Substituted arylpiperazine aryl alkanone derivatives and their application in the preparation of analgesic drugs

A technology of arylpiperazine and aralkylone, which is applied in the field of arylpiperazine aralkylone compounds, can solve problems such as reduction of gastric peristalsis, and achieve the effect of strong analgesic effect and strong anti-pain writhing reaction effect.

Active Publication Date: 2015-12-16
NHWA PHARMA CORPORATION +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] One of the technical problems to be solved in the present invention is to disclose a class of substituted arylpiperazine aryl alkanone derivatives to overcome the defects of existing drugs that have side effects such as addiction, respiratory depression, and gastric motility reduction, so as to solve clinical problems

Method used

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  • Substituted arylpiperazine aryl alkanone derivatives and their application in the preparation of analgesic drugs
  • Substituted arylpiperazine aryl alkanone derivatives and their application in the preparation of analgesic drugs
  • Substituted arylpiperazine aryl alkanone derivatives and their application in the preparation of analgesic drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] 1-(pyridin-2-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethanone (I-1) hydrochloride, hydrobromide and Sulfate preparation

[0082] 1) Intermediate: Synthesis of 2-bromo-1-(pyridin-2-yl)ethanone hydrobromide

[0083] 1-(pyridin-2-yl)ethanone (6.00g, 0.05mol) was added in 55ml of glacial acetic acid, then bromine (8.80g, 0.055mol) and 40% hydrobromic acid (10.20g, 0.05mol), heated up to 75°C for 3.0h, stopped heating, cooled in an ice-water bath, filtered, and recrystallized with a mixed solvent of ethyl acetate and methanol (weight ratio 5:1) to obtain white solid 2-bromo-1-( Pyridin-2-yl)ethanone hydrobromide 12.4g, yield 88.2%.

[0084] ESI-MS[M+H]+: m / z199.96

[0085] 2) Synthesis of 1-(pyridin-2-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethanone (I-1) hydrochloride

[0086] m-Trifluoromethylphenylpiperazine hydrochloride (2.67g, 0.01mol), 2-bromo-1-(pyridin-2-yl)ethanone hydrobromide (2.81g, 0.011mol) and anhydrous Potassium carbonate (5.52g, 0...

Embodiment 2

[0098] Preparation of 1-(pyridin-3-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethanone (I-2) hydrochloride 1) intermediate : Synthesis of 2-bromo-1-(pyridin-3-yl)ethanone hydrobromide

[0099] 1-(pyridin-3-yl)ethanone (6.00g, 0.05mol) was added in 55ml of glacial acetic acid, then bromine (8.80g, 0.055mol) and 40% hydrobromic acid (10.20g, 0.05mol), heated to 75°C for 3.0h, stopped heating, cooled in an ice-water bath, filtered, and recrystallized with a mixed solvent of ethyl acetate and methanol (5:1 by weight) to obtain off-white solid 2-bromo-1- (Pyridin-3-yl)ethanone hydrobromide 13.1 g, yield 93.2%.

[0100] ESI-MS[M+H]+: m / z199.96

[0101] 2) Synthesis of 1-(pyridin-3-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethanone (I-2) hydrochloride

[0102] m-Trifluoromethylphenylpiperazine hydrochloride (2.67g, 0.01mol), 2-bromo-1-(pyridin-3-yl)ethanone hydrobromide (2.81g, 0.011mol) and anhydrous Potassium carbonate (5.52g, 0.04mol) was added into 30ml of DM...

Embodiment 3

[0107] Preparation of 1-(pyridin-4-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethanone (I-3)hydrochloride

[0108] 1) Intermediate: Synthesis of 2-bromo-1-(pyridin-4-yl)ethanone hydrobromide

[0109] 1-(pyridin-3-yl)ethanone (2.42g, 0.02mol) was added in 25ml of glacial acetic acid, then bromine (3.52g, 0.022mol) and 40% hydrobromic acid (4.08g, 0.02mol), heated to 75 ° C for 3.0 h, stopped heating, cooled in an ice-water bath, filtered, and recrystallized with a mixed solvent of ethyl acetate and methanol (5:1 by weight) to obtain off-white solid 2-bromo-1- (Pyridin-4-yl)ethanone hydrobromide 4.04g, yield 71.9%.

[0110] ESI-MS[M+H] + : m / z199.98

[0111] 2) Synthesis of 1-(pyridin-4-yl)-2-(4-(3-(trifluoromethyl)phenyl)piperazin-1-yl)ethanone (I-3) hydrochloride

[0112] m-Trifluoromethylphenylpiperazine hydrochloride (2.67g, 0.01mol), 2-bromo-1-(pyridin-4-yl)ethanone hydrobromide (2.81g, 0.011mol) and anhydrous Potassium carbonate (5.52g, 0.04mol) was added into...

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Abstract

The invention discloses a substituted aryl piperazine aralkyl ketone derivative and an application of the derivative in preparing an analgesic. The substituted aryl piperazine aralkyl ketone derivative as well as physiologically acceptable salt thereof have quite a useful pharmaceutical property and excellent tolerance, particularly applied as a novel analgesic. The compound is a non-addictive central analgesic and free from remarkable sedation through animal experiments, and the compound is quite low in toxic and side effects and relatively high in a safety index. The substituted aryl piperazine aralkyl ketone derivative is free alkali or salt of a compound expressed as the structural general formula in the specification.

Description

technical field [0001] The invention relates to an arylpiperazine aryl alkanone compound and its application in the preparation of analgesic drugs. Background technique [0002] Severe acute and chronic pain refers to the excitation of nociceptors caused by various injurious stimuli, and the impulse of the messenger is transmitted through nociceptive information, which is transmitted to the central nervous system to cause nociception and pain. Severe acute and chronic pain, including tumor pain, postoperative pain, and various recurrent acute and chronic pains, plagues tens of millions of patients and is a major clinical problem at present. [0003] Clinically used analgesics can be roughly divided into the following three categories: 1) Non-steroidal anti-inflammatory analgesics 2) Opioid analgesics 3) Other non-opioid analgesics, including: local anesthetics, antidepressants , antiepileptic drugs, etc. [0004] Currently, opioid analgesics are mainly used clinically for ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/50C07D213/74C07D239/26A61K31/496A61K31/506A61P25/04A61P29/02
Inventor 李建其王冠张桂森徐祥清张莉刘世成赵松于民权
Owner NHWA PHARMA CORPORATION
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