Spermidine alkaloid compound as well as preparation method, pharmaceutical composition and application thereof

A technology of alkaloids and compounds, applied in the field of medicine, can solve problems such as aggravation, acceleration of cognitive dysfunction, occurrence, etc., and achieve obvious inhibitory effect.

Pending Publication Date: 2022-05-06
CHINA JAPAN FRIENDSHIP HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When β-secretase-1 (BACE1) and γ-secretase work together to cut amyloid precursor (APP), APP will be degraded, resulting in the increase of Aβ and aggregation to form amyloid plaques, which will accelerate cognitive dysfunction and cause Onset or exacerbation of AD

Method used

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  • Spermidine alkaloid compound as well as preparation method, pharmaceutical composition and application thereof
  • Spermidine alkaloid compound as well as preparation method, pharmaceutical composition and application thereof
  • Spermidine alkaloid compound as well as preparation method, pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] The embodiment of the present invention provides a preparation method of daturaspermidines C-G, comprising the following steps:

[0065] Step S10, take the dried daphnia flowers, add 10-20 times the weight of the extraction solvent, reflux extraction at 65-85°C for 1-3 hours, repeat 2-4 times, combine the extracts, filter, and concentrate under reduced pressure to obtain concentrated liquid, wherein the extraction solvent is at least one of water, methanol and ethanol, preferably 60-95v% ethanol aqueous solution;

[0066] Step S11, sequentially using petroleum ether, dichloromethane and ethyl acetate as organic solvents to extract the concentrated solution (respectively repeat the extraction 2-5 times, and combine the organic phases), and recover the organic solvents to obtain the extracts, wherein the organic solvent The volume of the added amount is 1.5-2 times the volume of the concentrate;

[0067] Step S12, performing silica gel column chromatography on the extrac...

Embodiment 2

[0074] The embodiment of the present invention provides daturaspermidines C, its molecular formula is as follows:

[0075]

[0076] The physical properties and NMR data of daturaspermidine C are as follows:

[0077] Yellow amorphous powder; UV(MeOH)λ max 205,280nm; IR(KBr)ν max 3403,1652cm –1 ;HR-ESI-MS: m / z 480.2469[M+H] + (cal. 480. 2493); 1 H NMR (600MHz, CD 3 OD): δ H 3.09(1H,m,H-2α),3.18(1H,m,H-2β),1.79(1H,m,H-3α),1.63(1H,m,H-3β),3.43(1H,m, H-4α), 3.65(1H,t,J=9.5Hz,H-4β),3.32(2H,m,H-6),1.66(1H,m,H-7α),1.48(1H,m,H -7β),1.42(1H,m,H-8α),1.58(1H,m,H-8β),3.34(1H,m,H-9α),3.34(1H,m,H-9β),1.93( 3H,s,H-12),7.21(1H,d,J=8.7Hz,H-2'),6.71(1H,m,H-3'),6.71(1H,m,H-5'), 7.21(1H,d,J=8.8Hz,H-6'),6.57(1H,d,J=12.6Hz,H-7'),5.94(1H,d,J=12.6Hz,H-8') ,7.39(1H,m,H-2”),6.78(1H,d,J=8.6Hz,H-3”),6.77(1H,d,J=8.6Hz,H-5”),7.39(1H ,m,H-6"),7.45(1H,d,J=15.7Hz,H-7"),6.34(1H,d,J=15.7Hz,H-8"); 13 C NMR (150MHz, CD 3 OD): δ c37.9 / 38.2(C-2), 28.1 / 29.5(C-3), 44.0 / 47.7(C-4), 46.0 / 49.7(C-6), 25...

Embodiment 3

[0079] The embodiment of the present invention provides daturaspermidine D, its molecular formula is as follows:

[0080]

[0081] The physical properties and NMR data of daturaspermidine D are as follows:

[0082] Yellow amorphous powder; UV(MeOH)λ max 204,274nm; IR(KBr)ν max 3403,1652cm –1 ;HR-ESI-MS: m / z 480.2478[M+H] + (cal. 480. 2493); 1 H NMR (500MHz, CD 3 OD): δ H 3.05(1H,t,J=6.8Hz,H-2α),3.19(1H,t,J=6.9Hz,H-2β),1.79(1H,m,H-3α),1.63(1H,m,H -3β),3.41(1H,m,H-4α),3.65(1H,t,J=9.5Hz,H-4β),3.29(2H,m,H-6),1.69(1H,m,H- 7α),1.41(1H,m,H-7β),1.52(1H,m,H-8α),1.38(1H,m,H-8β),3.13(1H,t,J=6.5Hz,H-9α ), 3.27(1H,t,J=6.7Hz,H-9β),1.95(3H,s,H-12),7.23(1H,s,H-2'),6.72(1H,m,H-3 '),6.72(1H,m,H-5'),7.22(1H,s,H-6'),6.58(1H,d,J=12.6Hz,H-7'),5.93(1H,d, J=12.6Hz, H-8'),7.39(1H,d,J=3.9Hz,H-2"),6.72(1H,m H-3"),6.72(1H,m,H-5") ,7.38(1H,d,J=4.0Hz,H-6”),6.62(1H,d,J=12.6Hz,H-7”),5.79(1H,d,J=12.6Hz,H-8” ); 13 C NMR (125MHz, CD 3 OD): δ c 37.8 / 38.2(C-2), 28.1 / 29.5(C-3), 43.9 / 47.7(C-4),...

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Abstract

The invention discloses a spermidine alkaloid compound as well as a preparation method, a pharmaceutical composition and application thereof, and particularly discloses application of the spermidine alkaloid compound in preparation of medicines for preventing or treating Alzheimer's disease. Pharmacological experiment results show that the compound has good BACE1 inhibitory activity, the inhibitory effect of the compound is superior to that of a positive drug donepezil, and the compound can be used as a drug for treating Alzheimer's disease.

Description

technical field [0001] The invention belongs to the technical field of medicine, and more specifically relates to a spermidine alkaloid compound and its preparation method, pharmaceutical composition and application. Background technique [0002] Alzheimer's disease (AD) is a degenerative disease of the central nervous system, commonly manifested as progressive cognitive and behavioral impairment in the elderly, and its incidence increases with age. With the development of the global population aging process, the number of AD patients is also showing an upward trend; the pathogenesis of AD is complex, and currently marketed drugs can only slow down the course of the disease and relieve symptoms, but cannot ultimately reverse the course of the disease and cure the disease. [0003] β-amyloid protein (β-Amyloidprotein, Aβ), the main component that causes the characteristic pathological changes in the brain of AD patients, is a neurotoxic substance that can cause neuronal damag...

Claims

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Application Information

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IPC IPC(8): C07C235/34C07C231/24A61P25/28A61K31/165
CPCC07C235/34A61P25/28
Inventor张维库续洁琨赫军张佳李雅楠王玉伟
OwnerCHINA JAPAN FRIENDSHIP HOSPITAL