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Optical-purity meptazinol orits salts, and preparing method

A technology of meprotamol and protamol, which is applied in the fields of organic chemistry, active ingredients of heterocyclic compounds, nervous system diseases, etc., and can solve problems such as the development and research of optically pure meprotamol.

Inactive Publication Date: 2006-10-25
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] There is a chiral carbon atom in the meptafol molecule, which can form a pair of optical enantiomers. The racemate of meptafol hydrochloride is used clinically. At present, there is no development of optically pure meptafol at home and abroad. Research

Method used

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  • Optical-purity meptazinol orits salts, and preparing method
  • Optical-purity meptazinol orits salts, and preparing method
  • Optical-purity meptazinol orits salts, and preparing method

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Example 1 Resolution of Mebutamol with Optically Pure Dibenzoyl Tartaric Acid

[0024] 10 grams of meprotamol racemate (preparable by the method disclosed in US Patent No. 4197239), 300 ml of absolute ethanol, and reflux to dissolve. Add 15.36 g of L-dibenzoyl tartaric acid / 50 ml of absolute ethanol solution dropwise, and add 600 ml of ethyl acetate after reflux for 1 hour, and 11.35 g of white solid is precipitated, and white crystals are obtained after recrystallization from methanol, namely (-)-Mepro Hephenol-L-dibenzoyl tartrate, melting point 171~173℃, [α] D -96.29°(c=0.105, MeOH), the white crystals were basified with sodium carbonate solution, extracted with ether, concentrated to obtain (-)-mebutamol 2.80g, and then salted with hydrogen chloride in ethanol solution to obtain (-) - Mebutamol hydrochloride 2.97g, melting point 214-5°C, [α] D -10.72° (c=0.167, H 2 O), e.e.=99.06%, based on Mebutamol, the total yield is 25.7%.

[0025] Split the mother liquor an...

Embodiment 2

[0027] Example 2 Single crystal X-ray diffraction test of (-)-mabutaol-L-dibenzoyl tartrate

[0028] (1) Instrument model: DIFFACTIS 586 X-ray four-circle diffractometer

[0029] (2) Computer and software package: SHELXS97 and SHELXL97 / 2 programs

[0030] (3) Single crystal preparation:

[0031] The (-)-meprotamol-L-dibenzoyl tartrate obtained in the examples was obtained by recrystallization from methanol.

[0032] (4) Experimental test:

[0033] Select a single crystal of 0.15mm × 0.15mm × 0.10mm, measure the unit cell parameters with the DIFFACTIS 586 X-ray four-circle diffractometer produced by Enraf-Nonius at room temperature, and collect the diffraction data, and use MoKα radiation (λ = 0.071073nm), in the range of 1.72°2σ(I)]. All intensity data are corrected by LP factor, the structure is solved by direct method, and all non-hydrogen atom coordinates are obtained by difference Fourier synthesis method. Deviation factor R=0.0673, R W2=0.1511, S=0.732, the absolute...

Embodiment 3

[0037] The mensuration of embodiment 3 optical purity

[0038] The instrument uses Agilent capillary electrophoresis system. Use 72cm×50μm uncoated quartz capillary, 30mmol / L phosphate buffer solution (pH8.05, containing 0.5% TM-β-CD, acetonitrile 12%), operating voltage 20kV, capillary column temperature 20℃, pressure injection 3kPa ×3s, detection wavelength 200nm. Baseline separation of the enantiomers of mebutamol was achieved under the selected experimental conditions. In the concentration range of 0.01-0.50mg / mL for the two enantiomers, the response of the concentration and the peak area showed a good linear relationship. The RSD of migration time is within 3%, the RSD of peak area is within 10%, and the minimum detection concentration is 0.01mg / mL. The optical purity of dibenzoyl tartrate meprotamol dextrorotary body, di-p-toluoyl tartrate meprotamol dextrorotary body, meprotamol hydrochloride dextrorotary body and left-handed body were 99.63%, 99.63%, respectively. ...

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Abstract

This invention belongs to pharmacy field, it relates optical pure mei pu ta fen and its preparation method and application. Racemation mei pu ta fen is splited by optical pure tartaric acid evolving object to get optical pure monomer, enantiomeric excess testing is done through capillary electrophoresis method, their e.e.valude are both excess 99 percent. Laevorotation and dextrorotation mei put a fen absolute configuration is decided by single crystal X-diffraction method as S and R. the R(+)mei pu ta fen has srong activity in analgesia activity testing, but S(-)mei pu ta fen has more stronger activity in acetylcholine esterase restrain activity testing, analgesic medicine and senile dementia medicine can be further prepared.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to optically pure R-(+)-meprotamol and S-(-)-meprotamol or their salts, and a preparation method thereof. Background technique [0002] Meptazinol, molecular formula C 15 h 23 NO, whose chemical name is 3-(3-ethyl-1-methyl-1H-hexahydroazepine-3-yl)phenol, is an analgesic drug listed in 1986, and its analgesic activity is similar to that of pentazocine Compared with other opioid analgesics, its side effects such as respiratory depression and addiction are extremely low, so it does not belong to the management category of "narcotics". It is known that meptafol can be applied to acute and chronic pain, such as trauma, postoperative, obstetric and cancer pain, etc. It is especially safe and effective for labor analgesia, and does not affect the health of newborns. The clinical curative effect after listing is reliable, and it was recorded in the British Pharmacopoeia in 1998. [0003] There is...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D223/04A61K31/55A61P25/28
Inventor 仇缀百章承继陈燕卢美艳谢琼
Owner FUDAN UNIV
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