# US 12,595,261 B2 · P2X3 and/or P2X2/3 receptor antagonist, pharmaceutical composition containing same, and use thereof

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- Number: US 12,595,261 B2
- Document ID: US12595261B2
- Status: Granted
- Kind: B2
- Application number: 17/616,236
- Filed: 2020-06-05
- Published: 2022-10-20
- Granted: 2026-04-07
- Earliest claimed: 2019-06-06
- Assignees: Beijing Tide Pharmaceutical Co., Ltd.
- Applicants: Beijing Tide Pharmaceutical Co., Ltd.
- Inventors: Yanping Zhao; Hongjun Wang; Yeming Wang; Liying Zhou; Yanan Liu
- Web page: https://patentgrep.com/patent/US12595261B2

## CPC

- A61P 11/00: Drugs for disorders of the respiratory system
- C07D 471/04: Ortho-condensed systems
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07D 491/048: the oxygen-containing ring being five-membered
- C07D 495/04: Ortho-condensed systems
- C07D 498/04: Ortho-condensed systems
- C07D 513/04: Ortho-condensed systems
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed are a P2X3 and/or P2X2/3 receptor antagonist of formula (I), a pharmaceutical composition containing same, and the use thereof for preventing or treating a disease regulated by the P2X3 and/or P2X2/3 receptor antagonist.

## Claims

### Claim 1

A compound, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, wherein the compound has the structure of any of the following formulae:
R4 and R5 are each independently selected from the group consisting of H, —C(═O)ORa, —NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —C1-6 alkylene-NRaRb, —C1-6 alkylene-ORa, —C1-6 alkylene-O—C1-6 alkylene-ORa, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, saturated or partially unsaturated C3-10 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl;
the above alkyl, alkylene, alkenyl, alkynyl, cyclic hydrocarbyl, heterocyclyl, aryl, heteroaryl and aralkyl, at each occurrence, are each optionally substituted with one or more substituents independently selected from the group consisting of: halogen, hydroxyl, oxo, amino, cyano, nitro, —Si(R)3, C1-6 alkyl, saturated or partially unsaturated C3-6 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl, C6-12 aralkyl, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORa, —ORa, —SRa, —S(═O)Ra, —S(═O)2Ra, —S(═O)2NRaRb, —NRaRb, —C(═O)NRaRb, —NRa—C(═O)Rb, —NRa—C(═O)ORb, —NRa—S(═O)2—Rb, —NRa—C(═O)—NRaRb, —C1-6 alkylene-NRaRb, —C1-6 alkylene-ORa, —C1-6 alkenylene-ORa and —O—C1-6 alkylene-NRaRb, the alkyl, cyclic hydrocarbyl, heterocyclyl, aryl, heteroaryl and aralkyl are further optionally substituted with one or more substituents independently selected from the group consisting of: halogen, hydroxyl, oxo, amino, cyano, nitro, —NRaRb, C1-6 alkyl, —O—C1-6 alkyl, saturated or partially unsaturated C3-6 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl;
Ra and Rb, at each occurrence, are each independently selected from the group consisting of H, —OH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, saturated or partially unsaturated C3-10 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl; alternatively, Ra and Rb together with the atom to which they are attached form a 3-12-membered heterocycle or heteroaromatic ring, and the above groups are further optionally substituted with one or more substituents independently selected from the group consisting of: halogen, hydroxyl, oxo, amino, cyano, nitro, C1-6 alkyl, —O—C1-6 alkyl, saturated or partially unsaturated C3-6 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl; and
R and R′, at each occurrence, are each independently selected from the group consisting of H, SEM, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, saturated or partially unsaturated C3-10 cyclic hydrocarbyl, saturated or partially unsaturated 3-10-membered heterocyclyl, C6-10 aryl, 5-14-membered heteroaryl and C6-12 aralkyl, and at most 2 ring members in the cyclic hydrocarbyl and heterocyclyl are C(═O).

### Claim 2 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, wherein Ra and Rb, at each occurrence, are each independently selected from the group consisting of H, —OH, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, phenyl, and benzyl, and; alternatively, Ra and Rb together with the atom to which they are attached form a 5-8-membered heterocycle or heteroaromatic ring.

### Claim 3 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, wherein R4 and R5 are each independently selected from the group consisting of H, —C(═O)OC(CH3)3, —NH2, —NHCH3, —NHPh, —NHC(═O)CH3, —NHBoc, methyl, ethyl, —CH2CF3, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl,

### Claim 4 (depends on 1)

The compound according to claim 1, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, wherein the compound has the following structure:

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1, or a pharmaceutically acceptable salt, ester, stereoisomer, polymorph, solvate, N-oxide, or isotopically labeled compound thereof, and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 5)

The pharmaceutical composition according to claim 5, which is in the form of a solid, semi-solid, liquid, or gas preparation.