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KR-20260067641-A - NOVEL COMPOUNDS AND COMPOSITION FOR INHIBITING HEPATITIS B VIRUS(HBV) PROLIFERATION COMPRISING THE SAME AS AN EFFECTIVE INGREDIENT

KR20260067641AKR 20260067641 AKR20260067641 AKR 20260067641AKR-20260067641-A

Abstract

The present invention relates to a compound represented by the following chemical formula 1: [Chemical Formula 1] (In the above chemical formula 1, R is a substitutable linear or branched C1 - C20 alkyl group, a substitutable C3 - C20 cycloalkyl group, or a substitutable C6 - C20 aryl group, and The above substitution is by oxygen, nitrogen, sulfur, hydroxyl, linear or branched C1 - C6 alkyl groups, C3 - C20 cycloalkyl groups, C6 - C20 aryl groups, halogens, or combinations thereof).

Inventors

  • 김경민
  • 김은하
  • 박주영
  • 사자드 무하마드 아자르
  • 칼숨 파디아
  • 송찬호
  • 하지선
  • 허연정

Assignees

  • 아주대학교산학협력단
  • 대한민국(질병관리청 국립보건연구원장)

Dates

Publication Date
20260513
Application Date
20241106

Claims (14)

  1. Compound represented by the following chemical formula 1: [Chemical Formula 1] (In the above chemical formula 1, R is a substitutable linear or branched C1 - C20 alkyl group, a substitutable C3 - C20 cycloalkyl group, or a substitutable C6 - C20 aryl group, and The above substitution is by oxygen, nitrogen, sulfur, hydroxyl, linear or branched C1 - C6 alkyl groups, C3 - C20 cycloalkyl groups, C6 - C20 aryl groups, halogens, or combinations thereof).
  2. In Article 1, A compound represented by the above chemical formula 1, comprising any one of the following compounds: ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; .
  3. A step of preparing a compound represented by the following chemical formula 4 by reacting a compound represented by the following chemical formula 2 and a compound represented by the following chemical formula 3; A step of preparing a compound represented by the following chemical formula 6 by reacting a compound represented by the above chemical formula 4 with a compound represented by the following chemical formula 5; and A step of preparing a compound represented by Chemical Formula 1 of Claim 1 by substituting a hydroxyl group of a compound represented by Chemical Formula 6 above; including, Method for preparing a compound according to claim 1: [Chemical Formula 2] (In the above Chemical Formula 2, X1 is a halogen or B(OH) 2 ) [Chemical Formula 3] (In the above Chemical Formula 3, X₂ is a halogen or B(OH) ₂ ) [Chemical Formula 4] [Chemical Formula 5] [Chemical Formula 6] .
  4. In Paragraph 3, Of the above X1 and X2 , one is a halogen and the other is B(OH) 2 , Method for manufacturing a compound according to claim 1.
  5. A composition for inhibiting HBV proliferation, comprising a compound according to claim 1 as an active ingredient.
  6. In Article 5, The inhibition of HBc (Hepatitis B core) protein expression in HepG2 cells by a compound represented by the above chemical formula 1, Composition for inhibiting HBV proliferation.
  7. In Article 5, The formation of nucleocapsid in HepG2 cells is inhibited by the above compound, Composition for inhibiting HBV proliferation.
  8. In Article 5, HBV DNA synthesis in HepG2 cells is inhibited by the above compound, Composition for inhibiting HBV proliferation.
  9. In Article 5, HBV DNA synthesis in Huh7 cells is inhibited by the above compound, Composition for inhibiting HBV proliferation.
  10. A pharmaceutical composition for preventing or treating HBV infection, comprising a composition for inhibiting HBV proliferation according to claim 5.
  11. In Article 10, The above pharmaceutical composition for the prevention or treatment of HBV infection further comprises a pharmaceutically acceptable carrier.
  12. In Article 11, A pharmaceutical composition for the prevention or treatment of HBV infection, wherein the carrier comprises a substance selected from the group consisting of lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, menthol, mineral oil, and combinations thereof.
  13. In Article 10, The above pharmaceutical composition for preventing or treating HBV infection further comprises a component selected from the group consisting of preservatives, solubilizers, stabilizers, humectants, sweeteners, coloring agents, flavoring agents, salts, buffers, antioxidants, lubricants, emulsifiers, suspending agents, preservatives, and combinations thereof.
  14. In Article 10, The above pharmaceutical composition for the prevention or treatment of HBV infection is administered by a method selected from the group consisting of intraperitoneal administration, oral administration, inhalation administration, intravenous administration, intramuscular administration, subcutaneous administration, dermal administration, intrauterine administration, tumor administration, rectal administration, and combinations thereof.

