4-[2-(artyl sulfo) benzyl]-1-derivative of aryl-piperazine, preparation method and application

A technology of arylpiperazine and derivatives, applied in the field of 4-[2-(arylthio)benzyl]-1-arylpiperazine derivatives and their preparation and application, can solve nausea, anxiety, Insomnia, research urgency, hysteresis effect and other problems, to achieve the effect of no high temperature and high pressure operation, simple preparation process and high yield

Inactive Publication Date: 2005-11-16
TIANJIN UNIV
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  • Summary
  • Abstract
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  • Claims
  • Application Information

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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, Nefezodone), selective monoamine oxidase inhibitor MAOI (Moclobe mide, Toloxatone), selective NE Reuptake 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, but there are still 1 -2-week lag period, so research on faster-acting drugs is urgent

Method used

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  • 4-[2-(artyl sulfo) benzyl]-1-derivative of aryl-piperazine, preparation method and application
  • 4-[2-(artyl sulfo) benzyl]-1-derivative of aryl-piperazine, preparation method and application
  • 4-[2-(artyl sulfo) benzyl]-1-derivative of aryl-piperazine, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: 4-[2-(2-methoxyphenylthio)benzyl]-1-(3-trifluoromethylphenyl)piperazine hydrochloride

[0025] Step 1: 2-(2-methoxyphenylthio)benzoic acid

[0026] In the mixture of o-methoxythiophenol (48mmol, 6.72g) and DMF (120ml), add anhydrous potassium carbonate (144mmol, 19.9g), copper powder (12.6mmol, 0.8g), o-chlorobenzoic acid ( 40mmol, 6.26g), the reaction mixture was warmed up to 100°C and stirred vigorously for 24h, cooled, 600ml of distilled water was added to the mixture, filtered, the filtrate was decolorized with activated carbon for 30min, filtered, the filtrate was adjusted to pH 7.0 with 6mol / L hydrochloric acid, filtered, and the filtrate was adjusted to pH3 .0, white crystals were precipitated, filtered, washed with water (20ml×3), and vacuum-dried to obtain white crystals (7.85g, 75.5%).

[0027] mp: 198.0~200.0℃. 1 H-NMR (CDCl 3 )δ: 8.14(d, 1H), 7.58(d, 2H), 7.57(t, 1H), 7.28(m, 2H), 7.17(t, 3H), 7.04(m, 2H), 6.82(d, 2H ), 3.80(s, 3H). 13 H-NMRδ...

Embodiment 2

[0037] Example 2: 4-[2-(2-methoxyphenylthio)benzyl]-1-(3-chlorophenyl)piperazine hydrochloride

[0038] Step 1, Step 2, and Step 3 of this embodiment are the same as those of Embodiment 1.

[0039] Step 4: 4-[2-(2-methoxyphenylthio)benzyl]-1-(3-chlorophenyl)piperazine hydrochloride

[0040] 2-(2-Methoxyphenylthio)benzyl chloride (0.004226mol, 1.04g) was dissolved in DMF (50ml), triethylamine (0.005071mol, 0.71ml) was added, a catalytic amount of anhydrous sodium iodide was added, 1-(3-Chlorophenyl)piperazine (0.004649mol, 0.9144g), heated up at 80°C for 6.5h, cooled the reaction solution to room temperature, added water (100ml), extracted with chloroform (50ml×3), washed with water (50ml× 10), dried in chloroform (anhydrous sodium sulfate), filtered through silica gel, and evaporated the solvent under reduced pressure to obtain a light yellow oil, which was dissolved in anhydrous ether (60ml), added dropwise with ether hydrochloride solution, and a white solid was precipitate...

Embodiment 3

[0042] Example 3: 4-[2-(2-methoxyphenylthio)benzyl]-1-phenylpiperazine hydrochloride

[0043] Step 1, Step 2, and Step 3 of this embodiment are the same as those of Embodiment 1.

[0044] Step 4: 4-[2-(2-methoxyphenylthio)benzyl]-1-phenylpiperazine hydrochloride

[0045]2-(2-Methoxyphenylthio)benzyl chloride (0.002mol, 0.5g) was dissolved in DMF (50ml), triethylamine (0.0023mol, 0.32ml) was added, a catalytic amount of anhydrous sodium iodide was added, and 1-Phenylpiperazine (0.0022mol, 0.357g), heat up to 80°C for 7.5h, cool the reaction solution to room temperature, add water (100ml), extract with chloroform (50ml×3), wash with water (50ml×10), chloroform solution Dry (anhydrous sodium sulfate), filter through silica gel, evaporate the solvent under reduced pressure to obtain light yellow oil, dissolve it in anhydrous diethyl ether (60ml), add diethyl hydrochloride solution dropwise, precipitate a white solid, filter, decompress Drying gave a white solid (0.214 g, 22.5%)....

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Abstract

An anti-depression 4-[2-(arylthio) benzyl]-1-arylpiperazine derivative used to prepare the medicine for treating depression is prepared through Ullmann reaction between p-methoxy benzeneethiol and p-chlorobenzoic acid to generate thioether, reducing, chlorinating and N-alkylation.

Description

technical field [0001] The invention relates to the structure, preparation method and application of a 4-[2-(arylthio)benzyl]-1-arylpiperazine derivative with antidepressant activity, and the technology 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% to 5% of the world's population, almost seen in all ages, and its prevalence is about 3% in the general population. 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 small proportion of patients have been identified....

Claims

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Application Information

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IPC IPC(8): C07D295/096
Inventor 李爱军刘东志周雪琴
Owner TIANJIN UNIV
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