WO1992000078A1 - Agents antiviraux contenant de l'heteropolytungstate - Google Patents

Agents antiviraux contenant de l'heteropolytungstate Download PDF

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Publication number
WO1992000078A1
WO1992000078A1 PCT/AU1991/000280 AU9100280W WO9200078A1 WO 1992000078 A1 WO1992000078 A1 WO 1992000078A1 AU 9100280 W AU9100280 W AU 9100280W WO 9200078 A1 WO9200078 A1 WO 9200078A1
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WIPO (PCT)
Prior art keywords
compound
cptipw
formula
cptip
cpe
Prior art date
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PCT/AU1991/000280
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English (en)
Inventor
Helmut Weigold
George Holan
Sebastian Mario Marcuccio
Christopher John Birch
Ian David Gust
Original Assignee
Commonwealth Scientific And Industrial Research Organisation
Fairfield Hospital Board
Macfarlane Burnet Centre For Medical Research Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Application filed by Commonwealth Scientific And Industrial Research Organisation, Fairfield Hospital Board, Macfarlane Burnet Centre For Medical Research Limited filed Critical Commonwealth Scientific And Industrial Research Organisation
Priority to JP3510909A priority Critical patent/JPH06501451A/ja
Priority to BR919106596A priority patent/BR9106596A/pt
Priority to CS923962A priority patent/CZ396292A3/cs
Priority to AU80064/91A priority patent/AU647800B2/en
Priority to HU9204137A priority patent/HUT63332A/hu
Publication of WO1992000078A1 publication Critical patent/WO1992000078A1/fr
Priority to NO92924966A priority patent/NO924966L/no
Priority to FI925908A priority patent/FI925908A/fi

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • 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
    • A61K31/28—Compounds containing heavy metals
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/295—Iron group metal compounds
    • 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
    • A61K31/28—Compounds containing heavy metals
    • A61K31/315—Zinc compounds
    • 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
    • A61K31/66—Phosphorus compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/42—Phosphorus; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B25/00—Phosphorus; Compounds thereof
    • C01B25/16—Oxyacids of phosphorus; Salts thereof
    • C01B25/26—Phosphates
    • C01B25/45—Phosphates containing plural metal, or metal and ammonium
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B25/00—Phosphorus; Compounds thereof
    • C01B25/16—Oxyacids of phosphorus; Salts thereof
    • C01B25/26—Phosphates
    • C01B25/45—Phosphates containing plural metal, or metal and ammonium
    • C01B25/451—Phosphates containing plural metal, or metal and ammonium containing metal and ammonium

