Application of polycyclic polyketides in preparation of anti-herpesvirus drugs

An anti-herpes virus and polyketide compound technology, applied in antiviral agents, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve problems such as easy mutation, high drug resistance, and low protein quantity

Active Publication Date: 2019-08-02
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the simple structure of the virus itself and the small number of proteins, it is easy to mutate under the repeated action of antiviral drugs and has high drug resistance. Therefore, the application effect of antiviral drugs currently used in clinical practice is not ideal.

Method used

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  • Application of polycyclic polyketides in preparation of anti-herpesvirus drugs
  • Application of polycyclic polyketides in preparation of anti-herpesvirus drugs
  • Application of polycyclic polyketides in preparation of anti-herpesvirus drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] 6,8-dihydroxy-9-isobutyl-2,2,4,4-tetramethyl-4,9-dihydro-1H-xanthene-1,3(2H)-dione intermediate ( 52) Preparation

[0093]

[0094] first step

[0095] At room temperature, dissolve phloroglucinol 52a (2.5g, 20mmol) in nitromethane solution, add anhydrous aluminum chloride (10.7g, 80mmol) and isobutyryl chloride (2.3g, 22mmol) successively, and heat up to reflow. After reacting for 12 hours, the reaction solution was slowly poured into ice water, and saturated sodium potassium tartrate solution (100 mL) was added, followed by vigorous stirring. The reaction solution was extracted 3 times with ethyl acetate (100 mL×3). The organic phases were combined and washed with saturated NaCl solution. After drying and filtering over anhydrous sodium sulfate, the organic phase was evaporated to dryness under reduced pressure. The resulting crude product was separated and purified by silica gel column chromatography to obtain compound 52c (3.6 g, yield 85%).

[0096] second...

Embodiment 2

[0104] 6,8-Dihydroxy-9-cyclobutyl-2,2,4,4-tetramethyl-4,9-dihydro-1H-xanthene-1,3(2H)-dione intermediate ( 53) Preparation

[0105]

[0106] first step

[0107] At room temperature, dissolve phloroglucinol 52a (2.5g, 20mmol) in nitromethane solution, add anhydrous aluminum chloride (10.7g, 80mmol) and cyclobutyryl chloride (2.6g, 22mmol) successively, and heat up to reflow. After reacting for 12 hours, the reaction solution was slowly poured into ice water, and saturated sodium potassium tartrate solution (100 mL) was added, followed by vigorous stirring. The reaction solution was extracted 3 times with ethyl acetate (100 mL×3). The organic phases were combined and washed with saturated NaCl solution. After drying and filtering over anhydrous sodium sulfate, the organic phase was evaporated to dryness under reduced pressure. The obtained crude product was separated and purified by silica gel column chromatography to obtain compound 53c (3.4 g, yield 83%).

[0108] sec...

Embodiment 3

[0116] 6,8-Dihydroxy-5-acetyl-9-isobutyl-2,2,4,4-tetramethyl-4,9-dihydro-1H-oxanthene-1,3(2H)- Preparation of diketone (5)

[0117] At room temperature, compound 52 (44.2 mg, 0.1 mmol) was dissolved in glacial acetic acid solution (4 mL), acetic anhydride (20.6 μL, 0.22 mmol) and boron trifluoride diethyl ether (13.6 μL, 0.105 mmol) were added, and the temperature was raised to 100°C. After reacting for 3 hours, the reaction was cooled down to room temperature, 1N aqueous sodium hydroxide solution (4 mL) was added to quench the reaction, and extracted three times with ethyl acetate (8 mL×3). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain a crude product. The obtained crude product was recrystallized in a mixture of dichloromethane and n-hexane to obtain compound 5 (16.0 mg, yield 40%).

[0118] 1 H NMR (500MHz, CDCl 3 )δ13.54(s,1H),7.09(s,1H),6.28(s,1H),4.33(t,J=6.1Hz,1H),2.82(s,3H),1.65(s,3H), 1.50(...

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PUM

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Abstract

The invention discloses application of polycyclic polyketides in the preparation of anti-herpesvirus drugs. According to the invention, the polyketides are found to inhibit diseases caused by herpes simplex virus (HSV) type I, HSV-2, varicella zoster virus (VZV) and cytomegalo virus (CMV) infection. Compared with drugs such as acyclovir on the market, the compound in the invention exhibits considerable activity, but the mechanism of action is different, and the compound overcomes the drug resistance of the drugs currently on the market. Thus, these compounds have good application prospects inthe treatment of diseases caused by HSV-1, HSV-2, VZV and CMV infection.

Description

technical field [0001] The present invention relates to a class of medicine for treating and preventing herpes virus infection. More specifically, the present invention relates to a class of polycyclic polyketide compounds used in the preparation of anti-herpes simplex virus type I (Herpes simplex virus-1, HSV-1), herpes simplex virus type II (Herpes simplex virus-1, HSV -2), varicella-zoster virus (Varicellazoster virus, VZV) and cytomegalovirus (Cytomegalo virus, CMV) in the application of four herpes virus drugs. Background technique [0002] Herpes viruses (Herpes viruses, HV) are a class of enveloped viruses with double-stranded DNA genomes. Viruses of this family can spread widely in animals and humans, infect long-term stealth, and induce corresponding diseases. According to the differences in genome sequence, structure and physical and chemical properties, the herpesviruses found to infect humans can be divided into three subfamilies: α-herpesvirinae, β-herpesvirin...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P31/22
CPCA61K31/352A61P31/22
Inventor 叶文才李药兰王英李满妹胡利军唐维程民井苏骏成
Owner JINAN UNIVERSITY
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