Lappaconitine derivative with analgesic activity, and preparation and application thereof

Patent metadata

Field	Value
Publication number	US-11840517-B2
Application number	US-202217581920-A
Country	US
Kind code	B2
Filing date	Jan 22, 2022
Priority date	Apr 19, 2021
Publication date	Dec 12, 2023
Grant date	Dec 12, 2023

Abstract

Provided herein are a lappaconitine derivative of formula (I), and a preparation and application thereof.

First claim

What is claimed is:

1. A compound of formula (III), or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof

wherein M is O or NH;
R 1 is C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, 5-6 membered aryl or 5-6 membered heteroaryl.

2. A compound of formula (V), or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof

wherein L 1 is absent or C 1-2 alkylene;
n is an integer selected from 0-3;
R 7 is each independently selected from the group consisting of hydrogen, halogenated and unsubstituted C 2-4 alkyl, halogenated and unsubstituted C 1-4 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, NR 3 R 4 , COOR 5 , SO 2 R 6 , halogen, cyano, nitro and phenyl; wherein R 3 , R 4 , R 5 and R 6 are each independently selected from the group consisting of hydrogen and C 1-4 alkyl; and
ring B is 5-6 membered aryl, 5-6 membered heteroaryl, 3-6 membered saturated cycloalkyl, 3-6 membered saturated heterocyclic group, heterofused ring group, bicycloalkyl group or heterobicyclic group.

3. A compound, or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof, the compound being selected from the group consisting of:

4. An analgesic composition, comprising:
the compound of claim 1 , or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.

5. A method for relieving pain in a subject in need thereof, comprising:
administering to the subject a pharmaceutically effective amount of the compound of claim 1 , or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof.

6. The method of claim 5 , wherein a median lethal dose of the compound is higher than a median lethal dose of lappaconitine.

7. An analgesic composition, comprising:
the compound of claim 2 , or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.

8. A method for relieving pain in a subject in need thereof, comprising:
administering to the subject a pharmaceutically effective amount of the compound of claim 2 , or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof.

9. An analgesic composition, comprising:
the compound of claim 3 , or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.

10. A method for relieving pain in a subject in need thereof, comprising:
administering to the subject a pharmaceutically effective amount of the compound of claim 3 , or a stereoisomer, a deuterated compound or a pharmaceutically acceptable salt thereof.

Assignees

• Univ Southwest Jiaotong

Inventors

• Zhou Xianli
• Gao Feng
• Li Xiaohuan
• Li Yuzhu
• Huang Shuai
• Chen Lin
• Zhang Yinyong

Classifications

• C07D223/32 Primary

  containing carbocyclic rings other than six-membered · CPC title

• C07D221/22 Primary

  Bridged ring systems · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title