Definitions

  • the present invention relates to heteropolytungstates and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions containing them, and to the use of these compounds in therapy, particularly for the treatment or prophylaxis of certain viral infections, for example retroviral infections such as Acquired Immune Deficiency Syndrome (AIDS).
  • AIDS Acquired Immune Deficiency Syndrome
  • Lymphotropic Virus III (HLTV-III)] is a member of this family. This virus will be identified herein as HIV. Infection with HIV is associated with depletion of T4 lymphocytes, brain disease, and several types of cancer including Kaposis sarcoma. Patients infected with the virus also have a high incidence of opportunistic infections and a significantly reduced life span.
  • Another virus within the same family is the Human T-cell Lymphotropic Virus Type 1 (HLTV-1) the causative agent of Adult T-cell leukaemia, an infection with high mortality occurring in a distinctive geographical pattern.
  • Retroviridae All members of the family Retroviridae possess a unique enzyme, reverse transcriptase, which is necessary for their replication. Because this enzyme is not normally present in uninfected cells, it is considered a target for antiviral drugs.
  • Another virus utilising reverse transcriptase during replication is the Hepatitis B Virus (HBV). HBV causes widespread morbidity and mortality and is the main cause of primary hepatocellular carcinoma in individuals who are chronic carriers of the virus. Because of the common evolutionary origin of HBV and the retroviruses, treatment of HBV-infected individuals with the same regimen of drugs proposed herein for the treatment of patients infected with HIV could be possible.
  • HBV Hepatitis B Virus
  • Heteropolytungstate compounds have been known for over 100 years. Most of their applications stem from their redox chemistry and also their high ionic weights and charges. Their redox chemistry has led to their most common use: catalysts for the oxidation of organic substrates such as, for example, propylene to acrylic acid, ethylene to acetaldehyde. In the biological field heteropolytungstates have found use as electron dense stains for electron microscopy, as analytical reagents for proteins and a few have also been shown to inhibit viral DNA and RNA polymerases (J.C. Chermann et al., Biochem. Biophys. Res. Comm., 1975, 65, 1229; M.
  • HPA-23 has since been shown to be inactive in other in vitro screens and in subsequent clinical trials (J. Balzarini et al., Int. J. Cancer, 1986, 37, 451; M. Burgard,ef al., AIDS, 1989, 3, 665).
  • the compounds of this invention are in general less toxic and more active than HPA-23 with antiviral indexes >20 and generally >50 and are active in all cell lines tested to date.
  • Therapeutic index is defined as the ratio of the dose which is toxic to 50% of the test cells to the dose required to reduce the virus count by 50%
  • the heteropolytungstates of this invention are based on Keggin-type and
  • Dawson-type structures carrying either one or three vacancies. These vacancies are created by extraction of WO 4+ or W 3 O 6 6+ from the PW 12 O 40 3- (Keggin) or P 2 W 18 O 66 6- (Dawson) structure. Isomers of these unsaturated (lacunary) polyanions are possible, a consequence of the location of the vacancy.
  • the position of the vacancy in P 2 W 17 O 611 0- is defined by the prefix ⁇ 1- for a belt vacancy o ⁇ ⁇ 2- for a cap vacancy.
  • the prefix ⁇ - or ⁇ - refers to isomerisation associated with the relative rotation of the W 3 triad cap.
  • PW9O 34 9- the vacancy is found in either of two locations.
  • P 2 W 15 O 56 12- ligand to the set of four coplanar copper atoms is similar to that found in the corresponding PW 9 O 34 9- containing compounds.
  • the corresponding PW 9 O 34 9- containing compounds the corresponding PW 9 O 34 9- containing compounds.
  • P 2 W 15 O 56 12- polyanion is formed from a-P 2 W 18 O 62 6- by removal of one
  • edge-sharing cap (containing three tungsten atoms).
  • heteropolytungstates derived from Keggin and Dawson type structures carrying either one or three vacancies as described above are inhibitors of HIV infection.
  • the present invention provides a method for the treatment or prophylaxis of a retrovirus-associated infection which involves the use of a heteropolytungstate compound of the general formulae I having a therapeutic index (as hereinbefore defined) of 50 or greater:
  • M is Co, Fe, Zn, FeOA, FeO 1/2 ;
  • Cp represents an optionally substituted cyclopentadienyl residue
  • A is a monovalent or divalent cation or mixture of such cations; m is the number of cations necessary for electrical neutrality of the molecule.
  • the compounds of the invention are polyanions with associated cations (A) for electrical neutrality. They crystallise with a variable number of molecules of water of crystallisation (n) dependent upon the conditions of product recovery and subsequent treatment; all such hydrate forms fall within the scope of this invention.
  • divalent cations or a mixture of monovalent and divalent cations, are present then a lesser number will be sufficient for electrical neutrality and m will be smaller.
  • Preferred cations are sodium, potassium, lithium, ammonium,
  • alkylammonium, cationic alkali metal crown ether complexes, magnesium, or calcium alkylammonium, cationic alkali metal crown ether complexes, magnesium, or calcium.
