Flavone derivative and application thereof

A technology of derivatives and flavones, applied in the field of multi-target, multi-action anti-Alzheimer's flavone derivatives and its preparation, can solve problems such as unsatisfactory effects

Active Publication Date: 2018-07-20
CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In view of the complexity of AD inducements, the traditional "single molecule, single target" drug design strategy is not ideal. Based on the strategy of "targeted multi-target ligands" (MTDLs) to find and discover AD target enzyme inhibitory activity, metal chelation Multi-target drugs or drug lead compounds with two or more complementary biological activities such as anti-oxidation and anti-oxidation may be an ideal approach for the design and discovery of AD therapeutic drugs

Method used

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  • Flavone derivative and application thereof
  • Flavone derivative and application thereof
  • Flavone derivative and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: the preparation of compound II-3c

[0034] Chemical reaction formula:

[0035]

[0036] Synthesis of intermediate e

[0037] Weigh anhydrous zinc chloride powder (10.0g, 73.3mmol) into anhydrous acetonitrile (30g, 0.73mol), heat to 60-70°C, stir vigorously until no zinc chloride particles, then add phloroglucinol ( 20g, 0.15mol), after stirring and dissolving, the reaction solution was cooled to 0-5°C. Anhydrous diethyl ether (100 mL) was added, and dry hydrogen chloride gas was passed through for 12 h until no solid was formed. The reaction solution was placed in a refrigerator at 4 °C overnight. Suction filtration, the filter cake was washed with anhydrous ether. The filter cake was transferred to a flask in situ, water (1 L) was added, and after boiling for 2 hours, it was filtered while it was still hot. After the filtrate was cooled overnight, crystals were precipitated, filtered, and dried to obtain the product with a yield of 75%. 1 HNMR (50...

Embodiment 2

[0052] Embodiment 2: the preparation of compound I-2c

[0053]

[0054] Synthesis of intermediate j

[0055]Take 2-hydroxy-4,6-dimethoxyacetophenone (19.6g, 0.1mol), iodine element (11.4g, 0.045mol), and ethanol (200mL) into the reaction flask in sequence, and stir thoroughly. Take another HIO 3 (2.6g, 0.015mol) was dissolved in water (5mL), added to the reaction solution, and stirred well at room temperature for about 2.5 hours. After TLC stirring, the raw material point disappeared. Stop stirring and filter with suction. After the filtrate was concentrated to 1 / 2 volume, it was cooled to stand still, then suction filtered, and the filter cakes were combined to obtain a white solid with a yield of 93%. MS(ESI):m / z[M+H] + 322.98.

[0056] Synthesis of intermediate k

[0057] Dissolve 2-hydroxyl-3-iodo-4,6-dimethoxyacetophenone (32.2g, 0.1mol) and 4-benzyloxybenzaldehyde (21.2g, 0.1mol) in ethanol (350mL) and stir After dissolution, 30% KOH aqueous solution (100 mL) ...

Embodiment 3

[0064] Embodiment 3: the preparation of compound I-4a

[0065]

[0066] Synthesis of intermediate n

[0067] Intermediate m (0.69g, 1.77mmol) was weighed and dissolved in chloroform (70ml). After complete dissolution, tetrabutylammonium tribromide (TBATB, 0.85g, 1.77mmol) was added, stirred at room temperature, and monitored by TLC. After the reaction, the reaction solution was transferred to a separatory funnel. Wash with water and saturated brine successively, dry over anhydrous sodium sulfate, concentrate the organic phase, and perform column chromatography to obtain a yellow solid with a yield of 56%. m.p.230-232℃. 1 H NMR (500MHz, DMSO-d 6 ):δ H =8.07-8.03(m,2H),7.51-7.46(m,4H),7.41(t,J=7.4Hz,4H),7.38-7.33(m,2H),7.22-7.18(m,3H),6.77 (s,1H),6.74(s,1H),5.22(s,2H),4.04(s,3H),3.94(s,3H).MS(ESI):m / z[M+H] + 467.05.

[0068] Synthesis of Intermediate I-3a

[0069] Take compound n (5mmol), 4-carboxyphenylboronic acid (0.9g, 6mmol), anhydrous cesium carbonate (3.9g, 10m...

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Abstract

The invention discloses a flavone derivative and the application thereof. The flavone derivative is a compound with multiple target points and multiple functions for preventing Alzheimer's diseases. The compound and a pharmaceutical salt thereof can be applied to preparation of corresponding medicines, and the compound can be also applied to antioxidants, multiple enzyme inhibitors and metal chelating agents.

Description

technical field [0001] The invention relates to a flavone derivative and its application, in particular to a multi-target, multi-action flavone derivative for anti-Alzheimer's disease, its preparation method and application. Background technique [0002] Alzheimer's disease (AD) is a common neurodegenerative disease worldwide, and its main histopathological features are neurofibrillary tangles, hyperphosphorylation of Tau protein, senile plaques, and β-amyloid deposits. The pathogenesis of AD is complex and difficult to determine. According to its clinical and pathological characteristics, scientists have proposed a variety of hypotheses, such as the cholinergic hypothesis, the amyloid cascade hypothesis, the hyperphosphorylation hypothesis of Tau protein, the inflammation hypothesis, the free radical damage hypothesis, Calcium ion imbalance hypothesis, gene mutation hypothesis, etc. In addition to the NMDA receptor antagonist memantine, the current clinical AD drugs are ma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D311/30A61P25/28
CPCC07D311/30
Inventor 谭桂山刘瑞环徐康平
Owner CENT SOUTH UNIV
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