Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use

An arylpiperazine and compound technology, applied in the field of medicinal chemistry, can solve the problems of lag effect, nausea, anxiety, insomnia, research urgency, etc., and achieve the effects of easy operation and simple preparation process

Inactive Publication Date: 2006-10-11
TIANJIN UNIV
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  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Tricyclic antidepressants (TCA, Anticholinergic) appeared in the 1950s, and 5-HT selective reuptake inhibitors SSRIs (Fluoxetine, Paroxetine, Sertaline, Citalopram, Fluvoxamine) appeared in the 1980s because of their good antidepressant properties, It has gradually replaced TCA and has become the leading product in the antidepressant market. However, because SSRI indirectly acts on all 5-HT receptors, it has side effects such as nausea, anxiety, insomnia, and sexual dysfunction. The weakness is the hysteresis effect, that is, the antidepressant effect usually appears after the first 2-6 weeks after starting to take the medicine. Therefore, in order to find a

Method used

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  • Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use
  • Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use
  • Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Example 1: 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-1-propane Alcohol synthesis

[0024] (1) 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-1-propanone

[0025]3-propionylbenzo[b]thiophene (0.57g, 3mmol), paraformaldehyde (0.18g, 6mmol), 2-methoxyphenylpiperazine hydrochloride (0.684g, 3mmol) in ethanol ( 10mL) solution under reflux for 24h. Water (30 mL) was added to the mixture, 10% sodium hydroxide was added to adjust the pH to 8.5, extracted with dichloromethane (30 mL×3), washed with water (50 mL×3), dried (anhydrous sodium sulfate), and the solvent was distilled off under reduced pressure to obtain Pale yellow oil (0.248g, 21%).

[0026] (2) 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-1-propanol

[0027] 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-1-propanone (0.248g , 0.63mmol) was dissolved in absolute ethanol (10mL), sodium borohydride (0.024...

Embodiment 2

[0029] Example 2: 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(3-trifluoromethylphenyl)piperazin-1-yl]-1- Synthesis of propanol

[0030] (1) 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(3-trifluoromethylphenyl)piperazin-1-yl]-1-propanone

[0031] 3-propionylbenzo[b]thiophene (0.57g, 3mmol), paraformaldehyde (0.18g, 6mmol), 2-3-trifluoromethylphenylpiperazine hydrochloride (0.8g, 3mmol) A solution of ethanol (10 mL) was refluxed for 30 h. Water (30 mL) was added to the mixture, 10% sodium hydroxide was added to adjust the pH to 8.5, extracted with dichloromethane (30 mL×3), washed with water (50 mL×3), dried (anhydrous sodium sulfate), and the solvent was distilled off under reduced pressure to obtain Pale yellow oil, the product was directly used in the next step without purification.

[0032] (2) 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(3-trifluoromethylphenyl)piperazin-1-yl]-1-propane alcohol

[0033] Dissolve the oil in the previous step in absolute ethanol (10 mL), add sodium...

Embodiment 3

[0035] Example 3: 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2,3-dichlorophenyl)piperazin-1-yl]-1- Synthesis of propanol

[0036] (1) 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2,3-dichlorophenyl)piperazin-1-yl]-1-propanone

[0037] 3-propionylbenzo[b]thiophene (0.57g, 3mmol), paraformaldehyde (0.18g, 6mmol), 2,3-dichlorophenylpiperazine hydrochloride (0.8g, 3mmol) in ethanol (10 mL) solution was reacted under reflux for 35 h. Water (30 mL) was added to the mixture, 10% sodium hydroxide was added to adjust the pH to 8.5, extracted with dichloromethane (30 mL×3), washed with water (50 mL×3), dried (anhydrous sodium sulfate), and the solvent was distilled off under reduced pressure to obtain Light yellow oil, the product was directly used in the next reaction without purification.

[0038] (2) 1-(Benzo[b]thiophen-3-yl)-2-methyl-3-[4-(2,3-dichlorophenyl)piperazin-1-yl]-1-propane alcohol

[0039] Dissolve the oil in the previous step in absolute ethanol (10 mL), add sodium borohy...

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Abstract

This invention belongin to medicinal chemistry, pubilize the structure and synthesis of aryl-diethylenediamine modified benzo[b]thiophenes with antidepressant function. Its structure is depicted as picuture. Ar structure is as depicted.the synthesis of the compound is as followings: mix 1M 3-propionyl benzo[b]thiophenes,1-5M cavaform and 1-5M aryl-piperazidine hydrochlorate in 1-50 weight folds ethanol, inverse flowing react 1-80 hours, obtain 1-( benzo[b]thiophenes-3)-2- methyl-3-( 4-aryl-piperazidine-)1- acetone; Mix 1M 1-( benzo[b]thiophenes-3)-2- methyl-3-( 4-aryl-piperazidine-)1- acetone and 0.2-5M sodium borohydride in 1-50 weight folds of ethanol, react at 0-100deg C for 1-20, 1-( benzo[b]thiophenes-3)-2- methyl-3-( 4-aryl-piperazidine-)1- propanol obtained. This kind of compounds could be used for antidepressant drug preparation in the form of free alkali or salt. This invention is advantageous in simplied preparation and easy manipulation.

Description

technical field [0001] The invention relates to the structure, preparation method and application of an arylpiperazine-modified benzo[b]thiophene compound with antidepressant activity, and belongs to the field of medicinal chemistry. Background technique [0002] Depression is a common mental illness, which is an emotional disorder. As the pace of life continues to accelerate, people's mental pressure is gradually increasing. Depression has become a common disease in modern society, with a high incidence, and its incidence is rising rapidly. : According to incomplete statistics, at present the world's depression patients have accounted for 3%-5% of the world's population, almost seen in all ages, and its prevalence is about 3% in the general population, and the patient population in general hospital health services In patients with chronic physical diseases (such as cardiovascular disease, diabetes), the rate of depressive disorder can be as high as 20%, but only a very smal...

Claims

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Application Information

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IPC IPC(8): C07D409/08C07D409/14C07D241/04A61K31/381A61K31/496A61P25/24
Inventor 李爱军刘东志周雪琴
Owner TIANJIN UNIV
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