  • substituents in relation to the cyclopentadienyl residue, means that the residue may contain one or more substituents. Suitable substituents will be chosen on the basis of the known chemistry of cyclopentadienyl-titanium complexes. In general, substituents will be selected on the basis that:
  • a pharmaceutically acceptable derivative is meant any pharmaceutically acceptable salt, or any other compound which, upon administration to the recipient, is capable of providing (directly or indirectly) a heteropolytungstate of the general formula I, or an antivirally active metabolite or residue thereof
  • the compounds according to the invention may also be used in the manufacture of a medicament for the treatment or prophylaxis of a retrovirus-associated infection.
  • the present invention provides a pharmaceutical composition for the treatment or prophylaxis of a retrovirus-associated infection, which comprises an effective amount of a compound of the general formula I, in association with a pharmaceutically acceptable carrier or diluent.
  • the present invention also extends to a method for the treatment or prophylaxis of a retrovirus associated infection, which comprises administering to a patient in need of such treatment or prophylaxis an effective amount of a compound of the general formula I.
  • Examples of compounds of Formula 1 which fall within the ambit of the present invention include the following 2 :
  • 18-C6K means compounds containing K + complexed by the cyclic polyether 18-Crown-6 1.
  • the invention also provides novel compound according to formula, I and includes the specific compounds listed above, excluding those listed as being known.
  • the compounds according to the invention may be administered for therapy by any suitable route, including oral, rectal, nasal, topical (including buccal and sublingual), vaginal and parenteral (including subcutaneous, intramuscular, intravenous and intradermal).
  • administration will be by the oral route, however it will be appreciated that the preferred route will vary with the condition and age of the recipient, and the nature of the chosen active ingredient.
  • a suitable dose will be in the range of 3.0 to 120 mg per kilogram body weight of the recipient per day, preferably in the range of 6 to 90 mg per kilogram body weight per day and most preferably in the range 15 to 60 mg per kilogram body weight per day.
  • the desired dose is preferably presented as two, three, four, five, six or more sub-doses administered at appropriate intervals throughout the day. These sub-doses may be administered in unit dosage forms, for example, containing 10 to 1500 mg, preferably 20 to 1000 mg, and most preferably 50 to 700 mg of active ingredient per unit dosage form
  • the active ingredient should be administered to achieve peak plasma concentrations of the active compound of from about 0.1 to about 75 mM, preferably about 2 to 50 mM. This may be achieved, for example, by the intravenous injection of a 0.1 to 5% solution of the active ingredient, optionally in saline, or orally administered as a bolus containing about 0.1 to about 100 mg/kg of the active ingredient. Desirable blood levels may be maintained by a continuous infusion to provide about 0.01 to about 5.0 mg/hour by intermittent infusions containing about 0.4 to about 15 mg/mg of the active ingredient. While it is possible for the active ingredient to be administered alone, it is preferable to present it as a pharmaceutical composition.
  • compositions of the present invention comprise at least one compound of general formula (I), together with one or more pharmaceutically acceptably carriers thereof, and optionally other therapeutic agents.
  • Each carrier must be pharmaceutically "acceptable” in the sense of being compatible with the other ingredients of the composition and not injurious to the patient.
  • Compositions include those suitable for oral, rectal, nasal, topical (including buccal and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous and intradermal) administration.
  • the compositions may conveniently be presented in unit dosage form and may be prepared by any methods well known in the art of pharmacy. Such methods include the step of bringing into association the active ingredient with the carrier which constitutes one or more accessory ingredients.
  • compositions are prepared by uniformly and intimately bringing into association the active ingredient with liquid carriers or finely divided solid carriers or both, and then if necessary shaping the product.
  • Compositions of the present invention suitable for oral administration may be presented as discrete units such as capsules, sachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous or non-aqueous liquid; or as an
  • oil-in-water liquid emulsion or a water-in-oil liquid emulsion.
  • the active ingredient may also be presented as a bolus, electuary or paste.
  • a tablet may be made by compression or moulding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as a powder or granules, optionally mixed with a binder (e.g inert diluent, preservative disintegrant (e.g. sodium starch glycollate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose) surface- active or dispersing agent.
  • a binder e.g inert diluent, preservative disintegrant (e.g. sodium starch glycollate, cross-linked povidone, cross-linked sodium carboxymethyl cellulose) surface- active or dispersing agent.
