WO2004080453A1 - 抗c型肝炎ウイルス剤と抗hiv剤 - Google Patents
抗c型肝炎ウイルス剤と抗hiv剤 Download PDFInfo
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- WO2004080453A1 WO2004080453A1 PCT/JP2004/003080 JP2004003080W WO2004080453A1 WO 2004080453 A1 WO2004080453 A1 WO 2004080453A1 JP 2004003080 W JP2004003080 W JP 2004003080W WO 2004080453 A1 WO2004080453 A1 WO 2004080453A1
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- fullerene
- hepatitis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/70—Nanostructure
- Y10S977/734—Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/70—Nanostructure
- Y10S977/734—Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
- Y10S977/735—Carbon buckyball
- Y10S977/737—Carbon buckyball having a modified surface
- Y10S977/738—Modified with biological, organic, or hydrocarbon material
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/70—Nanostructure
- Y10S977/734—Fullerenes, i.e. graphene-based structures, such as nanohorns, nanococoons, nanoscrolls or fullerene-like structures, e.g. WS2 or MoS2 chalcogenide nanotubes, planar C3N4, etc.
- Y10S977/735—Carbon buckyball
- Y10S977/737—Carbon buckyball having a modified surface
- Y10S977/74—Modified with atoms or molecules bonded to the surface
Definitions
- the invention of this application relates to an anti-hepatitis C virus agent or an anti-HIV agent. More specifically, the invention of this application relates to a new anti-hepatitis C virus agent or anti-HIV agent containing a fullerene derivative or a quaternary amine salt as an active ingredient.
- Non-patent Document 1 discloses compounds of the following formula having HIV inhibitory activity.
- RNA polymerase inhibition and HIV reverse transcriptase inhibition of hepatitis C virus.
- Hepatitis C virus is transmitted through blood, etc. and causes chronic hepatitis. Patients with 0 infection tend to develop cirrhosis and liver cancer, and the natural cure rate is extremely low.
- the current treatment is interferon administration, which may be combined with ripavirin. However, the HCV exclusion rate is as low as one third. Therefore, the development of new anti-HCV drugs is desired.
- HCV is an RNA virus that, after entering human hepatocytes, makes several silicons based on its own RNA using the protein synthesis system of the host (human) cells.
- One of those enzymes is HCV RNA polymerase, which is essential for HCV growth.
- HIV human immunodeficiency virus
- HIV is similar to the hepatitis C virus and is an RNA virus.
- Hi One is a reverse transcriptase inhibitor that synthesizes DNA based on HIV RNA, and the other is an enzyme required for the growth of HIV (synthesized by HIV protease and viral RNA).
- Nucleobase analogs are mainly used as reverse transcriptase inhibitors, but they have drawbacks such as being toxic to human cells.
- proteaase inhibitors that are stable in vivo and have high activity. In this way, there are currently no specific medicines for AIDS, but it is also a big problem that HIV acquires resistance to these drugs.
- fullerene derivatives have been reported to inhibit HIV protease activity.
- various other derivatives have been tried, but no fullerene derivative having an HIV reverse transcriptase inhibitory activity has been reported.
- Non-Patent Document 1 R. F. Schinazi, et al., Antimicrob. Agents
- the invention of this application is a novel hepatitis C virus RNA polymerase inhibitory activity or HIV reverse transcriptase inhibitory activity having a fullerene derivative as an active ingredient. It is an object to provide an anti-HIV agent having the above.
- This application provides the following inventions for solving the above-mentioned problems.
- It contains a fullerene derivative having a nitrogen atom constituting a ring together with a pair of adjacent bonded carbon atoms constituting one skeleton of a fullerene carbon cluster, or a quaternary amine salt thereof as an active ingredient.
- ⁇ and ⁇ indicate adjacent carbon atoms constituting the fullerene carbon cluster skeleton, and 1 ⁇ ⁇ 11 2 may be the same or different and may have a substituent.
