Selective butyrylcholinesterase inhibitor or pharmaceutically acceptable salt thereof, preparation method and use thereof

Patent metadata

Field	Value
Publication number	US-12310944-B2
Application number	US-201916967401-A
Country	US
Kind code	B2
Filing date	Sep 16, 2019
Priority date	Sep 5, 2019
Publication date	May 27, 2025
Grant date	May 27, 2025

Abstract

The present invention discloses a selective butyrylcholinesterase inhibitor having a general formula (I) or a pharmaceutically acceptable salt thereof, a preparation method and use thereof. The treatment efficacy of Alzheimer's disease, especially moderate to severe Alzheimer's disease, is tested through butyrylcholinesterase inhibitory activity, selectivity screening and toxicity to nerve cells as a carrier, and it is found that it has good target activity in vitro, extremely high selectivity and drug safety, can be used as a lead substance for further development of the treatment of Alzheimer's disease by selectively inhibiting butyrylcholinesterase.

First claim

What is claimed is:

1. A selective butyrylcholinesterase inhibitor having a general formula (I) or a pharmaceutically acceptable salt thereof,

wherein n is an integer from 0 to 3;
R 1 represents

furan, pyrrole, pyridine, thiazole, imidazole or cyclohexane;
wherein R 3 represents hydroxyl, C 1 -C 4 carboxyl, C 1 -C 4 aldehyde group, chlorine, bromine, iodine, C 1 -C 4 alkyl, halogen-substituted C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 acyl, cyano, nitro or —NR 5 R 6 , where R 5 and R 6 represent C 1 -C 3 alkyl;
R 2 represents —CH 2 N(CH 3 ) 2 or —CH 2 N(C 3 H 7 ) 2 ;
wherein the selective butyrylcholinesterase inhibitor is selected from the group consisting of:

2. A pharmaceutical composition containing a therapeutically effective amount of one or more selective butyrylcholinesterase inhibitors or a pharmaceutically acceptable salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical composition further contains a pharmaceutically acceptable auxiliary material.

4. The pharmaceutical composition according to claim 2 , wherein the pharmaceutical composition is a tablet, capsule, powder, syrup, liquid, suspension or injection.

5. The selective butyrylcholinesterase inhibitor having a general formula (I) or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the selective butyrylcholinesterase inhibitor is prepared by a preparation method that comprises:
taking 3-aminobenzoic acid as a starting material, forming a corresponding amide intermediate

with an aromatic acid having a different ring system and different substituents, and then reacting with an intermediate

to prepare the selective butyrylcholinesterase inhibitor having general formula (I) or a pharmaceutically acceptable salt thereof;
wherein the reaction scheme is as follows:

6. A method for treating Alzheimer's disease, comprising a step of administering the selective butyrylcholinesterase inhibitor of claim 1 to a subject in need for treating the Alzheimer's disease.

Assignees

• Univ China Pharma

Inventors

• Sun Haopeng
• Yang Hongyu
• Chen Tingkai
• Chen Yao
• Feng Feng
• Du Chenxi

Classifications

• A61K31/4402

  only substituted in position 2, e.g. pheniramine, bisacodyl · CPC title

• A61K31/426

  1,3-Thiazoles · CPC title

• A61K31/4164

  1,3-Diazoles · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K31/341

  not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine · CPC title