 cyclic hydrocarbyl group), wherein the cyclic hydrocarbyl group is optionally selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl;
—C1-3 alkylene-(optionally substituted 8- to 10-membered benzo-fused heterocyclic group), wherein the heterocyclic group is optionally selected from
—C1-3 alkylene-optionally substituted phenyl;
an optionally substituted 5- to 10-membered heteroaryl and —C1-3 alkylene-(optionally substituted 5- to 10-membered heteroaryl), wherein the heteroaryl is optionally selected from
and
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 27 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of:
halogen, —OR11 wherein R11 herein is optionally a C1-6 alkyl optionally substituted by 1, 2, 3 or more halogens, cyano and C3-7 cyclic hydrocarbyl group; and C1-4 alkyl, C2-4 alkenyl and C2-4 alkynyl which are optionally substituted by 1, 2, 3 or more halogens, and —NR11R12 wherein R11 and R12 here are each independently selected from the group consisting of H and C1-4 alkyl;
—P(O)R11R12 wherein here R11 and R12, at each occurrence, are each independently a C1-6 alkyl optionally substituted by 1, 2, 3 or more halogens; and
C3-10 cyclic hydrocarbyl group or 3- to 10-membered heterocyclic group, which is substituted by C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted by 1, 2, 3 or more OH or halogens and wherein the halogens here are optionally selected from F and Cl.

### Claim 28 (depends on 27)

The compound according to claim 27, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R11 in said —OR11 is C1-3 alkyl optionally substituted by 1, 2 or 3 F or Cl.

### Claim 29 (depends on 27)

The compound according to claim 27, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of:
F, Cl, Br, OH, —OC1-4 alkyl, —N(C1-4 alkyl)2, cyano, C3-7 cyclic hydrocarbyl group, C2-4 alkenyl and C2-4 alkynyl; and C1-4alkyl optionally substituted by 1, 2, 3 or more F, Cl or Br;
—P(O)R11R12 wherein R11 and R12, at each occurrence, are each independently a C1-3 alkyl optionally substituted by 1, 2 or 3 F or Cl; and
C3-7 cyclic hydrocarbyl group or 4- to 7-membered heterocyclic group, which is substituted by C1-6 alkyl, wherein the C1-6 alkyl is optionally substituted by 1, 2, 3 or more OH or halogens and wherein the halogens here are optionally selected from F and Cl.

### Claim 30 (depends on 27)

The compound according to claim 27, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of:
F, Cl, Br, —OCH3, —N(CH3)2, cyano, cyclopropyl, vinyl, 1-propenyl, 2-propenyl, ethynyl, 1-propenyl, 2-propynyl, methyl, ethyl, n-propyl, isopropyl, tert-butyl and CF3;
—P(O)R11R12 wherein R11 and R12, at each occurrence, are each independently a C1-3 alkyl optionally substituted by 1, 2 or 3 F or Cl; and
C5-7 cyclic hydrocarbyl group or 5- to 7-membered monocyclic heterocyclic group, which is substituted by C1-3 alkyl, wherein the C1-3 alkyl is optionally substituted by 1, 2, 3 or more OH or halogens and wherein the halogens here are optionally selected from F and Cl.

### Claim 31 (depends on 27)

The compound according to claim 27, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of:
—P(O)R11R12 wherein R11 and R12, at each occurrence, are each independently methyl, ethyl, propyl or isopropyl; and
C5-7 cyclic hydrocarbyl group or 5- to 7-membered monocyclic heterocyclic group, which is substituted by C1-3 alkyl, wherein the C1-3 alkyl is optionally substituted by 1, 2 or 3 OH, F or Cl.

### Claim 32 (depends on 27)

The compound according to claim 27, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is —P(O)R11R12 wherein R11 and R12, at each occurrence, are each independently methyl.

### Claim 33 (depends on 27)

The compound according to claim 27, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1a is selected from the group consisting of

### Claim 34 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1b is a group selected from the group consisting of H, an optionally substituted C1-4 alkyl, an optionally substituted C3-7 cyclic hydrocarbyl group, an optionally substituted phenyl, -optionally substituted C1-3 alkylene-(optionally substituted C3-7 cyclic hydrocarbyl group), and -optionally substituted C1-3 alkylene-optionally substituted phenyl;
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 35 (depends on 34)

The compound according to claim 34, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1b is a group selected from the group consisting of H, an optionally substituted C1-4 alkyl, an optionally substituted C3-7 cyclic hydrocarbyl group, an optionally substituted phenyl, —C1-3 alkylene-(optionally substituted C3-7 cyclic hydrocarbyl group), and —C1-3 alkylene-optionally substituted phenyl;
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 36 (depends on 34)