- a hydrogen group, and R 3 and R 4 are the same or different and each represents a hydrogen atom or an optionally substituted hydrocarbon group
- ⁇ which provides an anti-hepatitis C virus agent or an anti-neoplasm IV agent, comprising as an active ingredient a fullerene derivative quaternary amine salt having an organic bond structure represented by
- ⁇ and ⁇ represent adjacent carbon atoms constituting one skeleton of a fullerene carbon cluster, and R 3 and R 4 are the same or different and each has a hydrogen atom or a substituent.
- An anti-hepatitis C virus agent or anti-HIV agent comprising a fullerene derivative having an organic bond structure represented by the formula: [5] At least one of the adjacent bonded carbon atom pairs that constitute one skeleton of a fullerene carbon cluster has the following formula:
- a and B represent adjacent carbon atoms constituting the fullerene carbon cluster skeleton, and R 6 and R 7 are the same or different and each has a hydrogen atom or a substituent. And D and E are the same or different and each represents a hydrocarbon group which may have a substituent)
- An anti-hepatitis C virus agent or anti-HIV agent characterized by containing a fullerene derivative having an organic bond structure represented by the formula (II) or a quaternary amine salt thereof as an active ingredient.
- An anti-hepatitis C virus agent or anti-HIV agent characterized in that the hydrocarbon group is a linear, branched or cyclic hydrocarbon group.
- At least one of the adjacent bonded carbon atom pairs that constitute one skeleton of a fullerene carbon cluster has the following formula:
- a and B represent adjacent carbon atoms constituting the fullerene carbon cluster skeleton
- R 8 and R 9 are the same or different and each represents a hydrogen atom or a COOR group
- R represents a hydrogen atom or a hydrocarbon group that may have a substituent
- R 1 Q represents a carbon hydrogen chain that may have a substituent
- the hydrocarbon chain has a heteroatom through a different atom.
- R 1 1 R 1 2 and R 13 are the same or different and each represents a hydrogen atom or a hydrocarbon group which may have a substituent.
- the active ingredient of the anti-hepatitis C virus agent or anti-HIV agent of the invention of this application is a fullerene derivative having a structure represented by the above formula or a quaternary amine salt or fullerene carboxyl derivative thereof.
- the sign in the above formula ! ⁇ 2 and R 5 are the same or different and each represents an optionally substituted hydrocarbon group, and R 3 and R 4 , and R 6 and R 7 are the same or different.
- a hydrogen atom or a hydrocarbon group which may have a substituent is shown, but here, as the hydrocarbon group, various chain or cyclic groups, and various saturated or unsaturated groups are considered. Is done. A variety of aliphatic, cycloaliphatic and aromatic hydrocarbons are considered.
- examples of the hydrocarbon group include a linear or branched aliphatic hydrocarbon group.
- the number of carbon atoms is not limited, but, for example, those having about 1 to 16 carbon atoms are preferred.
- the symbols D and E in the above formulas are the same or different and each represents a hydrocarbon chain that may have a substituent.
- the hydrocarbon chain is an alkyl having 1 to 3 carbon atoms. Chains are exemplified as suitable, for example.
- the substituent which may be bonded to the above hydrocarbon group or hydrocarbon chain may be appropriate.
- an alkoxy group, an acyl group, a strong propyl group, an ester group, an amino group, a substituted amino group, a heterocyclic group, etc. Is considered.
- the anion as a counter ion of the quaternary amine salt may be various, and can be a pharmacologically acceptable anion.
- a halogen ion may be an inorganic acid ion such as a sulfate ion, an organic acid ion, or a complex ion.
- the fullerene constituting the carbon class evening skeleton in the fullerene derivative of the invention of this application is also C 7 including C 60 .
- Higher order fullerene such as C 8 2 may also be used.
- the anti-hepatitis C virus agent or anti-HIV agent of the invention of this application may contain one or more of the above-mentioned fullerene derivatives and quaternary amine salts as active ingredients. it can.
- the side chain R and the number of bonds n can be varied by changing the type of aldehyde (RCHO) variously or by changing the ratio of the reaction raw materials.
- N-methylglycine and various aldehydes are dissolved in toluene and heated in an argon stream to obtain an N-methylpyrrolidine derivative. Adjust the reaction time and amount of reagents according to the number of substituents of the required derivative.
