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

3 ', 4'-unsaturated ribose C-nucleoside analogue and preparation method thereof

A technology for nucleoside analogs and ribonucleosides, which is applied in the field of novel 3',4'-unsaturated-C-ribonucleoside analogs and their preparations, and in the field of antiviral activity, and can solve the problems of insufficient activity to make medicines, etc. Achieve good development prospects, strong stability, and simple operation.

Pending Publication Date: 2022-04-29
ZHENGZHOU UNIV
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the activity of the compound is not enough to be a drug at present, and there is still room for further research

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
  • 3 ', 4'-unsaturated ribose C-nucleoside analogue and preparation method thereof
  • 3 ', 4'-unsaturated ribose C-nucleoside analogue and preparation method thereof
  • 3 ', 4'-unsaturated ribose C-nucleoside analogue and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Example 1: Preparation of ribose C-nucleoside (general formula 2, R=H, CN)

[0040] Dissolve 4-aza-7,9-dideaza-6-methylthioadenine (1g, 6.05mmol) in dry tetrahydrofuran (25mL), add 2M diisopropylamino at -78°C under nitrogen protection Lithium tetrahydrofuran solution (4.5mL, 9.08mmol), after reacting for 30min, add 2,3,5-tri-O-benzylribonolactone (3.04g, 7.26mmol) in tetrahydrofuran (10mL) solution, continue the reaction at -78°C After 1 h, it was quenched by adding saturated ammonium chloride solution, extracted with ethyl acetate, and the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. Silica gel column chromatography (petroleum ether: ethyl acetate volume ratio = 20:1 ~ 5:1) gave oily liquid I (a mixture of α and β configurations).

[0041] Compound I (1.0 g, 1.71 mmol) was dissolved in dichloromethane, under nitrogen protection, triethylsilane (1.13 mL, 6.85 mmol) and boron trifluoride ether solution (430 μL, 3...

Embodiment 2

[0047] Embodiment 2: preparation compound 1a (general formula 1, R=H)

[0048] Suspend compound 2a (0.5g, 1.75mmol) in acetone (37mL, 500mmol), add perchloric acid (225μL, 3.94mmol) and 2,2-dimethoxypropane (216μL, 1.75mmol), stir at room temperature, After the reaction was detected by TCL, it was quenched by adding ammonia water, and the volatile matter was distilled off under reduced pressure. Separation by silica gel column chromatography (dichloromethane: methanol volume ratio = 10:1), rotary evaporation to obtain oily liquid IVa.

[0049] Ⅳa (1g, 3.07mmol), TEMPO (240mg, 1.54mmol), BAIB (3.96g, 12.3mmol) were successively added to the reaction flask, and then acetonitrile / water (V / V=1 / 1, 40mL) was added, and the Stirring, TCL detects that after the reaction is complete, the volatile matter is distilled off under reduced pressure. Acetone and ether were added for recrystallization and filtration to obtain Va as a white solid.

[0050] Suspend Va (0.5g, 1.47mmol) in anhy...

Embodiment 3

[0053] 1 H NMR (400MHz, DMSO) δ7.87(s, 1H), 7.74(s, 2H), 6.84(d, J=4.4Hz, 1H), 6.58(d, J=4.4Hz, 1H), 5.61(d ,J=3.1Hz,1H),5.30(d,J=5.9Hz,1H),5.15(t,J=5.9Hz,1H),5.03(d,J=4.8Hz,2H),3.99–3.93(m , 2H). Embodiment 3: Preparation of compound 1b (general formula 1, R=CN)

[0054] Using the same method as in Example 2, using 2b as a raw material, tetramethylethylenediamine was added to quench after the reduction, and a white solid 1b was obtained.

[0055] 1 H NMR (400MHz, DMSO) δ7.95(d, J=19.7Hz, 3H), 6.91(d, J=4.5Hz, 1H), 6.79(d, J=4.5Hz, 1H), 6.33(d, J =7.0Hz, 1H), 5.36(t, J=5.9Hz, 1H), 5.22(d, J=6.8Hz, 1H), 5.12(s, 1H), 4.07(d, J=5.7Hz, 2H).

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 novel unsaturated nucleoside analogue, particularly relates to a 3 ', 4'-unsaturated-C-ribonucleoside analogue as well as a preparation method and application thereof, and belongs to the field of nucleoside chemistry and medicinal chemistry. The compound has a structure as shown in a general formula 1, wherein R represents H and CN groups; the compound has antiviral activity, can be used as an antiviral agent or a primer of an antiviral drug, and has a good development prospect.

Description

technical field [0001] The invention belongs to the field of nucleoside chemistry and medicinal chemistry, and specifically relates to a novel 3', 4'-unsaturated-C-ribonucleoside analogue, a preparation method thereof and antiviral activity. Background technique [0002] Nucleoside drugs are an important class of drugs used clinically to treat viral infectious diseases and tumors. Nearly 50% of the currently used antiviral drugs are nucleoside drugs. In antiviral chemical drug therapy, nucleoside drugs are currently the most successful antiviral means, and are widely used in the treatment of viral infections such as HSV, HCMV, VZV, HIV, HBV, HCV and HPV. The COVID-19 outbreak that ravaged the world at the end of 2019 is a lung inflammation caused by the Covid-19 virus. Due to the lack of specific therapeutic drugs, the nucleoside drug Remdesivir was approved by the FDA for the treatment of new coronavirus pneumonia amid controversy. . Another more effective nucleoside drug...

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
IPC IPC(8): C07D487/04A61P31/12
CPCC07D487/04A61P31/12
Inventor 刘丰五黄好朱传涛皮特.赫德维恩
Owner ZHENGZHOU 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