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

12-quinoline substituted-andrographolide derivative and preparation method and application thereof

A technology of andrographolide and its derivatives, which can be applied in drug combinations, blood diseases, extracellular fluid diseases, etc., and can solve problems such as insufficient anti-platelet aggregation activity

Active Publication Date: 2019-09-24
江西省中医药研究院
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Andrographolide, as a classic heat-clearing and anti-inflammatory chemical component, has been reported to reduce the mortality rate of myocardial infarction by more than 13%, but there are not many reports on anti-platelet aggregation activity

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
  • 12-quinoline substituted-andrographolide derivative and preparation method and application thereof
  • 12-quinoline substituted-andrographolide derivative and preparation method and application thereof
  • 12-quinoline substituted-andrographolide derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Preparation of compound (II): in the reaction flask, drop 10g (0.0188mol) of compound (I), add 29.7mL of 10% acidic potassium permanganate solution, the molar ratio is 1:1, then add 40mL of dichloromethane, The reaction was stirred for 1 h at room temperature. Thin-layer chromatography monitoring, after the reaction of the raw materials is complete, concentrate to remove the solvent, then add saturated NaCl aqueous solution, extract three times with dichloromethane, combine dichloromethane, anhydrous NaCl 2 SO 4 After drying and concentrating, 6.644 g of white solid was obtained with a yield of 78.2%.

[0027]

[0028] Compound (II): 1H NMR (400 MHz, DMSO-d6): δ=8.79(s,1H),6.13(s,1H),5.19(m,2H),4.67-4.57(m,1H),4.39– 4.17(m, 2H), 2.77–2.56(m, 7H), 2.48(d, J=2Hz, 1H), 2.47(d, J=12Hz, 1H), 2.34(d, J=10Hz, 1H), 1.83 (dd, J1=1.2Hz, J2=10Hz, 1H), 1.67-1.55(m, 2H), 1.55-1.42(m, 2H), 1.32(dd, J1=2Hz, J2=12Hz, 1H), 1.22- 1.08(m,2H),1.01(s,3H),0.87(s,3H);13C NMR(100 MHz,DM...

Embodiment 2

[0030] The preparation of compound (II): in the reaction flask, drop into 10g (0.0188mol) compound (I), add 59.4mL of 10% acidic potassium permanganate solution, the molar ratio is 1.0:2.0, add 40mL methanol again, at 50 ° C, the reaction was stirred for 24h. Thin-layer chromatography monitoring, after the reaction of the raw materials is complete, cool to room temperature, concentrate to remove the solvent, then add saturated NaCl aqueous solution, extract three times with dichloromethane, combine dichloromethane, anhydrous NaCl 2 SO 4 After drying and concentrating, 6.440 g of white solid was obtained with a yield of 75.8%.

Embodiment 3

[0032] Preparation of compound (II): In the reaction flask, drop 10g (0.0188mol) of compound (I), add 38.6mL of 10% acidic potassium permanganate solution, the molar ratio is 1.0:1.3, and then add 40mL of dimethyl methylene Sulfone, stirred and reacted for 10 h at 80°C. Thin-layer chromatography monitoring, after the reaction of raw materials is complete, cool to room temperature, add 20mL of water, extract three times with dichloromethane, combine dichloromethane, then add saturated NaCl aqueous solution, separate liquid, take dichloromethane layer, anhydrous NaCl 2 SO 4 After drying and concentrating, 6.126 g of white solid was obtained with a yield of 72.1%.

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 discloses a 12-quinoline substituted-andrographolide derivative and a preparation method and application thereof. The method comprises the following steps that (1) a compound (I) is taken as a starting material, and a compound (II) is prepared under oxidation of acidic potassium permanganate; (2) a target derivate (IV) is prepared under an alkaline condition by the compound (II) and a 2-methylquinoline compound (III). The preparation method has the advantages that the natural product andrographolide is subjected to structural modification, so that a novel platelet aggregation inhibitor is obtained; the synthetic route is simple and short, the operation is simple and easy to operate, the product structure is novel, and the anti-platelet aggregation effect is equivalent to clopidogrel, which is worthy of further study.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to 12-quinoline substituted-andrographolide derivatives and their preparation methods and applications. Background technique [0002] The natural product andrographolide is a diterpene lactone compound with multiple chiral centers. It has a wide range of biological activities. In addition to the classic anti-inflammatory effects, it also has activities such as enhancing immunity, anti-arteriosclerosis, anti-virus, and anti-tumor. In the past five years, domestic and foreign research on andrographolide has become more in-depth and comprehensive. According to reports, andrographolide can inhibit the differentiation and proliferation of preadipocytes, which is expected to bring good news to overweight patients; it has anti-myocardial weakness activity, which can slow down the apoptosis of cardiomyocytes in patients; it can prevent human obesity by inhibiting the NF-κB pathw...

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): C07D215/14C07D215/18C07D215/20A61P7/02
CPCC07D215/14C07D215/18C07D215/20A61P7/02
Inventor 李雪黄斌彭智祥赵诗云
Owner 江西省中医药研究院
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