The compound according to claim 34, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1b is a group selected from the group consisting of
H, phenyl;
an optionally substituted C1-4 alkyl, the alkyl being optionally selected from methyl, ethyl and isopropyl;
an optionally substituted C3-7 cyclic hydrocarbyl group and —C1-3 alkylene-(C3-7 cyclic hydrocarbyl group), the cyclic hydrocarbyl group being optionally selected from cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; and
—C1-3 alkylene-phenyl; and
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 37 (depends on 34)

The compound according to claim 34, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of halogen and C1-4 alkyl.

### Claim 38 (depends on 37)

The compound according to claim 37, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is elected from the group consisting of F, Cl, Br and methyl.

### Claim 39 (depends on 34)

The compound according to claim 34, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R1b is selected from the group consisting of H, methyl, ethyl, isopropyl, CF3CH2, cyclopropyl,
phenyl,

### Claim 40 (depends on 34)

The compound according to claim 34, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X1 is CH or N.

### Claim 41 (depends on 40)

The compound according to claim 40, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X1 is N.

### Claim 42 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X4 is C(═O).

### Claim 43 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R3 is COOH; and R4 is H.

### Claim 44 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
R2a is selected from the group consisting of an optionally substituted phenyl, and -optionally substituted C1-3 alkylene-optionally substituted phenyl; and/or
R2b is selected from the group consisting of an optionally substituted C1-4 alkyl, an optionally substituted phenyl, and -optionally substituted C1-3 alkylene-optionally substituted phenyl;
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 45 (depends on 44)

The compound according to claim 44, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
R2a is selected from the group consisting of an optionally substituted phenyl, and —C1-3 alkylene-optionally substituted phenyl; and/or
R2b is selected from the group consisting of C1-4 alkyl, an optionally substituted phenyl, and —C1-3 alkylene-optionally substituted phenyl;
wherein the term “optionally substituted” means being substituted by 1, 2, 3 or more R13.

### Claim 46 (depends on 44)

The compound according to claim 44, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of halogen and —OR11, and wherein R11 is selected from C1-4 alkyl.

### Claim 47 (depends on 44)

The compound according to claim 44, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R13 is selected from the group consisting of F, Cl, Br and —OCH3.

### Claim 48 (depends on 44)

The compound according to claim 44, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
R2a is selected from the group consisting of phenyl,
and/or
R2b is selected from the group consisting of methyl, phenyl,

### Claim 49 (depends on 24)

The compound according to claim 24, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the compound has a structure of formula (II):

### Claim 50 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R is:

### Claim 51 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein Y is a single bond, NR10, O, S, methylene, ethylene, —CH2—O—, —O—CH2—, —CH2—S—, —S—CH2—, —CH2—NR10—, —NR10—CH2—, —CH═CH—, —CH═N— or —N═CH—.

### Claim 52 (depends on 51)

The compound according to claim 51, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein
the optionally substituted saturated or partially unsaturated fused ring system comprising 3 or more rings which is formed by R1a and R1b together with X1 to which they are attached has a structure of formula (a):
wherein:
ring A and ring B are each independently C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl, or 5- to 14-membered heteroaryl;
“” represents a single bond or a double bond;
R5a and R5b, at each occurrence, are each independently R10;
R7 does not exist or is R10; and
m and n, at each occurrence, are each independently 0, 1, 2 or 3.

### Claim 53 (depends on 52)

The compound according to claim 52, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the ring A and the ring B are each independently C5-7 cyclic hydrocarbyl group, 5- to 7-membered monocyclic heterocyclic group, phenyl, or 5- to 6-membered heteroaryl.

### Claim 54 (depends on 53)

The compound according to claim 53, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the C5-7 cyclic hydrocarbyl group is cyclopentyl or cyclohexyl.

### Claim 55 (depends on 52)

The compound according to claim 52, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the fused ring system has a structure of formula (1) or formula (2):

### Claim 56 (depends on 52)

The compound according to claim 52, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X1 is CH or N.

