Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method and pharmaceutical applications of glycosyl modified butylphthalide ring-opened derivatives

A technology of glycosyl modification and butylphthalide, which is applied in the preparation of sugar derivatives, sugar derivatives, sugar derivatives, etc., can solve the problems of complex synthesis and poor stability of sugar-based compounds, and achieve the effect of low drug prices.

Active Publication Date: 2018-05-29
JIANGNAN UNIV
View PDF2 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

On the one hand, the introduction of sugar groups can endow molecules with important properties and spatial electronic properties, increase their structural diversity, thereby enhancing water solubility and bioavailability; on the other hand, it can improve the targeting of drug molecules and enhance drug efficacy. , reduce side effects, improve the kinetic parameters of its metabolism, and regulate the pharmacological activity of molecules. However, there are some problems in sugar modification, such as complex synthesis of glycosyl compounds and poor stability.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method and pharmaceutical applications of glycosyl modified butylphthalide ring-opened derivatives
  • Preparation method and pharmaceutical applications of glycosyl modified butylphthalide ring-opened derivatives
  • Preparation method and pharmaceutical applications of glycosyl modified butylphthalide ring-opened derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Compound I 1 preparation of

[0044] Compound 7 (2.0 mmol) was dissolved in 20 mL of anhydrous acetonitrile, silver nitrate (3.0 mmol) was added, and reacted at 60-70° C. for 2-6 h in the dark. After completion of the reaction, cool to room temperature, filter, concentrate under reduced pressure, dissolve the concentrate in ethyl acetate, stir at room temperature for 10 min, filter, concentrate under reduced pressure, flash column chromatography (PE / EtOAc=5 / 1–1 / 1, v / v) 851 mg of light yellow oil was obtained, the yield was 90%. ee=99.1%.MS(ESI):m / z 474.4[M+H] + . 1 H NMR (300Hz, CDCl 3 ):δ0.89(t,3H,J=6.8Hz),1.24–1.36(m,4H),1.52–1.64(m,2H),3.38–3.42(m,1H),3.45–3.50(m,1H ),3.62–3.68(m,2H),3.70–3.78(m,1H),4.00–4.06(m,1H),4.49(s,2H),6.18(s,1H),6.25–6.32(m,1H ),7.30–7.35(m,2H),7.42(m,1H),7.90(d,1H,J=7.8Hz). 13 C NMR (75MHz, CDCl 3 ):δ171.2,167.9,140.8,132.6,130.6,129.7,128.2,125.8,99.1,75.4,73.1,72.2,70.1,68.8,68.2,59.5,36.6,26.4,23.3,14.0.HRMS(ESI):m / z c...

Embodiment 2

[0045] Embodiment 2 pharmacological test

[0046] In vitro anti-platelet aggregation activity research, the experimental steps are as follows:

[0047] Experimental method: 10 male rabbits, weighing 2.0-2.5kg. The animals were fed for one week under the conditions of 25° C. and relative humidity of 60 to 75%, and then used for experiments. Take 2 rabbits, use lidocaine for local anesthesia, surgically separate the common carotid artery, take blood, take 3.8% sodium citrate 1:9 anticoagulation, and centrifuge at 500r / min for 10min to prepare platelet-rich plasma (PRP), and the remaining Part of it was centrifuged at 3000r / min to prepare platelet-poor plasma (PPP), and the platelet aggregation experiment was carried out by turbidimetric method. Add 240 μL of PRP and 30 μL of different concentrations of test drugs into the measurement tube, incubate for 5 min, add 30 μL of adenosine diphosphate (ADP) (final concentration of 10 μmol / L), 30 μL of thrombin (final concentration of ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a preparation method and pharmaceutical applications of glycosyl modified butylphthalide ring-opened derivatives, and belongs to the fields of carbohydrate chemistry, medicinal chemistry and drug therapeutics. The invention provides obtained butylphthalide ring-opened derivatives, as well as pharmaceutical compositions containing the compounds and the pharmaceutical applications thereof, especially applications in drugs for prevention and treatment of cardio-cerebral ischemia disease, antiplatelet aggregation drugs, antithrombotic drugs, anti-cerebral ischemia drugs, anti-dementia drugs and anti-arteriosclerosis drugs. The results of pharmacological experiments show that the compounds have good antiplatelet aggregation activity and can be used in preparation of drugs for preventing or treating diseases related to platelet aggregation.

Description

technical field [0001] The invention relates to a preparation method and medical application of a glycosyl-modified butylphthalide ring-opening derivative, and belongs to the fields of glycochemistry, medicinal chemistry and drug therapeutics. Background technique [0002] Platelets play an important role in the pathogenesis of arterial thrombotic diseases. Blocking platelet deposition on atherosclerotic plaques and subsequent thrombus formation is the main purpose of antiplatelet drugs. Clinical studies have shown that antiplatelet drugs can effectively reduce the incidence of common cardiovascular and cerebrovascular diseases (such as myocardial infarction, angina pectoris, arrhythmia, coronary heart disease, cerebral ischemia, stroke, cerebral infarction and external vascular diseases). [0003] Butylphthalide, also known as 3-butyl-1(3H)-isobenzofuranone (3-n-Butylphthalide, NBP), is a compound isolated and purified from celery seed. The artificially synthesized NBP rac...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07H13/08C07H1/00A61K31/7024A61P7/02A61P9/10A61P25/28A61P3/10
CPCC07H1/00C07H13/08
Inventor 王晓丽王兆亚郭晓强
Owner JIANGNAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com