  • Moulded tablets may be made by moulding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.
  • the tablets may optionally be coated or scored and may be formulated so as to provide slow or controlled release of the active ingredient therein using, for example, hydroxypropylmethyl cellulose in varying proportions to provide the desired release profile. Tablets may optionally be provided with an enteric coating, to provide release in parts of the gut other than the stomach.
  • compositions suitable for topical administration in the mouth include lozenges comprising the active ingredient in a flavoured basis, usually sucrose and acacia or tragacanth gum; pastilles comprising the active ingredient in an inert basis such as gelatin and glycerin, or sucrose and acacia gum; and mouthwashes comprising the active ingredient in a suitable liquid carrier.
  • Compositions for rectal administration may be presented as a suppository with a suitable base comprising, for example, cocoa butter or a salicylate.
  • compositions suitable for vaginal administration may be presented as pessaries, tampons, creams, gels, pastes, foams or spray formulations containing in addition to the active ingredient such carriers as are known in the art to be appropriate.
  • compositions suitable for parenteral administration include aqueous and non-aqueous isotonic sterile injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the composition isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may include suspending agents and thickening agents.
  • the compositions may be presented in unit-dose or multi-dose sealed containers, for example, ampoules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, for example water for injections, immediately prior to use.
  • Extemporaneous injection solutions and suspensions may be prepared from sterile powders, granules and tablets of the kind previously described.
  • Preferred unit dosage compositions are those containing a daily dose or unit, daily sub-dose, as herein above recited, or an appropriate fraction thereof, of an active ingredient.
  • the compounds according to the invention may also be presented for use in the form of veterinary compositions, which may be prepared, for example, by methods that are conventional in the art. Examples of such veterinary compositions include those adapted for:
  • oral administration external application, for example drenches (e.g. aqueous or non-aqueous solutions or suspensions); tablets or boluses; powders, granules or pellets for admixture with feed stuffs; pastes for application to the tongue;
  • drenches e.g. aqueous or non-aqueous solutions or suspensions
  • tablets or boluses e.g. aqueous or non-aqueous solutions or suspensions
  • pastes for application to the tongue for example drenches (e.g. aqueous or non-aqueous solutions or suspensions); tablets or boluses; powders, granules or pellets for admixture with feed stuffs; pastes for application to the tongue;
  • parenteral administration for example by subcutaneous, intramuscular or intravenous injection, e.g. as a sterile solution or suspension; or (when appropriate) by intramammary injection where a suspension or solution is introduced into the udder via the teat;
  • topical application e.g. as a cream, ointment or spray applied to the skin;
  • the administered ingredients may also be used in therapy in conjunction with other medicaments or in conjunction with other immune modulating therapy including bone marrow or lymphocyte transplants or medications such as levamisol or thymosin which would increase lymphocyte numbers and/or function as is appropriate.
  • compositions of this invention may include other agents conventional in the art having regard to the type of composition in question, for example, those suitable for oral administration may include such further agents as sweeteners, thickeners and flavouring agents.
  • the infra-red spectrum of the compound in KBr is characterized by a triplet between 1040-1080 cm -1 (phosphate stretches), and strong bands at 947, 873, 809 and 724 cm -1 , presumably arising from W-O stretches and also perhaps Fe-O stretching vibrations which would be expected to lie within this region (see D. M. Kurtz, Jr. in Chem. Rev. 1990, 90, 585-606 ).
  • the Na and NH 4 compounds can be obtained as long, thin, neadle-like crystals, greenish in color. Air drying, especially in the case of the Na compound, causes the crystals to collapse.
  • the Na, Li and NH 4 salts are more readily soluble in water than either the
  • the potassium salt of this compound is obtained as a side product in the synthesis of K 10 [Co 4 (H 2 O) 2 (PW 9 O 34 ) 2 ].H 2 O by the method of H.T. Evans et al . Isolation of the crude K salt was as described in the preparation of
  • the compounds were prepared by the procedure of R.G. Finke et al.
  • a-K 6 P W 18 O 62 - was obtained by the slow addition of a near theoretical amount of a 1M solution of KHCO 3 to ⁇ , ⁇ -K6P 2 W 18 O 62, reacidifying the reaction solution and precipitating with KCl.
  • the potassium salt was converted to the sodium one using NaClO 4 and the trivacant polyanion salt Na 12 P 2 W 15 O 56 .18H 2 O was obtained on raising the reaction solution pH to 9 with Na 2 CO 3 as described by R.G. Finke et al. EXAMPLE OF COMPLEXING OF POLYANION WITH A DIVALENT
  • the substituted cyclopentadienyl compounds were obtained by Keana et al from ( ⁇ 5 -C 5 H 4 R)Ti(NMe 2 ) 3 and ⁇ 2 -K 10 P 2 W 17 O 61 in DMF/benzene and adding a little aqueous acid during the reaction.
