Top > Search of International Patents > ANTI-HEPATOMA-VIRUS AGENT

ANTI-HEPATOMA-VIRUS AGENT

Foreign code F170009243
File No. (S2016-0463-N0)
Posted date Sep 21, 2017
Country WIPO
International application number 2017JP009674
International publication number WO 2017155082
Date of international filing Mar 10, 2017
Date of international publication Sep 14, 2017
Priority data
  • P2016-048664 (Mar 11, 2016) JP
Title ANTI-HEPATOMA-VIRUS AGENT
Abstract The purpose of the present invention is to provide a novel therapeutic agent against hepatoma viruses. Specifically, the present invention pertains to an anti-hepatoma-virus agent containing, as an active ingredient, a compound represented by general formula (I): (in the formula, R1 is fluorine or hydrogen) or a pharmacologically acceptable salt thereof.
Outline of related art and contending technology BACKGROUND ART
With respect to the viral infection, variola vaccine therapy by is discovered, and it becomes possible to prevent infection. However, the vaccine virus is not present, there is a possibility that the virus infection and the individual's immune exclusion, only symptomatic treatment choices. The history of the development anti-viral agents against the virus of the herpes simplex virus et al. 1977 years acyclovir therapeutic agent begins. 1985 Year et al. human immunodeficiency virus 1 (HIV-1) of the therapeutic agent azidothymidine is found. Development of anti-viral agents, HIV-1, hepatitis B virus (HBV), hepatitis C virus (HCV), in some viruses such as influenza virus so that the user is, most of the virus in the current situation has still not been developed.
HCV and HBV is chronic hepatitis, cirrhosis, liver tumor liver cancer caused by virus. About 200 million HCV infected persons within the country, and in the world it is estimated that about 2 million. About 150 million HBV infected persons within the country, and in the world it is estimated that about 3.5 million. HCV and HBV of infected persons of the world population and to about 8%, to be overcome one of the most important infection is 1.
Is a Flaviviridae HCV 1 belonging to the genus to single-stranded positive RNA genome and is a virus. Virus genome is approximately 9600 nucleotides, replication of a virus growth is performed all in the cytoplasm. Entering the first virus infects the cells, about 3000 amino acid residues from the precursor protein is produced. Then, the host proteolytic enzyme with proteolytic enzymes of the virus by 10 types of mature virus protein is produced. 10 Among the types of proteins, E1, E2, Core, p7 virus particles for the production of structural protein. NS2, NS3, NS4A, NS4B, NS5A, NS5B Necessary for replication of the virus non-structural protein. Shown in Fig. 1 to the life cycle of HCV.
The life cycle of HCV, as follows: 1) virus infection in the infection step within a cell and contacted with the receptor to enter. The current, as a receptor of HCV, CD81, SR-B1, Claudin 1 known Occludin and the like.
2) Most of the host protein translation, translation of the mRNA at the 5' terminus Cap structures. On the other hand, in the structure does not require Cap HCV. Of the HCV 5' on the side of the primary structure of a region referred to as Internal Ribosomal Entry Site(IRES) Ribosome 2 directly bonded to each other, Cap-independent translation by the virus (about 3000 amino acids) the precursor protein is translated. Type 10 precursor protein from the host proteolytic enzyme with the viral proteins of the virus itself (NS3-4A) produced by proteolytic enzymes.
3) Replication from the replication of the HCV replication complex consisting of the non-structural protein is carried out by. Initially, plus-strand viral RNA-dependent RNA polymerase as a template (NS5B) by the action of a minus-strand RNA replication intermediates in the synthesis. Next, a minus-strand RNA as a template to NS5B plus-strand RNA by the viral genome is replicated.
4) And virus particle formation Lipid Droplet Endoplasmic Reticulum particles may be formed as a scaffold, structural proteins Core, E1, E2 to collect the viral genome to be completed. In this case, NS5A is known to be an important role.
