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Cyclocompound of tetrahydropyrrole and dihydroimidazolone as well as preparation and pharmaceutical application thereof

A compound and pharmaceutical technology, which is applied in the field of tetrahydropyrrole and dihydroimidazolone, can solve the problems of no vaccine, high mortality, and no drug for dengue virus

Active Publication Date: 2018-03-20
NANJING TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Under the influence of many factors such as the deterioration of the global environment and warming, the dengue fever epidemic has been expanding in recent years, but there is currently no effective vaccine for preventing the occurrence and prevalence of dengue fever, and there is no effective anti-dengue virus drug available for clinical treatment Dengue disease, clinical treatment is now mainly progressive supportive therapy (intensive supportive therapy), in which maintaining fluid balance is the main means
These limited means cannot deal with the situation that DHF and DSS caused by dengue fever virus infection have a higher mortality rate (~5%), so the drug research on dengue fever disease caused by dengue fever virus infection is extremely important and urgent

Method used

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  • Cyclocompound of tetrahydropyrrole and dihydroimidazolone as well as preparation and pharmaceutical application thereof
  • Cyclocompound of tetrahydropyrrole and dihydroimidazolone as well as preparation and pharmaceutical application thereof
  • Cyclocompound of tetrahydropyrrole and dihydroimidazolone as well as preparation and pharmaceutical application thereof

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Experimental program
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Embodiment 1

[0164] The present invention also provides the preparation method of above-mentioned compound, comprises the following steps:

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[0167] Prepare the following specific compounds according to the above method:

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Embodiment 2

[0186] The constructed NS3-NS2B fusion protein expression plasmid PET15b-CF40-Linker-NS3pro185 (CF40 is the 40 amino acids in the core sequence of the hydrophilic region of NS2B between 1394-1440, Linker is the sequence that Gly4-Ser-Gly4 can rotate freely, NS3pro185 It is the 185 amino acid sequence between 1476-1660 of the N-terminal of NS3) provided by Dr. Siew Phengsuozeg Lim, Novartis Institute of Tropical Diseases, Singapore (see Jun Li, Siew Pheng Lim, David Beer, Viral Patel, Daying Wen, Christine Tumanut, David C . Tully, Jennifer A. Williams, Jan Jiricek, John P. Priestle, Jennifer L. Harris, and Subhash G. Vasudevan J. Biol. Chem. 2005, 280(31), 28766-28774.). NS3-NS2B fusion protein expression plasmid PET15b-CF40-Gly-NS3pro185 in Escherichia coli BL21 (DE3) The recombinantly expressed protease can be used through the histidine tag (His-tag) and Ni 2+ The affinity chromatography column is supplemented with other chromatographic methods for purification, and the puri...

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Abstract

The invention discloses a cyclocompound of tetrahydropyrrole and dihydroimidazolone as well as preparation and pharmaceutical application thereof. The cyclocompound is a compound shown in a formula (I), an isomer or pharmaceutically acceptable salt thereof. The compound, isomer or pharmaceutically acceptable salt thereof can be applied to preparation of medicines used for preventing or treating related diseases (such as dengue fever, dengue hemorrhagic fever, dengue shock syndrome, Zika, Chikungunya, Japanese encephalitis, yellow fever, hepatitis C and West Nile disease) caused by a dengue fever virus and related viruses. (The formula (I) is described in the specification).

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to the pharmaceutical application of tetrahydropyrrole and dihydroimidazolone compound, stereoisomer or pharmaceutically acceptable salt thereof. Background technique [0002] Dengue fever diseases include dengue fever (dengue fever, DF), dengue hemorrhagic fever (dengue hemorrhagic fever, DHF) and dengue shock syndrome (dengue shock syndrome, DSS) symptoms, which are caused by flaviviridae (flaviviridae) dengue virus , DENV) infection. Dengue fever is mainly transmitted in tropical and subtropical regions by Aedes aegypti, Aedes albopictus and Aedes polynesiensis, and is generally bitten by infectious Aedes mosquitoes Dengue fever symptoms appear 3-14 days later (average 4-7 days). The earliest records of dengue fever epidemics were in Asia, Africa, and North America more than 200 years ago. Now dengue fever diseases have occurred in more than 100 countries around t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04C07D519/00C07F5/02A61K31/4188A61K31/69A61P31/18A61P31/14A61P31/20
CPCC07D487/04C07D519/00C07F5/025Y02A50/30
Inventor 周国春徐斌翁智兵姜滨利
Owner NANJING TECH UNIV
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