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

5-substituted pyrimidine nucleoside-thiazolinone hybrid with anti-HIV activity and preparation method thereof

A formyl pyrimidine nucleoside compound, pyrimidine nucleoside technology, applied in the directions of organic active ingredients, chemical instruments and methods, medical preparations containing active ingredients, etc., can solve problems such as unreported, achieve simple preparation process, synthetic The effect of short route and significant anti-HIV activity

Inactive Publication Date: 2016-06-08
HENAN NORMAL UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there is no report on the structure, synthesis method and anti-HIV activity of this kind of inhibitor hybrid

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
  • 5-substituted pyrimidine nucleoside-thiazolinone hybrid with anti-HIV activity and preparation method thereof
  • 5-substituted pyrimidine nucleoside-thiazolinone hybrid with anti-HIV activity and preparation method thereof
  • 5-substituted pyrimidine nucleoside-thiazolinone hybrid with anti-HIV activity and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1.5-(4-oxo-3-(4-methylpyridin-2-yl)-thiazoline-2-yl)-3'-azido-2', 3'-dideoxy-5' -Synthesis of acetoxyuridine (a)

[0028] Add 5-formyl-3'-azido-2', 3'-dideoxy-5'-acetoxyuridine (0.323g, 1mmol), 4-picoline-2 -Amine (0.108g, 1mmol) and thioglycolic acid (0.184g, 2mmol) and [bmim]PF6 (2mL), the reaction was stirred at 80°C until the end of the reaction (TLC follow the reaction). After the reaction, the reaction system was cooled to room temperature. Extracted three times with ethyl acetate (5 mL×3), combined the ethyl acetate phases, and then washed successively with 5% HCl, 5% NaHCO3 solution, and saturated NaCl solution. The organic phase was collected, dried by adding anhydrous Na2SO4, and then separated by column chromatography to obtain the target product a (0.297g), with a yield of 61%.

[0029] The structural formula of target product a:

[0030]

[0031] 1 HNMR (400MHz, CDCl 3 )δ: 2.15-2.46 (m, 8H), 3.65-3.70 (m, 1H), 4.02-4.35 (m, 5H), 5.98-6.02 (...

Embodiment 2

[0032] Example 2.5-(4-oxo-3-(3-bromophenyl)thiazoline-2-yl)-3'-azido-2',3'-dideoxyuridine (b) synthesis

[0033] Add 5-formyl-3'-azido-2',3'-dideoxyuridine (0.281g, 1mmol), 3-bromoaniline (0.172g, 1mmol) and thioglycolic acid ( 0.184g, 2mmol) and toluene (20mL), reflux reaction until the end of the reaction (TLC tracking reaction). After the reaction was completed, the solvent was evaporated, and the residue was dissolved in ethyl acetate, followed by 5% HCl, 5% NaHCO 3 solution and saturated NaCl solution. Collect the organic phase and add anhydrous Na 2 SO 4 Drying, followed by column chromatography to obtain target product b (0.295g), yield 58%.

[0034] The structural formula of target product b:

[0035]

[0036] 1 HNMR (400MHz, CDCl 3 )δ: 2.28-2.43(m, 2H), 3.54-4.28(m, 7H), 6.04-6.22(m, 2H), 7.20-7.62(m, 4H), 8.23-8.25(m, 1H), 10.04( brs, 1H). 13 CNMR (100MHz, CDCl 3)δ: 30.9, 33.9, 37.7, 38.3, 41.4, 59.6, 60.5, 60.7, 62.7, 63.4, 82.2, 82.7, 86.6, 86.9, 102....

Embodiment 3

[0037] Example 3.5-(4-oxo-3-phenylthiazolin-2-yl)-2',3'-dideoxy-2',3'-didehydro-5'-acetoxyuracil nucleus Synthesis of Glycoside (c)

[0038] In a reaction flask, 5-formyl-2′,3′-dideoxy-2′,3′-didehydro-5′-acetoxyuridine (1.12 g, 4 mmol) was dissolved in tetrahydrofuran (15 mL ), then add aniline (0.186g, 2mmol) and mercaptoacetic acid (0.552g, 6mmol) under ice-water bath conditions, and stir until the reaction is complete (TLC tracking monitoring). The solvent was evaporated, and the residue was dissolved in ethyl acetate, followed by 5% HCl, 5% NaHCO 3 solution, saturated NaCl solution to wash, collect the organic phase, add anhydrous NaCl 2 SO 4 Drying, followed by column chromatography to obtain target product c (0.29g), yield 67%.

[0039] The structural formula of target product c:

[0040]

[0041] 1 HNMR (400MHz, CDCl 3 )δ: 2.05-2.07(m, 3H), 3.72-4.22(m, 4H), 5.78-5.82(m, 1H), 5.94(s, 1H), 6.20-6.25(m, 1H), 6.78-6.82( m, 1H), 7.22-7.38 (m, 7H), 9.42 (brs, 1H)....

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 5-substituted pyrimidine nucleoside-thiazolidinone hybrid with anti-HIV activity and a preparation method thereof. In a structural formula of a compound A, R1 represents one of (2R, 4S, 5S)-4-azido-2, 3, 4, 5-tetrahydro-5-(acetyloxy)methyl furan-2- group, (2R, 4S, 5S)-4-azido-2, 3, 4, 5-tetrahydro-5-hydroxymethyl furan-2- group, (2R, 5S)-2, 5-dihydro-5- (acetyloxy)methyl furan-2- group, (2R, 5S)- 2, 5-dihydro-5- hydroxymethyl furan-2- group; and R2 represents one of phenyl, substituted phenyl, pyridyl, substituted pyridyl, alkyl, naphthenic, propargyl, benzyl, etc. The 5-substituted pyrimidine nucleoside-thiazolidinone hybrid with anti-HIV activity, contains at least one compound A, or an additive salt formed by a pharmaceutically-acceptable acid or alkali, individually or combining one or more pharmaceutically-acceptable, inert and nontoxic excipients or carriers, forms a pharmaceutical composition, and the pharmaceutical composition is used for preparing an anti-AIDS medicament.

Description

Technical field: [0001] The invention relates to a class of compounds with the activity of inhibiting human immunodeficiency virus (HIV), in particular to a 5-substituted pyrimidine nucleoside-thiazolinone hybrid with anti-HIV activity and a preparation method thereof. Background technique: [0002] AIDS is an epidemic infectious disease caused by human immunodeficiency virus (HIV) infection, and HIV reverse transcriptase (RT) plays a very important role in the process of HIV replication. Selective HIV reverse transcriptase inhibitors, as anti-HIV drugs, are one of the hot spots in drug research and development. Among the more than 30 anti-HIV drugs on the market, 17 are HIV reverse transcriptase inhibitors. HIV reverse transcriptase inhibitors can be further divided into nucleoside inhibitors (NRTIs) and non-nucleoside inhibitors (NNRTIs). All of them can effectively inhibit the replication of HIV, thereby greatly reducing the morbidity and mortality of virus infection. ...

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 Patents(China)
IPC IPC(8): C07H19/06C07H1/00C07D417/14A61K31/7072A61K31/513A61P31/18
Inventor 范学森张新迎李晓严王洋洋徐海云郭胜海何艳
Owner HENAN NORMAL 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