5) Released viruses released in the form of particles outside the cell, at this time apolipoprotein has been found to be necessary.
The growth of one or more HCV only occurs in the cytoplasm.
A virus that has been the clinical application of the virus that act directly on the degradative enzyme Direct-Acting Antivirals (DAAs) NS3-4A protein, the replication of a virus, and NS5A required to form particles, the RNA-dependent RNA polymerase NS5B targets. Interferon (IFN) in chronic hepatitis C monotherapy has been is carried out first is, at this time the effectiveness of was about 10%. 2015 In the year NS5B in combination with an inhibitor of NS5A inhibition of approved treatments, the effectiveness of 90% or more have been reported.
On the other hand, as shown in Fig. 2 to the life cycle of HBV. Incomplete Hepadnaviridae HBV 2 belonging to the genus is single-stranded DNA virus. Intracellular HBV 2 completely penetrates into the nucleus to form a double-stranded DNA, and cccDNA. Of 3.6,2.4,2.1,0. 7 kb mRNA as a template DNA is transferred onto the, polymerase, (Core) HBcAg, HBsAg, translated into protein X. Of the pregenomic RNA(pgRNA) Core is 3.6kb, which is packaged along with polymerase. After pgRNA is reversely transferred DNA virus particles released outside the cell. Is a retrovirus HBV polymerase in reverse transcriptase activity is not due to, for the treatment HIV-1 reverse transcriptase inhibitors are being used.
Also, for example, Patent Document 1 is, 2 '- fluoro -6' - methylene carbon of the ring nucleosides used in the treatment of HBV and HCV infection by the threshold value. However, Patent Document 1 is, as anti-viral testing of actual test only discloses the anti-HBV, 2 '- fluoro -6' - methylene carbon ring using nucleosides, to treat the infection of both HBV and HCV was able to not.
Scope of claims (In Japanese)[請求項1]
以下の一般式(I):
[化1]
(式中、R1は、フッ素又は水素である)
で示される化合物又はその薬学的に許容される塩を有効成分として含有する、抗肝腫瘍ウイルス剤。
[請求項2]
一般式(I)で示される化合物又はその薬学的に許容される塩が2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩であり、且つ肝腫瘍ウイルスがB型肝炎ウイルス及び/又はC型肝炎ウイルスである、請求項1記載の抗肝腫瘍ウイルス剤。
[請求項3]
一般式(I)で示される化合物又はその薬学的に許容される塩が2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩であり、且つ肝腫瘍ウイルスがB型肝炎ウイルス又はC型肝炎ウイルスである、請求項1記載の抗肝腫瘍ウイルス剤。
[請求項4]
一般式(I)で示される化合物又はその薬学的に許容される塩が2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩であり、且つ肝腫瘍ウイルスがB型肝炎ウイルスである、請求項1記載の抗肝腫瘍ウイルス剤。
[請求項5]
一般式(I)で示される化合物又はその薬学的に許容される塩が2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩であり、且つ肝腫瘍ウイルスがC型肝炎ウイルスである、請求項1記載の抗肝腫瘍ウイルス剤。
[請求項6]
一般式(I)で示される化合物又はその薬学的に許容される塩が2-クロロ-9-(2-デオキシ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩であり、且つ肝腫瘍ウイルスがC型肝炎ウイルスである、請求項1記載の抗肝腫瘍ウイルス剤。
[請求項7]
請求項1記載の抗肝腫瘍ウイルス剤を含有する肝腫瘍ウイルス関連疾患予防又は治療剤であって、前記関連疾患が慢性肝炎、肝硬変及び肝癌から成る群より選択される、前記予防又は治療剤。
[請求項8]
2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩である抗肝腫瘍ウイルス剤を含有し、且つ肝腫瘍ウイルス関連疾患がB型肝炎ウイルス及び/又はC型肝炎ウイルス関連疾患である、請求項7記載の予防又は治療剤。
[請求項9]
2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩である抗肝腫瘍ウイルス剤を含有し、且つ肝腫瘍ウイルス関連疾患がB型肝炎ウイルス又はC型肝炎ウイルス関連疾患である、請求項7記載の予防又は治療剤。
[請求項10]
2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩である抗肝腫瘍ウイルス剤を含有し、且つ肝腫瘍ウイルス関連疾患がB型肝炎ウイルス関連疾患である、請求項7記載の予防又は治療剤。
[請求項11]
2-クロロ-9-(2-デオキシ-2-フルオロ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩である抗肝腫瘍ウイルス剤を含有し、且つ肝腫瘍ウイルス関連疾患がC型肝炎ウイルス関連疾患である、請求項7記載の予防又は治療剤。
[請求項12]
2-クロロ-9-(2-デオキシ-β-D-アラビノフラノシル)アデニン又はその薬学的に許容される塩である抗肝腫瘍ウイルス剤を含有し、且つ肝腫瘍ウイルス関連疾患がC型肝炎ウイルス関連疾患である、請求項7記載の予防又は治療剤。
  • Applicant
  • ※All designated countries except for US in the data before July 2012
  • National university corporation Kagoshima University
  • NATIONAL UNIVERSITY CORPORATION OKAYAMA UNIVERSITY
  • DAIKIN INDUSTRIES LTD
  • Inventor
  • IKEDA Masanori
  • TAKEDA Midori
  • BABA Masanori
  • KATO Nobuyuki
IPC(International Patent Classification)
Specified countries National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
Please contact us by E-mail if you have any interests on this patent.

PAGE TOP

close
close
close
close
close
close