185104-11-4

Basic information

• Product Name: N-[2-[Bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-4-thiazolecarboxamide hydrochloride
• Synonyms: Acotiamide hydrochloride;N-[2-[Bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-4-thiazolecarboxamide hydrochloride;N-[2-[Bisisopropylamino]-ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-4-thiazolecarboxamide HCl
• CAS NO: 185104-11-4
• Molecular Formula: C21H30N4O5S.HCl
• Molecular Weight: 487.01264
• EINECS: 203-105-6
• Mol File: 185104-11-4.mol
• Article Data: 11

Chemical Properties

• Appearance: /
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• CAS DataBase Reference: N-[2-[Bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-4-thiazolecarboxamide hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: N-[2-[Bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-4-thiazolecarboxamide hydrochloride(185104-11-4)
• EPA Substance Registry System: N-[2-[Bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-4-thiazolecarboxamide hydrochloride(185104-11-4)

Safety Data

• Hazardous Substances Data: 185104-11-4(Hazardous Substances Data)

Usage

Description

Acotiamide Hydrochloride (YM-443, Z-338) is the hydrochloride salt form of acotiamide, a prokinetic agent with gastrointestinal (GI) motility-enhancing activity. It is a new orally active selective acetylcholinesterase inhibitor. Although the exact mechanism by which acotiamide exerts its effect has yet to be fully elucidated, this agent appears to inhibit acetylcholinesterase (AchE), an enzyme responsible for the breakdown of acetylcholine (Ach). Increased Ach concentrations lead to an improvement of gastric emptying and GI motility and eventually to a reduction of dyspepsia symptoms.

Uses

Acotiamide Hydrochloride is an acetylcholinesterase inhibitor which has been shown to stimulate gastric motility and improve gastric motility dysfunction in rats (1,2). Acotiamide Hydrochloride has also been shown to improve meal-related symptoms of functional dyspepsia.

Biological Activity

Acotiamide hydrochloride is an orally active, selective and reversible acetylcholinesterase (AChE) inhibitor, with an IC50 of 1.79 μM. Acotiamide hydrochloride can enhance gastric contractility and accelerate delayed gastric emptying. Acotiamide hydrochloride has the potential for the research of functional dyspepsia involving gastric motility dysfunction and intestinal inflammatory.

Upstream product

• 877997-99-4 2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-1,3-thiazole-4-carboxylic acid methyl ester 
• 121-05-1 N',N'-diisopropyl-ethane-1,2-diamine 
• 42833-66-9 2,4,5-trimethoxybenzoyl chloride 
• 490-64-2 asaronic acid 
• 28373-21-9 2-hydroxy-4,5-dimethoxybenzoic acid methyl ester 
• 610-90-2 2,4,5-trihydroxybenzoic acid 
• 61203-48-3 2-iodo-4,5-dimethoxybenzoic acid 
• 185106-16-5 Acotiamide 
• 877997-98-3 2-hydroxy-4,5-dimethoxybenzoic acid phenyl ester 
• 5722-93-0 2-hydroxy-4,5-dimethoxybenzoic acid 

Relevant articles and documents

Preparation method of acotiamide hydrochloride impurity

The invention discloses a preparation method of an acotiamide hydrochloride impurity. The method comprises the following steps: carrying out acylating chlorination on a raw material 2,4,5-trimethoxybenzoic acid to obtain 2,4,5-trimethoxybenzoyl chloride, and carrying out an amidation reaction on the 2,4,5-trimethoxybenzoyl chloride and 2-amino-4-ethoxycarbonyl-1,3-thiazole to obtain 2-amino-4-ethoxycarbonyl-1,3-thiazole (intermediate 1); hydrolyzing the intermediate 1 with sodium hydroxide to obtain 2-[N-(2,4,5-trimethoxybenzoyl)amino]-4-carboxyl-1,3-thiazole (intermediate 2); and performing an acylating chlorination reaction on the intermediate 2 to obtain an acyl chloride group, performing an amidation reaction on the acyl chloride group and N,N-diisopropylethylenediamine to obtain N-[2-(diisopropylamino)ethyl]-2-[(2,4,5-trimethoxybenzoyl)amino]-4-thiazole formamide (acotiamide), and performing a salt forming reaction on the acotiamide to obtain acotiamide hydrochloride. The preparation method of the acotiamide hydrochloride impurity has the advantages of mild reaction conditions, simple operation, low cost and high yield, and is suitable for industrial production.

IMPROVED METHOD FOR MANUFACTURING ACOTIAMIDE

PROBLEM TO BE SOLVED: To provide a method for manufacturing acotiamide or acotiamide hydrochloride trihydrate capable of avoiding the use of 2,4,5-trimethoxy benzoyl chloride that is an intermediate manufactured by using thionyl chloride. SOLUTION: There is provided a method for manufacturing acotiamide or acotiamide hydrochloride trihydrate comprising the steps of: manufacturing 2-[(2,4,5-trimethoxy benzoyl) amino]-1,3-thiazole-4-ethyl carboxylate from 2,4,5-trimethoxy benzoic acid S- (benzothiazole-2-yl) and 2-amino-1,3-thiazole-4-ethyl carboxylate; manufacturing 2-[(2-hydroxy-4,5-dimethoxy benzoyl) amino]-1,3-thiazole-4-ethyl carboxylate by demethylation; and reacting the resultant product with N,N-diisopropyl ethylenediamine to manufacture acotiamide. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

Acotiamide hydrochloride preparation method

The invention discloses an acotiamide hydrochloride preparation method. The acotiamide hydrochloride preparation method includes: taking 2,4,5-trihydroxybenzoic acid as a raw material easy to obtain, subjecting methyl iodide to selective methylation react