  • organometallic is added to the reaction solution at a rate commensurate with the expulsion of organic solvent from the reaction solution to minimize precipitation of heteropolytungstate.
  • a flow of gas through the solution can be used to accellerate the rate of organic solvent evaporation.
  • an orange coloured solution is obtained which may contain a little precipitate.
  • Product purification is effected by either decanting or filtering the reaction solution at room temperature onto an alumina column (For example, Merck, Type 1077, 50-75g, washed with 1M sodium acetate solution acidified with acetic acid to around pH 5.6, and then water) and eluted with water.
  • alumina column For example, Merck, Type 1077, 50-75g, washed with 1M sodium acetate solution acidified with acetic acid to around pH 5.6, and then water
  • a solid product is obtained, which is collected, washed with cold water and re crystallized from water (ca. 75°, 1g product in 7-8ml water. The orange crystals are collected and air dried. Yield (not optimized) 7-8g.
  • the product is readily soluble in DMSO and hot water, sparingly in cold water.
  • Alkali metal salts of the heteropolyanion are obtained by eluting the reaction product from the alumina column with the required alkali metal acetate solution (ca. pH 5.6) and precipitating the product with ethanol followed by
  • active ingredient means a compound of formula (I) or a pharmaceutically acceptable derivative thereof.
  • the anti-HIV activity of compounds 1 to 21 of Example 1 has been assessed by the following test: Approximately one million human continuous lymphocytes (MT2) were exposed to each test compound at concentrations previously demonstrated to be non-toxic to MT2 cells (that is no drug related effect on cell numbers or cell morphology) for 2 hours at 37°C. They were then infected with Human Immunodeficiency Virus (HIV strain 237288, 2000-10,000 TCID 50 per million MT2 cells) and cultured at 37°C in the presence of the test compound. Fresh amounts of test compound were added at the appropriate dilution 3 days later. Two types of controls were run with each batch of tests:
  • test compounds were also assessed by degree of the inhibition of reverse transcriptase activity at each concentration. After 5-7 days incubation as described above, supernatant fluids from each flask were removed and tested for virion associated reverse transcriptase (RT) activity using a standard method.
  • RT virion associated reverse transcriptase
  • formulation A may be prepared by wet granulation of the ingredients with a solution of povidone, followed by addition of magnesium stearate and compression.
  • formulation B may be prepared by direct compression of the admixed ingredients.
  • This formulation may be prepared by wet granulation of the ingredients (below) with a solution of povidone followed by the addition of magnesium stearate and compression.
  • a capsule formulation may be prepared by admixing the ingredients of Formulation
  • Formulation B (infra) may be prepared in a similar manner.
  • the following controlled release capsule formulation may be prepared by extruding ingredients (a), (b) and (c) using an extruder, followed by spheronisation of the extrudate and drying. The dried pellets may then be coated with
  • the active ingredient may be dissolved in most of the water (35°-40°C) and the pH adjusted to between 5.0 and 7.0 with the hydrochloric acid or the sodium hydroxide as appropriate.
  • the batch may then be made up to volume with the water and filtered through a sterile micropore filter into a sterile 10 ml amber glass vial (type 1) and sealed with sterile closures and overseals.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Virology (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composés d'hétéropolytungstate des formules générales (I) où M représente Co, Fe, Zn, FeOA, FeO1/2; Cp représente un résidu de cyclopentadiényle éventuellement substitué; A représente un cation univalent ou bivalent ou un mélange de tels cations; m représente le nombre de cations nécessaires à la neutralité électrique de la molécule; ou des dérivés pharmaceutiquement acceptables de ces éléments. Des compositions pharmaceutiques ou des méthodes destinées au traitement ou à la prophylaxie d'infections associées aux rétrovirus et préconisant l'utilisation de tels composés sont aussi décrites.
PCT/AU1991/000280 1990-06-29 1991-06-28 Agents antiviraux contenant de l'heteropolytungstate WO1992000078A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP3510909A JPH06501451A (ja) 1990-06-29 1991-06-28 ヘテロポリタングステン酸塩を含む抗ウイルス剤
BR919106596A BR9106596A (pt) 1990-06-29 1991-06-28 Processo para o tratamento ou profilaxia de uma infeccao associada com retrovirus,uso,composicao farmaceutica para o tratamento ou profilaxia de uma infeccao associada com retrovirus,e,composto
CS923962A CZ396292A3 (en) 1990-06-29 1991-06-28 Pharmaceutical preparation for treating and prophylaxis of infection
AU80064/91A AU647800B2 (en) 1990-06-29 1991-06-28 Antiviral agents containing heteropolytungstate
HU9204137A HUT63332A (en) 1990-06-29 1991-06-28 Anti-viral materials containing hetero-poly-tungstate
NO92924966A NO924966L (no) 1990-06-29 1992-12-22 Antivirale midler som inneholder heteropolywolframat
FI925908A FI925908A (fi) 1990-06-29 1992-12-28 Antivirala medel innehaollande heteropolyvolframat

