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

A cyanopyrimidine nucleoside compound and technology of pyrimidine nucleoside, which is applied in the field of pyrimidine nucleoside derivatives, achieves the effects of short synthesis route, significant anti-HIV activity, and simple preparation process

Inactive Publication Date: 2016-06-29
HENAN NORMAL UNIV
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  • 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 type of hybrid inhibitor.

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] 5-(thiazolin-2-yl)-3'-azido-2',3'-dideoxy-5'-acetoxyuridine ( a )Synthesis

[0029] Add 5-cyano-3'-azido-2',3'-dideoxy-5'-acetoxyuridine (0.320g, 1mmol), cysteamine hydrochloride ( 0.170g, 1.5mmol) and chloroform (20mL), stirred, then added sodium acetate (0.123g, 1.5mmol) and DBH (0.014g, 0.05mmol), refluxed and stirred until the reaction was completed (TLC tracking monitoring). The reaction system was cooled to room temperature, and then washed with saturated sodium chloride solution. After the organic phase was dried over anhydrous sodium sulfate, it was spin-dried, and the residue was separated by column chromatography to obtain a light yellow product a (0.247g), yield 65%.

[0030] product a The structural formula and structural characterization data are as follows:

[0031]

[0032] 1 HNMR (400MHz, CDCl 3 )δ:2.13(s,3H),2.53(t, J =6.4Hz,2H),3.22(t, J =8.4Hz,2H),4.06-4.09(m,1H),4.19(t, J =8.4Hz,2H),4.26-4.34(m,3H),6.16(t, J =6.4Hz,1H),8.42(s,1H). 13 CNM...

Embodiment 2

[0034] 5-(thiazolin-2-yl)-3'-azido-2',3'-dideoxyuridine ( b )Synthesis

[0035] In a reaction flask, 5-cyano-3'-azido-2',3'-dideoxyuridine (0.278g, 1mmol), cysteamine hydrochloride (0.170g, 1.5mmol), Sodium acetate (0.123g, 1.5mmol) and DBH (0.014g, 0.05mmol) were mixed uniformly, and the reaction was stirred at 110°C until the reaction was completed (TLC tracking monitoring). The reaction system was cooled to room temperature and washed with saturated sodium chloride solution. After the organic phase was dried over anhydrous sodium sulfate, it was spin-dried, and the residue was separated by column chromatography to obtain a light yellow solid product b (0.237g), yield 70%.

[0036] product b The structural formula and structural characterization data are as follows:

[0037]

[0038] 1 HNMR (400MHz, CDCl 3 )δ:2.44-2.53(m,2H),3.16-3.20(m,2H),3.70-3.72(m,1H),3.91-3.93(m,2H),4.13(t, J =8.4Hz,2H),4.39-4.43(m,1H),6.13(t, J =6.4Hz,1H),8.55(s,1H). 13 CNMR (100MHz, CDCl...

Embodiment 3

[0040] 5-(thiazolin-2-yl)-2'-dehydro-3',5'-diacetoxyuridine ( c )Synthesis

[0041] Add 5-cyano-2'-deoxy-3',5'-bisacetoxyuridine (0.337 g, 1 mmol), cysteamine hydrochloride (0.170 g, 1.5 mmol) and DMF (10mL), stirred, then added sodium bicarbonate (0.126g, 1.5mmol) and DBH (0.014g, 0.05mmol), and stirred the reaction at 100°C until the reaction was completed (TLC tracking monitoring). The reaction system was cooled to room temperature, water (10 mL) was added, and then extracted with ethyl acetate (20 mL×3). The ethyl acetate phases were combined and washed with saturated sodium chloride solution. After the organic phase was dried over anhydrous sodium sulfate, it was spin-dried, and the residue was separated by column chromatography to obtain a white solid product c (0.242g), yield 61%.

[0042] product c The structural formula and structural characterization data are as follows:

[0043]

[0044] 1 HNMR (400MHz, DMSO- d 6 )δ:2.05(s,3H),2.08(s,3H),2.37-2.40(m,2H),...

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Abstract

The invention discloses a 5-substituted pyrimidine nucleoside-thiazoline hybrid with anti-HIV activity and a preparation method thereof. The gist of the technical solution of the present invention is: a 5-substituted pyrimidine nucleoside-thiazoline hybrid with anti-HIV activity, which has the following structure: . The invention also discloses a preparation method of the 5-substituted pyrimidine nucleoside-thiazoline hybrid and a pharmaceutical composition with anti-HIV activity. The 5-substituted pyrimidine nucleoside-thiazoline hybrid provided by the present invention has significant anti-HIV activity, and contains the 5-substituted pyrimidine nucleoside-thiazoline hybrid or its combination with a pharmaceutically acceptable acid or base The pharmaceutical composition of the addition salt can be used for the treatment of AIDS.

Description

technical field [0001] The invention relates to a class of pyrimidine nucleoside derivatives with anti-human immunodeficiency virus (HIV) activity, in particular to a 5-substituted pyrimidine nucleoside-thiazoline hybrid with anti-HIV activity and a preparation method thereof. Background technique [0002] As we all know, AIDS is an infectious disease caused by human immunodeficiency virus (HIV) infection, and HIV reverse transcriptase (RT) plays a very important role in the HIV replication process. Therefore, designing new anti-HIV drugs targeting HIV reverse transcriptase has become one of the commonly used and very effective methods for drug development. The currently developed HIV reverse transcriptase inhibitor drugs can be divided into nucleoside inhibitors (NRTIs) and non-nucleoside inhibitors (NNRTIs) structurally. These HIV reverse transcriptase inhibitors usually have significant curative effect, but also often bring certain toxic and side effects and long-term us...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/24C07H1/00A61K31/7072A61P31/18
Inventor 范学森李坤张新迎郭胜海
Owner HENAN NORMAL UNIV
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