### Claim 57 (depends on 55)

The compound according to claim 55, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
the group of formula (1) has a structure selected from the group consisting of
the group of formula (2) has a structure selected from the group consisting of

### Claim 58 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein
R2a is an optionally substituted group selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C5-7 cyclic hydrocarbyl group, 5-, 6- or 7-membered monocyclic heterocyclic group, 8- to 10-membered benzo-fused heterocyclic group, phenyl, 5- to 6-membered heteroaryl, —C1-3 alkylene-C3-7 cyclic hydrocarbyl group, —C1-3 alkylene-(5- to 7-membered monocyclic heterocyclic group), —C1-3 alkylenephenyl and —C1-3 alkylene-(5- to 6-membered heteroaryl), and wherein said “optionally substituted” means optionally substituted by 1, 2, 3 or more R13;
wherein R13 is optionally selected from the group consisting of C1-4 alkyl-O—; halogen (including F, Cl, Br, and I); and C1-4 alkyl or phenyl, which is optionally substituted by 1, 2 or 3 substituents independently selected from halogen.

### Claim 59 (depends on 58)

The compound according to claim 58, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X2 is CR10 or N, and wherein R10 is optionally H, OH or C1-4 alkyl.

### Claim 60 (depends on 59)

The compound according to claim 59, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X2 is CH.

### Claim 61 (depends on 1)

The compound according to claim 1, or the pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein R′ is:

### Claim 62 (depends on 1)

The compound according to claim 1, or the pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein Z is a single bond, NR10, O, S, methylene, ethylene, —CH2—O—, —O—CH2—, —CH2—S—, —S—CH2—, —CH2—NR10—, —NR10—CH2—, —CH═CH—, —CH═N— or —N═CH—.

### Claim 63 (depends on 62)

The compound according to claim 62, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein
the optionally substituted saturated or partially unsaturated fused ring system comprising 3 or more rings which is formed by R2a and R2b together with X2 to which they are attached has a structure of formula (b):
wherein:
ring C and ring D are each independently C3-10 cyclic hydrocarbyl group, 3- to 10-membered heterocyclic group, C6-10 aryl or 5- to 14-membered heteroaryl;
“” represents a single bond or a double bond;
R6a and R6b, at each occurrence, are each independently R10;
R8 does not exist or is R10; and
p and q, at each occurrence, are each independently 0, 1, 2 or 3.

### Claim 64 (depends on 63)

The compound according to claim 63, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the ring C and the ring D are each independently C5-7 cyclic hydrocarbyl group, 5- to 7-membered monocyclic heterocyclic group, phenyl or 5- to 6-membered heteroaryl.

### Claim 65 (depends on 63)

The compound according to claim 63, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the fused ring system has a structure of formula (3) or formula (4):

### Claim 66 (depends on 63)

The compound according to claim 63, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein X2, at each occurrence, is independently CR10 or N, and wherein R10 is H, OH, amino or C1-4 alkyl.

### Claim 67 (depends on 65)

The compound according to claim 65, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
the group of formula (3) has a structure selected from the group consisting of
or
the group of formula (4) has a structure selected from the group consisting of

### Claim 68 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein:
the compound has the structure of formula (a-1), (a-3), (a-5), or (a-7):
wherein:
R5a and R5b, at each occurrence, are each independently R10;
R7 does not exist or is R10;
m and n, at each occurrence, are each independently 0, 1, 2 or 3;
R6a and R6b, at each occurrence, are each independently R10;
R8 does not exist or is R10; and
p and q, at each occurrence, are each independently 0, 1, 2 or 3.

### Claim 69 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, wherein the compound has a structure of
No.
Structure
C6
C7
C8
C9
C10
C20
C21
C22
C23
C24
C25
C26
C27
C38
C39
C40
C42
C43
C44
C45
C46
C47
C48
C49
C50
C51
C52
C53
C54
C55
C56
C57
C58
C59
C60
C71
C72
C73
C74
C77
C80
C81

### Claim 70 (depends on 1)

A pharmaceutical composition comprising a prophylactically or therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, and a pharmaceutically acceptable carrier.

### Claim 71 (depends on 1)

A method for the prophylaxis or the treatment of an AT2 receptor-mediated disorder or a symptom associated therewith, comprising administering to a subject in need thereof an effective amount of the compound of claim 1 or a pharmaceutically acceptable salt, stereoisomer, or N-oxide thereof, or a pharmaceutical composition containing the compound of claim 1, wherein the AT2 receptor-mediated disorder is peripheral neuropathy, neuralgia, or neuropathic pain.

### Claim 72 (depends on 71)

The method of claim 71,
wherein the AT2 receptor-mediated disorder is peripheral neuropathy.

### Claim 73 (depends on 72)

The method of claim 72, wherein the AT2 receptor -mediated disorder is neuralgia.

### Claim 74 (depends on 73)

The method of claim 73, wherein the AT2 receptor -mediated disorder is neuropathic pain.