- the product is purified on a silica gel column. Next, it is heated at room temperature or in methyl iodide. In this way, derivatives (2-alkyl-N, N-dimethylpyrrolidinium derivatives) having various alkyl substituents (R) and quaternary amino salts thereof can be obtained.
- R 2 H and R 4 is H (compound 2) C 4 H 9 (compound 3), C 6 H 13 (compound 4), C 9 H 19 (compound) 5) Fullerene derivatives of Compound 9 and Compound 12 are synthesized. These have been confirmed to dissolve 5 mM or more in DMSO.
- N-decylglycine and formaldehyde are dissolved in toluene and heated under an argon stream to obtain an N-decylpyrrolidine derivative. Adjust the reaction time and amount of reagents according to the number of derivatives n required. The product is purified on a silica gel column. Next, (N-decyl-N-methylpyrrolidinium derivative) can be obtained by heating at room temperature or in methyl iodide. For example, specifically, compound 6 as described below is synthesized.
- ⁇ A> That is, according to the following reaction formula, first, C 60 , cetyl bromomalonate and sodium hydride are added to toluene, and the mixture is stirred under an argon stream to obtain a cetyl malonate derivative. Adjust the reaction time and reagent amount according to the number of derivatives n required. The product is purified on a silica gel column. Next, the malonate derivative (carboxyl derivative 1) is obtained by adding the jetted malonate derivative and sodium hydride to the toluene and immediately adding methanol after heating to reflux.
- R 3 , R 4 , R 6 may be similar to R 7, reference numeral R 1 0 is a hydrocarbon chain, for example may have the same substituent groups which via a heteroatom such as oxygen atom or nitrogen atom May be combined. It can be a linear or branched hydrocarbon, for example an alkyl chain. For example, a range of about 1 to L 6 is considered as the carbon number of the hydrocarbon chain.
- R 1 1 R 1 2 and R 13 represent hydrocarbon groups that may have a substituent, and the same as those described above can be considered.
- the fullerene strength lpoxyl derivative may be used as a pharmacologically acceptable salt.
- the form of the drug of the invention of this application is not particularly limited.
- tablets, granules, fine granules, pills, powders, capsules, troches, chewables, etc. for external use It may be a liquid preparation such as a jelly-like agent, a thickener, an elixir, a syrup, a suspension, an emulsion, an injection or an infusion.
- conventional carrier components can be used depending on the kind of preparation.
- conventional ingredients for example, sugars such as starch, lactose, sucrose, mannitol, corn starch, excipients such as crystalline cellulose, carboxymethylcellulose, light anhydrous anhydride, etc., polyvinyl Alcohol, polyvinyl pyrrolidone, polyvinyl ether, ethyl cellulose, gum arabic, tragacanth, gelatin, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, calcium citrate, dextrin, pectin, etc .; magnesium stearate, calcium stearate, Lubricants such as talc, polyethylene glycol, colloidal silica; starch, carboxymethyl cellulose, carboxymethylcellulose calcium, croscarmellose sodium Collapse ⁇ , collapse ⁇ , humectants, and surfactants can be used for.
- preservatives for the above-mentioned solid preparations and liquids, preservatives, solubilizers, emulsifiers, dispersants, thickeners, plasticizers, adsorbents, fragrances, coloring agents, flavoring agents, sweeteners, preservatives as necessary.
- Antioxidants can be used.
- the anti-hepatitis C virus agent and anti-HIV agent of the invention of this application are commonly used for mixing, kneading, granulation, tableting, coating, sterilization, emulsification, etc., depending on the form of the preparation. It can manufacture by the method of. Regarding the manufacture of the drug product, you can refer to each section of the Japanese Pharmacopoeia General Rules for Drug Preparation.
- medical agent of invention of this application may contain the said fullerene derivative as an active ingredient, it may contain the other medicinal active ingredient.
- Aluminum oxide >> Sodium hydrogen carbonate coprecipitation product, Magnesium hydroxide / magnesium carbonate coprecipitation product, Magnesium metasilicate aluminate, Dihydroxyaluminum aminoacetate, etc.
