Penehyclidine quaternary ammonium salt and its derivative

A technology of penehyclidine and quaternary ammonium salt is applied in the field of anticholinergic compounds and their preparation, and can solve the problems of heart rate influence, inability to take long-term medication, senile dementia and the like

Inactive Publication Date: 2007-04-25
刘丽娅
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Penehyclidine hydrochloride, which is used as an anticholinergic drug to treat organophosphate poisoning, can also be used to treat diseases such as peripheral cholinergic hyperactivity, to improve microcirculation, relax visceral smooth muscle, and treat shock, chronic obstructive pulmonary disease (COPD) , visceral spasm, but because it can pass through the blood-brain barrier, it is very easy to cause adverse reactions in the central nervous system for COPD elderly patients who need long-term drug treatment, especially in my country. Reduced acetylcholine, such as long-term use of anticholinergic drugs that can penetrate the blood-brain barrier, may cause Alzheimer's disease
However, other traditional anticholinergic drugs such as atropine and scopolamine cannot pass through the blood-brain barrier, but they have a greater impact on heart rate, and they cannot be used for a long time. Therefore, although they can improve microcirculation and dilate bronchial smooth muscle, they cannot be used in patients with chronic diseases.

Method used

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  • Penehyclidine quaternary ammonium salt and its derivative
  • Penehyclidine quaternary ammonium salt and its derivative
  • Penehyclidine quaternary ammonium salt and its derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: Methyl penehyclidine quaternary ammonium iodide salt

[0037] The preparation method of methyl penehyclidine quaternary ammonium iodide salt:

[0038] The raw material penehyclidine and excess CH 3 1, add in the reaction bottle, then add acetonitrile and make raw material dissolve, then stir, reflux reaction 7-10 days, thin-layer chromatography monitors until reaction reaches equilibrium; Cool to room temperature, distill off solvent, residue is cleaned with ethyl acetate 2 -3 times, the target compound was obtained by ethanol recrystallization, and the measured yield was more than 50%.

[0039] After proton nuclear magnetic resonance verification, see attached drawings 1-1 to 1-2 (continuous spectrum of proton nuclear magnetic resonance spectrum), this structure is methyl penehyclidine quaternary ammonium iodide salt.

[0040] Pharmacodynamic experiments have proved that methyl penehyclidine quaternary ammonium iodide salt cannot enter the blood-brain b...

Embodiment 2

[0041] Embodiment 2: Isopropyl penehyclidine quaternary ammonium iodide salt

[0042] The preparation method of isopropyl penehyclidine quaternary ammonium iodide:

[0043] The raw material penehyclidine and excess CH 3 CH I CH 3 , add in the reaction bottle, then add acetonitrile to dissolve the raw material, then stir, reflux for 3-7 days, monitor by thin-layer chromatography until the reaction reaches equilibrium; cool to room temperature, evaporate the solvent, and wash the residue with ethyl acetate for 2- The target compound was obtained by ethanol recrystallization three times, and the measured yield was more than 50%.

[0044] Verified by H NMR spectroscopy, the structure is isopropyl penehyclidine quaternary ammonium iodide salt.

[0045] Pharmacodynamic experiments have proved that penehyclidine quaternary ammonium iodide salt cannot enter the blood-brain barrier, has no anti-tremor effect, but has anti-salivation effect, has no effect on the central nervous system,...

Embodiment 3

[0046] Embodiment 3: Ethyl penehyclidine quaternary ammonium hydrochloride

[0047] The preparation method of ethyl penehyclidine quaternary ammonium hydrochloride:

[0048] The raw material penehyclidine and excess CH 3 CH 2 Cl, add in the reaction flask, then add acetonitrile to dissolve the raw material, then stir, reflux reaction for 5-7 days, thin-layer chromatography monitoring until the reaction reaches equilibrium; evaporate the solvent, and the residue is washed 2-3 times with ethyl acetate, The target compound was obtained by recrystallization from ethanol, and the measured yield was more than 50%.

[0049] Verified by H NMR spectrum, the structure is ethyl penehyclidine quaternary ammonium hydrochloride.

[0050] Pharmacodynamic experiments have proved that penehyclidine quaternary ammonium hydrochloride cannot enter the blood-brain barrier, has no anti-tremor effect, but has anti-salivation effect, has no effect on the central nervous system, and is well tolerat...

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PUM

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Abstract

The invention discloses an ethyl ether quaternary ammonium salt and derivant as Choline-proof compound and preparing method with the following structure, wherein R is C1-C6 paraffin or substituted phenyl C1-C6 paraffin, which is methyl, phenylmethyl, ethyl group, propyl or isopropyl at best; M is halogen, which is F, Cl, Br or I at best. The invention can treat peripheral cholinergic nerve from exciting.

Description

technical field [0001] The present invention provides an anticholinergic compound and a preparation method thereof, specifically, penhyclidine (changtoning) quaternary ammonium salt and its derivatives, a preparation method thereof, and its use in the preparation and treatment of peripheral cholinergic hyperactivity application in medicines. Background technique [0002] Penehyclidine hydrochloride is a national first-class long-acting anticholinergic new drug independently developed and synthesized in China. Its English name is Penehyclidine Hydrochloride Injection and its chemical name is 3-(2-cyclopentyl-2-hydroxy-2-phenylethoxy Base) quinuclidine hydrochloride, the trade name is Chang Tuo Ning (long-acting Tuo Ning), used for the first aid treatment of organophosphorus poison (pesticide) poisoning and the maintenance of atropine in the later stage of poisoning or after aging of cholinesterase (ChE) (Atropineization refers to the critical state between the maximum physio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/08A61K31/439A61P39/02C07D221/00
Inventor 刘丽娅
Owner 刘丽娅
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