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Use of dipeptide analogue

A technology of uses and drugs, applied in the field of medicinal chemistry, can solve problems such as no vaccine, no drug for dengue virus, high mortality rate, etc.

Active Publication Date: 2015-05-27
NANJING TECH UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] 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 For dengue fever, the current clinical treatment is mainly intensive supportive therapy, in which maintaining fluid balance is the main means
These limited means cannot cope with the high mortality rate (~5%) of DHF and DSS caused by dengue virus infection, so the drug research on dengue fever disease caused by dengue virus infection is extremely important and urgent

Method used

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Embodiment 1

[0027]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 purifi...

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Abstract

The present invention discloses the use of dipeptide analogs, especially the use of compounds of formulas (I) and (II), stereoisomers or pharmaceutically acceptable salts thereof in pharmaceuticals. The compounds represented by formula (I) and formula (II) may be used as drugs for the treatment and prevention of diseases caused by dengue virus. At the same time, they may also be used as drugs for the treatment and prevention of diseases caused by other flaviviruses, such as yellow fever and hepatitis C. , Japanese encephalitis, forest encephalitis, diseases caused by West Nile virus infection or AIDS caused by HIV, etc.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and specifically relates to the application of dipeptide analog compounds, stereoisomers, or pharmaceutically acceptable salts thereof in pharmacy. Background technique [0002] The compound of formula (I) has been used as the substrate of methionine aminopeptidase for drug screening of angiogenesis (Ying Zhou, Xiao-Chuan Guo, Tian Yi, Tadashi Yoshimoto, Dehua Pei Analytical Biochemistry 2000, 280, 159-165. ) [0003] [0004] And formula (II) is the raw material of formula (I) (Ying Zhou, Xiao-Chuan Guo, Tian Yi, Tadashi Yoshimoto, Dehua Pei Analytical Biochemistry 2000, 280, 159–165.) [0005] [0006] Dengue fever disease includes dengue fever (dengue fever, DF), dengue hemorrhagic fever (dengue hemorrhagic fever, DHF) and dengue shock syndrome (dengue shock syndrome, DSS) symptoms, it is caused by the flaviviridae dengue virus (dengue virus, DENV) infection. Dengue fever is mainly ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/05A61P31/14A61P31/18
CPCY02A50/30
Inventor 周国春翁智兵王春光邵晓霞聂鑫
Owner NANJING TECH UNIV
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