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Acetylcholin esterase inhibitor lignanolide compound and preparation method and application thereof

An acetylcholinesterase and inhibitor technology, which is applied in the directions of drug combinations, pharmaceutical formulations, and medical preparations containing active ingredients, and can solve the problems of restricted application and low oral bioavailability.

Inactive Publication Date: 2016-05-04
JILIN AGRICULTURAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its oral bioavailability is low, which seriously restricts its clinical application.

Method used

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  • Acetylcholin esterase inhibitor lignanolide compound and preparation method and application thereof
  • Acetylcholin esterase inhibitor lignanolide compound and preparation method and application thereof
  • Acetylcholin esterase inhibitor lignanolide compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0012] Example 14-(4-(3,4-dimethoxybenzyl)-2-carbonyl)tetrahydrofuranmethyl-2-methoxyphenol 2-(N-tert-butoxycarbonyl)amino-4-methylthio Synthesis of alkyl butyrate (ARG1).

[0013] Weigh 0.20g (0.54mmol) arctigenin, 0.27g (1.08mmol) BOC-L-methionine, 0.21g (1.08mmol) 1-ethyl-(3-dimethylaminopropyl) carbodiimide Hydrochloride (EDCI), 0.03g (0.27mmol) 4-dimethylaminopyridine (DMAP) was placed in a 100ml spinner bottle, added 10ml of acetonitrile solution, stirred and dissolved in an ice-water bath, and reacted at room temperature for 1-2 hours, detected by TLC After the reaction was completed, the solvent was evaporated under reduced pressure to obtain a light yellow viscous substance. The viscous material was separated by column chromatography with YMC reversed-phase packing, eluted with acetonitrile / water (55:45) mixed solvent, the required components were collected, the organic solvent was evaporated under reduced pressure, and freeze-dried to obtain a white powder compound ...

Embodiment 2

[0015] Example 24-(4-(3,4-dimethoxybenzyl)-2-carbonyl)tetrahydrofuranmethyl-2-methoxyphenol-2-(N-tert-butoxycarbonyl)amino-3-( Synthesis of 2-indolyl)propionate (ARG2).

[0016] The preparation method is the same as in Example 1, except that Boc-tryptophan is used to obtain compound ARG2.

[0017]

[0018] White solid, 72% yield. 1 H-NMR (CDCl 3 ,300MHz)δ ppm :7.68(1H,d,7.8HZ,C 6 H 5 ),7.39(1H,dd,0.9,8.4HZ,C 6 H 5 ),7.25(1H,dd,0.9,7.2HZ,C 6 H 5 ),7.20(1H,dd,0.9,7.2HZ,C 6 H 5 ),7.14(1H,dd,0.9,8.4HZ,C 6 H 5 ),6.80(1H,d,8.1HZ,C 6 H 5 ),6.64(1H,dd,1.8,8.1HZ,C 6 H 5 ),6.75(1H,d,3.9HZ,C 6 H 5 ),6.84(1H,d,8.1HZ,C 6 H 5 ),6.56(1H,dd,2.1HZ,8.4HZ,C 6 H 5 ),6.51(1H,d,3.9HZ,C 6 H 5 ),5.16(N H ),4.97(m,-NH-C H -COO-),3.93,4.22(m,-COOC H 2 -),3.87(3H,s,OC H 3 ),3.82(3H,s,OC H 3 ),3.73(3H,s,OC H 3 ),3.56,3.45(m,C H 2 ),2.963.03(m,C H 2 ),2.70(m,C H ),2.54,2.63(m,C H 2 ),2.48(m,C H ),1.44(3H,s,C H 3 ).

Embodiment 3

[0019] Example 34-(4-(3,4-dimethoxybenzyl)-2-carbonyl)tetrahydrofuranmethyl-2-methoxyphenol-N-tert-butoxycarbonyl 2-tetrahydropyrrole carboxylate ( Synthesis of ARG3).

[0020] The preparation method is the same as in Example 1, except that Boc-L-proline is used to obtain compound ARG3.

[0021]

[0022] White solid, 65% yield. 1 H-NMR (CDCl 3 ,300MHz)δ ppm :7.04(1H,d,8.1HZ,C 6 H 5 ),6.94(1H,d,7.8HZ,C 6 H 5 ),6.77(1H,d,2.1HZ,C 6 H 5 ),6.70(1H,dd,1.8HZ,8.1HZ,C 6 H 5 ),6.59(1H,dd,1.2HZ,8.4HZ,C6 H 5 ),6.51(1H,d,2.1HZ,C 6 H 5 ),4.52(m,-NH-C H -COO-),3.93,4.16(m,-COOC H 2 -),3.87(3H,s,OC H 3 ),3.84(3H,s,OC H 3 ),3.77(3H,s,OC H 3 ),3.523.67(m,C H 2 ),2.973.00(m,C H 2 ),2.70(m,C H ),2.342.69(m,C H 2 ),2.30(m,C H ),2.16(m,C H 2 ),1.52,1.64(m,C H 2 ),1.49(3H,s,C H 3 ).

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Abstract

The invention relates to an acetylcholin esterase inhibitor lignanolide compound, a preparation method thereof and an application thereof as an acetylcholin esterase active inhibitor for improving the memory of patients with senile dementia. The acetylcholin esterase inhibitor lignanolide compound is shown as a general structural formula I, wherein R is a Boc-L-Met, Boc-L-Try, Boc-L-Pro, Boc-L-Phe, Boc-L-Thr amino-acid side chain.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to an acetylcholinesterase inhibitor-lignan lactone composition and a preparation method thereof and its use as an acetylcholinesterase activity inhibitor, as well as its application in improving the memory of senile dementia patients. Background technique [0002] Alzheimer's disease (AD) is a progressive neurodegenerative disease, which is mainly manifested as memory function decline and recognition impairment, accompanied by various neurological symptoms and behavioral disorders, and has a very high incidence rate. Currently, the market approves the treatment of AD Most of the drugs used to inhibit the activity of acetylcholinesterase mainly include tacrine, donepezil, carbamate, huperzine A, etc. With the arrival of the aging of the global population, the number of its incidence will continue to increase, and the demand for anti-senile dementia drugs will have broad...

Claims

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Application Information

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IPC IPC(8): C07D307/33A61K31/341A61P25/28
CPCC07D307/33
Inventor 蔡恩博杨利民郑曼玲韩梅宋明杰赵岩董蕊邸鹏宗颖陈秋连高小芮
Owner JILIN AGRICULTURAL UNIV