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Carbamate derivates of scutellarin and seutellarein, and application thereof

A technology of aglycon carbamate and scutellarin aglycon, which is applied in the field of pharmacy, and can solve the problems of high oral bioavailability, low oral bioavailability, and unsatisfactory drug efficacy.

Inactive Publication Date: 2014-04-23
GUIYANG MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The purpose of the present invention is to provide a kind of scutellarin and its aglycon carbamate derivatives and its application, the compound has high oral bioavailability, and has the selectivity of anti-neurodegenerative diseases, so as to solve the problem of scutellarin Low oral bioavailability and unsatisfactory drug efficacy in clinical application

Method used

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  • Carbamate derivates of scutellarin and seutellarein, and application thereof
  • Carbamate derivates of scutellarin and seutellarein, and application thereof
  • Carbamate derivates of scutellarin and seutellarein, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0109] Add methyl ethyl acetate (770mg, 1.6mmol) to a 100ml dry reaction bottle, 15ml of anhydrous DMF to make it completely dissolved, dissolve tert-butyl-protected glycine isocyanate (381mg2.43mmol) with 10ml of anhydrous THF and add to the reaction system , added triethylamine (34.02μL, 0.243mmol), reacted at 50°C under nitrogen protection for 10 hours, evaporated the solvent under reduced pressure, separated and purified by silica gel column chromatography, and the eluent was chloroform:methanol=15:1 (volume ratio) to obtain 374.6 mg of white-like scutellarin-6″-methyl ester 4′-tert-butyl-protected glycine carbamate solid, with a yield of 37%;

[0110] 1 H-NMR (400MHz, DMSO-d 6 ): δ13.05(brs, 1H), 10.46(brs, 1H), 8.18(t, 1H, J=5.6Hz), 7.97(d, 2H, J=8.8Hz), 7.12(s, 1H), 6.95 (d, 2H, J=8.8Hz), 6.92(s, 1H), 5.53(d, 1H, J=5.6Hz), 5.34(brs, 2H), 5.20(brs, 1H), 4.21(d, 1H, J=9.6Hz), 3.73(d, 2H, J=6.0Hz), 3.65(s, 1H), 1.42(s, 9H).

[0111] The compound (158 mg, 0.24 mmol) obt...

Embodiment 2

[0114] Add methyl ethyl acetate (650mg, 1.37mmol) to a 100mL dry reaction flask, dissolve it completely in 15mL of anhydrous DMF, dissolve tert-butyl-protected alanine isocyanate (351mg, 2.05mmol) in 10mL of anhydrous THF, and add Add triethylamine (28.7μL, 0.205mmol) to the reaction system, react at 50°C for 10 hours under nitrogen protection, evaporate the solvent under reduced pressure, separate and purify by silica gel column chromatography, and the eluent is chloroform:methanol=15:1 (V / V) to obtain 457.8 mg of white-like scutellarin-6″-methyl ester 4′-tert-butyl-protected alanine carbamate solid, with a yield of 51.6%.

[0115] 1 H-NMR (400MHz, DMSO-d 6 ): δ13.05(brs, 1H), 10.46(brs, 1H), 8.25(d, 1H, J=7.2Hz), 7.97(d, 2H, J=8.8Hz), 7.12(s, 1H), 6.95 (d, 2H, J=8.8Hz), 6.90(s, 1H), 5.54(d, 1H, J=4.8Hz), 5.36(brs, 2H), 508(brs, 1H), 4.21(d, 1H, J=9.2Hz), 3.99(m, 1H), 1.40(s, 9H), 1.31(d, 3H, J=7.2Hz).

[0116] The compound (158mg0.24mmol) obtained in the previous step wa...

Embodiment 3

[0119] Add methyl ethyl acetate (680.68mg1.34mmol) to a 100mL dry reaction bottle, 15mL of anhydrous DMF to make it completely dissolved, dissolve tert-butyl-protected valamino acid isocyanate (428mg, 2.15mmol) with 10mL of anhydrous THF and add Add triethylamine (28.0 μL, 0.200 mmol) to the reaction system, react at 50°C for 10 hours under nitrogen protection, evaporate the solvent under reduced pressure, separate and purify by silica gel column chromatography, and the eluent is chloroform:methanol=15:1 (Volume ratio), 398.1 mg of white-like scutellarin-6″-methyl ester 4′-tert-butyl-protected valine carbamate solid was obtained, with a yield of 44%.

[0120] 1 H NMR (400MHz, DMSO-d 6 ): δ13.07(brs, 1H), 10.48(brs, 1H), 8.14(d, 1H, J=8.4Hz), 7.99(d, 2H, J=8.8Hz), 7.13(s, 1H), 6.97 (d, 2H, J=8.8Hz), 6.92(s, 1H), 5, 53(brs, 1H), 5.38(brs, 2H), 512(brs, 1H), 4.21(d, 1H, J=9.2 Hz), 3.87-3.83(m, 1H), 3.67(s, 3H), 2.12-2.07(m, 1H), 1.44(s, 9H), 0.96(d, 6H, J=9.2Hz).

[0121] The...

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Abstract

The invention discloses flavonoid compounds which can treat neurodegenerative disease and have the structures represented by the following structure general formula I, II and III, and preparation methods and an application thereof. Physicochemical properties and in-vitro metabolism experiments prove that the compounds have better physicochemical and metabolic properties compared with scutellarin and seutellarein, and can be applied in preparation of drugs for treating the neurodegenerative disease.

Description

technical field [0001] The invention relates to the field of pharmacy, in particular to scutellarin and its aglycon carbamate derivatives and applications thereof. Background technique [0002] Neurodegenerative disease is a disease state in which neurons of cells in the brain and spinal cord are lost, which worsens over time and eventually leads to brain dysfunction (Appel S.H. et al. Adv Neurol. 1996, 69, 153- 159) Neurodegenerative diseases mainly include Alzheimer's disease (Alzheimer's Disease, AD), Parkinson's disease (Parkinson's disease, PD) and amyotrophic lateral sclerosis (Amyotrophic Lateral Sclerosis, ALS). Their common feature is the irreversible damage and death of neuron function in a specific area, and there is no ideal method for treating such diseases so far. As my country enters an aging society, the incidence of neurodegenerative diseases has risen sharply, becoming one of the main causes of death. Therefore, the treatment of such diseases is one of th...

Claims

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Application Information

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IPC IPC(8): C07H17/07C07H1/00C07D311/30A61K31/7048A61K31/352A61P25/28A61P25/16
Inventor 傅晓钟王永林姜凤洁兰燕宇李勇军王爱民董永喜黄勇周雯查雨锋张顺刘宗元欧瑜
Owner GUIYANG MEDICAL UNIVERSITY
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