Description

Novel Compounds and Composition for Inhibiting Hepatitis B Virus (HBV) Proliferation Comprising the Same as an Effective Ingredient The present invention relates to a novel compound and a composition for inhibiting the proliferation of hepatitis B virus (HBV) containing the same as an active ingredient. Hepatitis B virus (HBV) is one of the major pathogens causing serious health problems worldwide. According to the World Health Organization (WHO), approximately 250 million people are infected with chronic hepatitis B, and about 900,000 people die each year from hepatitis B-related complications. Currently, nucleoside/nucleotide analogs and interferon-alpha are primarily used to treat hepatitis B. However, these treatments have drawbacks, such as difficulty in achieving complete viral elimination, the development of resistance with long-term administration, and side effects. Therefore, there is an urgent need for the development of anti-HBV drugs with novel mechanisms of action. Recent studies have revealed that the sirtuin protein family plays a crucial role in the HBV life cycle. In particular, Sirtuin 2 (SIRT2) is known to act as an important regulator in the process of HBV replication. Consequently, interest in developing inhibitors targeting SIRT2 is growing. AGK2 is one of the well-known SIRT2 inhibitors that demonstrated an inhibitory effect on HBV proliferation in in vitro experiments; however, its clinical application has been limited due to low selectivity and side effects. Therefore, there is a need for research to improve the efficacy of inhibiting HBV proliferation and reduce side effects through the development of new variants based on the structure of AGK2. Korean Patent Publication No. 10-2020-0123392, which is the background technology of the present invention, relates to a composition for inhibiting the proliferation of hepatitis B virus and a method thereof. Figure 1 is the NMR spectrum of a compound according to Example 1 of the present invention. Figure 2 is the NMR spectrum of a compound according to Example 2 of the present invention. Figure 3 is the NMR spectrum of a compound according to Example 3 of the present invention. Figure 4 is the NMR spectrum of a compound according to Example 4 of the present invention. Figure 5 is the NMR spectrum of a compound according to Example 5 of the present invention. Figure 6 is the NMR spectrum of a compound according to Example 6 of the present invention. Figure 7 is the NMR spectrum of a compound according to Example 7 of the present invention. Figure 8 is the NMR spectrum of a compound according to Example 8 of the present invention. Figure 9 is the NMR spectrum of a compound according to Example 9 of the present invention. Figure 10 is the NMR spectrum of a compound according to Example 10 of the present invention. Figure 11 is the NMR spectrum of a compound according to Example 11 of the present invention. Figure 12 is the NMR spectrum of a compound according to Example 12 of the present invention. Figure 13 is the NMR spectrum of a compound according to Example 13 of the present invention. Figure 14 is the NMR spectrum of a compound according to Example 14 of the present invention. Figure 15 is the NMR spectrum of a compound according to Example 15 of the present invention. Figure 16 is the NMR spectrum of a compound according to Example 16 of the present invention. Figure 17 is the NMR spectrum of a compound according to Example 17 of the present invention. Figure 18 is the NMR spectrum of a compound according to Example 18 of the present invention. Figure 19 is the NMR spectrum of a compound according to Example 19 of the present invention. FIG. 20 is the NMR spectrum of a compound according to Example 20 of the present invention. Figure 21 is the NMR spectrum of a compound according to Example 21 of the present invention. Figure 22 is the NMR spectrum of a compound according to Example 22 of the present invention. FIG. 23 is the NMR spectrum of a compound according to Example 23 of the present invention. Figure 24 is the NMR spectrum of a compound according to Example 24 of the present invention. Figures 25a and 25b are the results of a cytotoxicity test according to one experimental example of the present invention. Figure 26 is the result of an experiment on the inhibition of HBV proliferation in liver cancer cell lines by a compound according to Example 1 of the present invention. Embodiments of the present invention are described below with reference to the attached drawings to enable those skilled in the art to easily implement the invention. However, the present invention may be embodied in various different forms and is not limited to the embodiments described herein. Furthermore, in order to clearly explain the present invention in the drawings, parts unrelated to the explanation have been omitted, and similar parts throughout the specification are denoted by similar reference numerals. Throughout this specification, when a part