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4-hydroxycoumarin-3-Schiff base derivate and use thereof for curing Alzheimer's disease

A technology of hydroxycoumarin and Schiff base, applied in the direction of drug combination, active ingredients of heterocyclic compounds, nervous system diseases, etc., can solve the problem of inhibiting the pathological process of AD

Active Publication Date: 2015-11-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Drugs targeting a single target can only regulate one of the physiological pathways and cannot fundamentally inhibit the pathological process of AD

Method used

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  • 4-hydroxycoumarin-3-Schiff base derivate and use thereof for curing Alzheimer's disease
  • 4-hydroxycoumarin-3-Schiff base derivate and use thereof for curing Alzheimer's disease
  • 4-hydroxycoumarin-3-Schiff base derivate and use thereof for curing Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Preparation of intermediate 3-amino-4-hydroxycoumarin (1b)

[0058] 3.0g of raw material 3-nitro-4-hydroxycoumarin (1a) was dissolved in 200ml of absolute ethanol, and a catalytic amount of 10% Pt / C was added, and in H 2 Under the atmosphere, react at room temperature for 6-8 hours. After monitoring the reaction, remove Pt / C by suction filtration, and recrystallize from ethanol to obtain about 2.1 g of white solid 1b, with a yield of about 70%. m.p.220-222℃.1H NMR(500MHz,DMSO)δ8.27(s,2H),7.86(dd,J=7.9,1.5Hz,1H),7.52-7.45(m,1H),7.33-7.18(m ,2H).13C NMR(126MHz,DMSO)δ160.71,152.00,130.54,124.12,123.50,123.50,121.57,116.45,116.45.ESI-MS m / z:178.0[M+H]+.

Embodiment 2

[0060] Preparation of (E)-4-hydroxyl-3-((2,3-dihydroxybenzylidene)amino)-2-hydrogen-pyran-2-one (1)

[0061]Add 0.1g (0.56mmol) of 3-amino-4-hydroxycoumarin in a single-necked flask, dissolve it with an appropriate amount of absolute ethanol, then add about 0.08g (0.56mmol) of 2,3-dihydroxybenzaldehyde, dropwise After 3 drops of glacial acetic acid, stirred and reacted at room temperature for 5 hours, a yellow precipitate appeared, filtered with suction, washed with absolute ethanol three times, dried, and recrystallized from DMF / acetone (volume ratio: 3:1) to obtain 120 mg of a red solid. , yield 81%; m.p.>250℃, IR(KBr)ν3421,1606,1542,1461,1417,1228,1109,901,754,474cm -1 . 1 H NMR (500MHz, DMSO) δ16.23(s, 1H), 9.85(s, 1H), 7.95(d, J=7.7Hz, 1H), 7.50(t, J=7.6Hz, 1H), 7.24(dd ,J=14.2,7.6Hz,2H), 6.75(d,J=7.8Hz,1H),6.69(d,J=7.4Hz,1H),6.44(t,J=7.7Hz,1H).ESI-MS m / z:295.8[M-H] - ; HRMS (ESI) m / z 296.0562[M-H] - (calcd for 296.0564, C 16 h 10 NO 5 ).

Embodiment 3

[0063] Preparation of (E)-4-hydroxyl-3-((2,4-dihydroxybenzylidene)amino)-2-hydrogen-pyran-2-one (2)

[0064] The preparation process is the same as 1, the raw material salicylaldehyde is replaced by 2,4-dihydroxybenzaldehyde, the yield is 81%; yellow solid, m.p.>250℃, IR(KBr)ν3427,1619,1538,1392,1316,1234,1136, 1031,759,445cm -1 . 1 H NMR (500MHz, DMSO) δ12.79(s, 2H), 10.94(s, 1H), 9.80(s, 1H), 7.97(d, J=7.3Hz, 1H), 7.61(dd, J=18.6, 7.9 Hz,2H),7.40-7.29(m,3H),6.53(s,1H).ESI-MS m / z:295.9[M-H] - ; HRMS (ESI) m / z 296.0562[M-H] - (calcd for 296.0564, C 16 h 10 NO 5 ).

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Abstract

The invention relates to the field of medicinal chemistry, in particular to a 4-hydroxycoumarin-3-Schiff base compound (I). Pharmacodynamic experiments prove that the compound is a multifunctional monoamine oxidase (MAO) inhibitor, has better effects of inhibiting beta-amyloid protein (A beta) aggregation, metal ion chelation, oxidation resistance and neuroprotection, and can be used for curing Alzheimer's disease.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a class of 4-hydroxycoumarin-3-Schiff base compounds, which, as multifunctional monoamine oxidase (MAO) inhibitors, have better inhibition of β-amyloid (Aβ) aggregation, metal ion chelation, anti-oxidation and neuroprotection, can be used for the treatment of Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease in the elderly. The pathogenesis of AD is complex, and its causes are not only related to the decrease of choline level in the brain, but also related to the aggregation of Aβ, the disorder of metal ion metabolism, the disorder of calcium balance, the increase of reactive oxygen species (ROS) and the occurrence of inflammation, etc. factors are closely related. Although the pathological mechanism of Alzheimer's disease is not fully understood so far, several theories are recogn...

Claims

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Application Information

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IPC IPC(8): C07D311/12A61K31/37A61P25/28
CPCC07D311/12
Inventor 孔令义王小兵王志敏
Owner CHINA PHARM UNIV
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