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPK091790 1990-06-29
AUPK0917 1990-06-29

Publications (1)

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WO1992000078A1 true WO1992000078A1 (fr) 1992-01-09

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PCT/AU1991/000280 WO1992000078A1 (fr) 1990-06-29 1991-06-28 Agents antiviraux contenant de l'heteropolytungstate

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EP (1) EP0536224A1 (fr)
JP (1) JPH06501451A (fr)
AU (1) AU647800B2 (fr)
BR (1) BR9106596A (fr)
CA (1) CA2086263A1 (fr)
CZ (1) CZ396292A3 (fr)
FI (1) FI925908A (fr)
HU (1) HUT63332A (fr)
NO (1) NO924966L (fr)
WO (1) WO1992000078A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999004803A1 (fr) * 1997-07-24 1999-02-04 Biomolecular Research Institute Limited Composes d'heteropolytungstate utilises comme inhibiteurs de l'angiogenese
WO1999021569A1 (fr) * 1997-10-24 1999-05-06 Starpharma Limited Composition antifilovirale a base de polyoxometallates

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9828020D0 (en) * 1998-12-18 1999-02-10 Bp Chem Int Ltd Synthesis of heteropolyacids

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU4316889A (en) * 1988-09-22 1990-04-18 Craig L. Hill Polyoxometallate compounds as antiviral agents
AU5141090A (en) * 1989-03-17 1990-09-20 Johnson Matthey Public Limited Company Keggin ion compounds in HIV treatment
AU7094491A (en) * 1990-02-15 1991-08-22 Johnson Matthey Public Limited Company Improvements in chemical compounds

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU4316889A (en) * 1988-09-22 1990-04-18 Craig L. Hill Polyoxometallate compounds as antiviral agents
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WO1999021569A1 (fr) * 1997-10-24 1999-05-06 Starpharma Limited Composition antifilovirale a base de polyoxometallates

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NO924966L (no) 1993-02-17
CA2086263A1 (fr) 1991-12-30
CZ396292A3 (en) 1994-01-19
AU647800B2 (en) 1994-03-31
HUT63332A (en) 1993-08-30
HU9204137D0 (en) 1993-03-29
FI925908A0 (fi) 1992-12-28
FI925908A (fi) 1992-12-28
EP0536224A1 (fr) 1993-04-14
NO924966D0 (no) 1992-12-22
BR9106596A (pt) 1993-06-01
JPH06501451A (ja) 1994-02-17
AU8006491A (en) 1992-01-23

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