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

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...

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 antidepressants that are safe, fast-acting, and have few side effects, pharmacists have conducted various researches. try

[0004] Since the 1990s, some antidepressants with new mechanisms of action have appeared, such as NE / 5-HT reuptake inhibitor SNRI (Venlaxine, Milnacipran, Duloxetine, Nefazodone), selective monoamine oxidase inhibitor MAOI (Moclobemide, Toloxatone), selective NE reuptake inhibitor Uptake inhibitor NARI (Reboxetine), NE energy and specific 5-HT energy antidepressant NaSSa (Mirtazapine). Although these drugs have improved efficacy and rapid onset compared with SSRIs, they still have 1- 2-week lag period, so research on faster-acting drugs is urgent

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