- gastric agents such as wikipedia, carnitine chloride, muglutamine succinate, betaine hydrochloride, pecanic nechol, pancreatin, pepsin, limonase hydrochloride, cholic acid, bile powder, dehydrocholate Intestinal preparations such as erythrocytes, red buds, peanuts, cupais, kemeishi, gennosho, oral peramide, bismuth nitrate, bismuth carbonate, berberine chloride and other antidiarrheal agents, dicyclomine hydrochloride, scopolamine hydrobromide, methylatropine bromide, Contains analgesic and antispasmodic agents such as methyl scopolamine bromide, papaverine hydrochloride, isopropamide iodide, belladonna extract, and lotus extract, and mucosal repair agents such as sucralfate, sulpiride, gefarnate, and te
- the drug of the invention of this application is interferon lipavirin as another anti-hepatitis C virus agent, reverse transcriptase inhibitor azidotimi as another anti-HIV agent It may contain gin, lamivudine and the like, and protease inhibitors isodinavir, saquinavir, and the like.
- the dose of the drug of the invention of this application is not particularly limited, but as a guideline, when administered orally, 0.005 to 5 O mg per kg body weight per day Considering divided doses in a range.
- the fullerene derivative of the invention of this application has low toxicity and is useful as a pharmaceutical agent.
- the inventor of this application synthesizes compounds such as fullerene derivatives and their quaternary ammine salts as active ingredients of the invention of this application exemplified in the following table, and the anti-hepatitis C virus and anti-HIV Activity was evaluated.
- the inhibitory activity was examined using an experimental system (D. Dhanak et al., J. Biol. Chem, 277, 38322-38327 (2002)) for measuring RNA polymerase activity of hepatitis C virus.
- HIV reverse transcriptase is a kind of RNA polymerase, the inventor examined its inhibitory activity.
- the results are illustrated in Table 2. It is confirmed that the active ingredient of the invention of this application inhibits reverse transcriptase.
- the reverse transcriptase inhibitor A Z T used as an anti-AIDS agent is a nucleobase derivative, and the invention of this application provides a new reverse transcriptase inhibitor different from the conventional one.
- anti-HIV agents are often used together with anti-HIV agents because HIV infection destroys the immune system, making it susceptible to various infectious diseases and leading to death.
- the fullerene derivative of the invention of this application is superior to other anti-HIV drugs because of its antibacterial activity.
- the antibacterial activity of the active ingredient of the invention of this application as described above is shown in the table.
- Table 3 shows the minimum concentration (MIC) of each fullerene derivative that inhibits the growth of various gram-positive bacteria compared to vancomycin (VCM) (low concentration (small number)).
- VCM vancomycin
- Each fullerene derivative was dissolved in DMS0 and added to the culture medium of the fungus.
- Vancomycin is an antibacterial agent used in drug-resistant bacteria (mesitillin-resistant bacteria, MRSA), which is currently a problem.
- Compound 2 positional isomers, 2t-2, 2t-3, 2t-4, and compounds 3 and 4 showed effective antibacterial activity, but compounds 3 and 4 were more active than compound 2 positional isomers. It was a little low.
- VRE E.faecium vanA
- a novel hepatitis C virus RNase polymerase inhibitor activity or HIV reverse transcriptase inhibitory activity comprising fullerene derivatives and fullerene carboxyl derivatives as active ingredients. And an anti-HIV agent having sex.
