Use of palovarotene in treatment against HBV virus

Patent metadata

Field	Value
Publication number	US-12569468-B2
Application number	US-202118001167-A
Country	US
Kind code	B2
Filing date	Jun 1, 2021
Priority date	Jun 11, 2020
Publication date	Mar 10, 2026
Grant date	Mar 10, 2026

Abstract

The present application relates to the field of antiviral treatment of hepatitis B, and specifically relates to the use of a compound represented by formula I in treatment against HBV virus.

First claim

What is claimed is:

1 . A method for the treatment of a disease or infection caused by HBV or for anti-HBV treatment, comprising:
administering to a subject in need thereof an effective amount of a compound represented by Formula I, a stereoisomer, a solvate, a pharmaceutically acceptable salt, a hydrate or a solvate of the pharmaceutically acceptable salt, a pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof or a pharmaceutical composition comprising a compound represented by Formula I, a stereoisomer, a solvate, a pharmaceutically acceptable salt, a hydrate or a solvate of the pharmaceutically acceptable salt, a pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof,

wherein R is hydroxyl, amino, C 1-6 alkyl-amino-, di(C 1-6 alkyl)-amino-, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, phenoxy or benzyloxy.

2 . A method for inhibiting the replication or reproduction of HBV in a cell, comprising:
administering to a subject in need thereof an effective amount of a compound represented by Formula I, a stereoisomer, a solvate, a pharmaceutically acceptable salt, a hydrate or a solvate of the pharmaceutically acceptable salt, a pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof or a pharmaceutical composition comprising a compound represented by Formula I, a stereoisomer, a solvate, a pharmaceutically acceptable salt, a hydrate or a solvate of the pharmaceutically acceptable salt, a pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof,

wherein R is hydroxyl, amino, C 1-6 alkyl-amino-, di(C 1-6 alkyl)-amino-, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, phenoxy or benzyloxy.

3 . A method for the clearance of HBV in a cell, comprising:
administering to a subject in need thereof an effective amount of a compound represented by Formula I, a stereoisomer, a solvate, a pharmaceutically acceptable salt, a hydrate or a solvate of the pharmaceutically acceptable salt, a pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof or a pharmaceutical composition comprising a compound represented by Formula I, a stereoisomer, a solvate, a pharmaceutically acceptable salt, a hydrate or a solvate of the pharmaceutically acceptable salt, a pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof,

wherein R is hydroxyl, amino, C 1-6 alkyl-amino-, di(C 1-6 alkyl)-amino-, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkoxy, phenoxy or benzyloxy.

4 . The method according to claim 1 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient, and
the compound, stereoisomer, solvate, pharmaceutically acceptable salt, hydrate or solvate of the pharmaceutically acceptable salt, pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof is present in a therapeutically effective amount.

5 . The method according to claim 1 , wherein the pharmaceutical composition is a solid preparation, an injection, an external preparation, a spray, a liquid preparation, or a compound preparation.

6 . The method according to claim 1 , wherein R is hydroxyl, amino, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, C 5 straight or branched alkyl, C 6 straight or branched alkyl, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy, hexyloxy, methylamino, ethylamino, propylamino, butylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, phenoxy, benzyloxy, chloromethyl, chloroethyl, dichloroethyl, trifluoromethyl, difluoromethyl, monofluoromethyl, chloromethoxy, chloroethoxy, dichloroethoxy, trifluoromethoxy, difluoromethoxy or monofluoromethoxy.

7 . The method according to claim 1 , wherein the disease caused by HBV is viral hepatitis B, or hepatitis B-related cirrhosis or primary liver cancer.

8 . The method according to claim 7 , wherein the viral hepatitis B is chronic viral hepatitis B, acute viral hepatitis B or chronic active hepatitis.

9 . The method according to claim 6 , wherein R is hydroxyl.

10 . The method according to claim 6 , wherein R is amino, methylamino, ethylamino, propylamino, butylamino, dimethylamino, diethylamino, dipropylamino or dibutylamino.

11 . The method according to claim 6 , wherein R is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentyloxy or hexyloxy.

12 . The method according to claim 6 , wherein R is cyclopropoxy, cyclobutoxy, cyclopentyloxy or cyclohexyloxy.

13 . The method according to claim 6 , wherein R is phenoxy or benzyloxy.

14 . The method according to claim 6 , wherein R is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, C 5 straight or branched alkyl, or C 6 straight or branched alkyl.

15 . The method according to claim 6 , wherein R is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

16 . The method according to claim 6 , wherein R is chloromethyl, chloroethyl, dichloroethyl, trifluoromethyl, difluoromethyl or monofluoromethyl.

17 . The method according to claim 6 , wherein R is chloromethoxy, chloroethoxy, dichloroethoxy, trifluoromethoxy, difluoromethoxy or monofluoromethoxy.

18 . The method according to claim 2 , wherein the cell is a cell of mammal.

19 . The method according to claim 2 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient, and the compound, stereoisomer, solvate, pharmaceutically acceptable salt, hydrate or solvate of the pharmaceutically acceptable salt, pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof is present in a therapeutically effective amount.

20 . The method according to claim 3 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient, and the compound, stereoisomer, solvate, pharmaceutically acceptable salt, hydrate or solvate of the pharmaceutically acceptable salt, pharmaceutically acceptable ester, or various pharmaceutically acceptable modifications thereof is present in a therapeutically effective amount.

Assignees

• Yang Sheng Tang Co Ltd
• Univ Xiamen

Inventors

• Zhang Tianying
• Cao Jiali
• Shi Tianshu
• Ma Jian
• Wang Shaojuan
• Yuan Quan
• Zhang Jun
• Xia Ningshao

Classifications

• A61P31/20 Primary

  for DNA viruses · CPC title

• A61K31/415 Primary

  1,2-Diazoles · CPC title