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Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/548,626 US7956079B2 (en) | 2003-03-10 | 2004-03-10 | Antihepatitis C virus agent and anti-HIV agent |
CA2518766A CA2518766C (en) | 2003-03-10 | 2004-03-10 | Anti-hepatitis c virus agents and anti-hiv agents |
DE602004021175T DE602004021175D1 (de) | 2003-03-10 | 2004-03-10 | Antihepatitis-c-virus-mittel und anti-hiv-mittel |
AT04719087T ATE431737T1 (de) | 2003-03-10 | 2004-03-10 | Antihepatitis-c-virus-mittel und anti-hiv-mittel |
EP04719087A EP1607091B1 (en) | 2003-03-10 | 2004-03-10 | Antihepatitis c virus agent and anti-hiv agent |
US12/956,505 US8344017B2 (en) | 2003-03-10 | 2010-11-30 | Anti-hepatitis C virus agents and anti-HIV agents |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2003063740 | 2003-03-10 | ||
JP2003-63740 | 2003-03-10 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/548,626 A-371-Of-International US7956079B2 (en) | 2003-03-10 | 2004-03-10 | Antihepatitis C virus agent and anti-HIV agent |
US12/956,505 Division US8344017B2 (en) | 2003-03-10 | 2010-11-30 | Anti-hepatitis C virus agents and anti-HIV agents |
Publications (1)
Publication Number | Publication Date |
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WO2004080453A1 true WO2004080453A1 (ja) | 2004-09-23 |
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PCT/JP2004/003080 WO2004080453A1 (ja) | 2003-03-10 | 2004-03-10 | 抗c型肝炎ウイルス剤と抗hiv剤 |
Country Status (6)
Country | Link |
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US (2) | US7956079B2 (ja) |
EP (1) | EP1607091B1 (ja) |
AT (1) | ATE431737T1 (ja) |
CA (1) | CA2518766C (ja) |
DE (1) | DE602004021175D1 (ja) |
WO (1) | WO2004080453A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2494991A1 (en) | 2007-05-04 | 2012-09-05 | Vertex Pharmaceuticals Incorporated | Combination therapy for the treatment of HCV infection |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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US20100048524A1 (en) | 2008-03-14 | 2010-02-25 | Angela Brodie | Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity |
RU2533232C2 (ru) * | 2012-07-20 | 2014-11-20 | Федеральное государственное бюджетное учреждение "Научно-исследовательский институт вирусологии им. Д.И. Ивановского" Министерства здравоохранения и социального развития Российской Федерации (ФГБУ "НИИ вирусологии им. Д.И. Ивановского" Минздравсоцразвития России | Применение поликарбоксильного производного фуллерена в качестве микробицидного противовирусного средства |
US10358419B2 (en) * | 2015-03-12 | 2019-07-23 | The Board Of Regents Of The University Of Texas System | 1,3-dipolar [70]fulleropyrrolidinium iodide derivatives |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08503693A (ja) * | 1992-09-08 | 1996-04-23 | ヘキスト・アクチェンゲゼルシャフト | 新規なフラレン誘導体、それらの合成方法及びそれらの利用 |
JP2000514412A (ja) * | 1996-06-03 | 2000-10-31 | エフ・ホフマン―ラ ロシュ アーゲー | 神経毒性損傷の処置のためのバックミンスターフラーレンの使用 |
JP2001302630A (ja) * | 2000-03-06 | 2001-10-31 | Long Y Chiang | E異性体フラーレン誘導体 |
US20030036562A1 (en) * | 2001-05-11 | 2003-02-20 | Schinazi Raymond F. | Water-soluble dendrimeric fullerene as anti-HIV therapeutic |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2673179B1 (fr) * | 1991-02-21 | 1993-06-11 | Oreal | Ceramides, leur procede de preparation et leurs applications en cosmetique et en dermopharmacie. |
US5528599A (en) | 1993-08-30 | 1996-06-18 | Motorola, Inc. | Method and apparatus of combining signals in a digital pipelined signal adder |
DE4338672A1 (de) * | 1993-11-12 | 1995-08-17 | Hoechst Ag | Amino-ureido- und thioureido-fulleren-Derivate und Verfahren zu deren Herstellung |
JP3506754B2 (ja) | 1994-03-09 | 2004-03-15 | 三菱化学株式会社 | 炭素クラスター誘導体 |
US6162926A (en) * | 1995-07-31 | 2000-12-19 | Sphere Biosystems, Inc. | Multi-substituted fullerenes and methods for their preparation and characterization |
US5648523A (en) | 1995-10-26 | 1997-07-15 | Chiang Long Y | Fullerene derivatives as free-radical scavengers |
US6265443B1 (en) | 1996-06-03 | 2001-07-24 | Washington University | Method for treating neuronal injury with carboxyfullerene |
JP4253858B2 (ja) | 1998-03-12 | 2009-04-15 | 生化学工業株式会社 | フラーレン誘導体およびその製造方法 |
-
2004
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- 2004-03-10 CA CA2518766A patent/CA2518766C/en not_active Expired - Fee Related
- 2004-03-10 WO PCT/JP2004/003080 patent/WO2004080453A1/ja active Application Filing
- 2004-03-10 AT AT04719087T patent/ATE431737T1/de not_active IP Right Cessation
- 2004-03-10 US US10/548,626 patent/US7956079B2/en not_active Expired - Fee Related
- 2004-03-10 DE DE602004021175T patent/DE602004021175D1/de not_active Expired - Lifetime
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH08503693A (ja) * | 1992-09-08 | 1996-04-23 | ヘキスト・アクチェンゲゼルシャフト | 新規なフラレン誘導体、それらの合成方法及びそれらの利用 |
JP2000514412A (ja) * | 1996-06-03 | 2000-10-31 | エフ・ホフマン―ラ ロシュ アーゲー | 神経毒性損傷の処置のためのバックミンスターフラーレンの使用 |
JP2001302630A (ja) * | 2000-03-06 | 2001-10-31 | Long Y Chiang | E異性体フラーレン誘導体 |
US20030036562A1 (en) * | 2001-05-11 | 2003-02-20 | Schinazi Raymond F. | Water-soluble dendrimeric fullerene as anti-HIV therapeutic |
Non-Patent Citations (7)
Title |
---|
BOSI S. ET AL: "Antimycobacterial activity of ionic fullerene derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 10, no. 10, 2000, pages 1043 - 1045, XP004204601 * |
BOSI S. ET AL: "Synthesis and Anti-HIV Properties of New Water-Soluble Bis-functionalized[60]fullerene Derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 13, no. 24, 2003, pages 4437 - 4440, XP002979769 * |
GHARBI N. ET AL: "Chromatographic and electrophoretic profiles of two acidic water-soluble fullerene derivatives", PROCEEDINGS - ELECTROCHEMICAL SOCIETY, vol. 2002-12, 2002, pages 443 - 450, XP002979770 * |
GHARBI N. ET AL: "Chromatographic Separation and Identification of a Water-Soluble Dendritic Methano[60]fullerene Octadecaacid", ANALYTICAL CHEMISTRY, vol. 75, no. 16, 2003, pages 4217 - 4222, XP002979771 * |
HUANG Y.-L. ET AL: "Blockage of apoptotic signaling of transforming growth factor-beta in human hepatoma cells by carboxyfullerene", EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 254, no. 1, 1998, pages 38 - 43, XP002979773 * |
MASHINO T. ET AL: "Antibacterial and Antiproliferative Activity of Cationic Fullerene Derivatives", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 13, no. 24, 2003, pages 4395 - 4397, XP002979768 * |
SCHUSTER D. ET AL: "Evaluation of the anti-HIV potency of a water-soluble dendrimeric fullerene", PROCEEDINGS - ELECTROCHEMICAL SOCIETY, vol. 2000-11, 2000, pages 267 - 270, XP002979772 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2494991A1 (en) | 2007-05-04 | 2012-09-05 | Vertex Pharmaceuticals Incorporated | Combination therapy for the treatment of HCV infection |
Also Published As
Publication number | Publication date |
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US20070037867A1 (en) | 2007-02-15 |
ATE431737T1 (de) | 2009-06-15 |
EP1607091B1 (en) | 2009-05-20 |
EP1607091A1 (en) | 2005-12-21 |
US8344017B2 (en) | 2013-01-01 |
DE602004021175D1 (de) | 2009-07-02 |
EP1607091A4 (en) | 2006-05-17 |
US7956079B2 (en) | 2011-06-07 |
US20110071202A1 (en) | 2011-03-24 |
CA2518766A1 (en) | 2004-09-23 |
CA2518766C (en) | 2012-07-03 |
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