EP1115388A1 - Utilisation de composes organophosphores pour la production de medicaments pour le traitement therapeutique et prophylactique d'infections ou en tant que fongicide, bactericide ou herbicide pour vegetaux - Google Patents

Utilisation de composes organophosphores pour la production de medicaments pour le traitement therapeutique et prophylactique d'infections ou en tant que fongicide, bactericide ou herbicide pour vegetaux

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Publication number
EP1115388A1
EP1115388A1 EP99969332A EP99969332A EP1115388A1 EP 1115388 A1 EP1115388 A1 EP 1115388A1 EP 99969332 A EP99969332 A EP 99969332A EP 99969332 A EP99969332 A EP 99969332A EP 1115388 A1 EP1115388 A1 EP 1115388A1
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EP
European Patent Office
Prior art keywords
substituted
viruses
unsubstituted
genus
quinone
Prior art date
Legal status (The legal status 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 status listed.)
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Application number
EP99969332A
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German (de)
English (en)
Inventor
Hassan Jomaa
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Bioagency AG
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Hassan Jomaa
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Filing date
Publication date
Application filed by Hassan Jomaa filed Critical Hassan Jomaa
Publication of EP1115388A1 publication Critical patent/EP1115388A1/fr
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Classifications

    • 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
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
    • A01N57/20—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing acyclic or cycloaliphatic radicals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P13/00—Herbicides; Algicides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • 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
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • 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
    • 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
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • organophosphorus compounds for the manufacture of medicaments for the therapeutic and prophylactic treatment of infections or as a fungicide.
  • the invention relates to the use of organophosphorus compounds and their salts, esters and amides for the production of medicaments for the therapeutic and prophylactic treatment of infections in humans and animals which are caused by viruses, bacteria, fungi and parasites, and their use as a fungicide, bactericide and herbicide in plants.
  • the organophosphorus compounds comprise phosphinoyl derivatives and phosphinic acid derivatives.
  • the object of the present invention is therefore to provide a substance which can be used in infections by viruses, bacteria, fungi and parasites in humans and animals and as a fungicide, bactericide and herbicide in plants and which fulfills the conditions specified above.
  • This object is achieved in a completely surprising manner by the group of substances defined in claim 1.
  • This group of substances shows both an anti-infectious effect against viruses, certain bacteria, fungi, single and multicellular parasites as well as a fungicidal, bactericidal and herbicidal activity in plants.
  • organophosphorus compounds used according to the invention correspond to the general formula (I):
  • Ri and R 2 are the same or different and are selected from the group consisting of Hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted, unsubstituted aralkyl, substituted, unsubstituted and unsubstituted OX !
  • Xi and X 2 may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl , substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical,
  • A is selected from the group consisting of an alkylene radical, an alkenylene radical and a hydroxyalkylene radical,
  • R 3 is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted Cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen,
  • R is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted alkyl, substituted and unsubstituted, substituted and unsubstituted heterocyclic radical, halogen, OX *, where XL »is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxylalkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted Alkenyl, substituted and unsubstituted alkynyl
  • X ⁇ is selected from the group consisting of hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic radical;
  • R 2 , R 3 , R4 and A have the same meaning as in formula (I).
  • A is particularly preferably a chain of three carbon atoms which connects the nitrogen atom to the phosphorus atom.
  • the three-link chain can be substituted.
  • R acyl, in particular formyl or acetyl
  • R 3 hydrogen, methyl or ethyl
  • A alkylene, alkenylene or hydroxyalkylene.
  • R 2 formyl or acetyl
  • A propylene, propenylene or hydroxypropylene.
  • Acyl is a substituent derived from an acid, such as from an organic carboxylic acid, carbonic acid, carbamic acid or the thioic acid or imidic acid corresponding to the individual acids above, or from an organic sulfonic acid, these acids each being aliphatic, aromatic and / or heterocyclic Include groups in the molecule as well as carbamoyl or carbamimidoyl.
  • Aliphatic acyl groups are acyl radicals derived from an aliphatic acid, which include the following:
  • Alkanoyl e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl etc.
  • Alkenoyl e.g. acryloyl, methacryloyl, crotonoyl etc.
  • Alkylthioalkanoyl e.g. methylthioacetyl, ethylthioacetyl etc.
  • Alkanesulfonyl e.g. mesyl, ethanesulfonyl, propanesulfonyl, etc.
  • Alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycar- bonyl, butoxycarbonyl, isobutoxycarbonyl etc.
  • Alkyl carbamoyl e.g. methyl carbamoyl etc.
  • N-alkyl thiocarbamoyl e.g. (N-methyl) thiocarbamoyl etc.
  • Alkyl carbamimidoyl e.g. methyl carbamimidoyl etc.
  • Alkoxalyl e.g. methoxalyl, ethoxalyl, propoxalyl etc.
  • the aliphatic hydrocarbon part in particular the alkyl group or the alkane radical, can optionally have one or more suitable substituents, such as amino, halogen (for example fluorine, chlorine, bromine, etc.), hydroxy, hydroxyimino, Carboxy, alkoxy (e.g. methoxy, ethoxy, propoxy etc.), alkoxycarbonyl, acylamino (e.g. benzyloxycarbonylamino etc.), acyloxy (e.g. acetoxy, benzoyloxy etc.) and the like; as preferred aliphatic acyl radicals with such substituents are e.g. alkanoyl substituted with amino, carboxy, amino and carboxy, halogen, acylamino or the like.
  • suitable substituents such as amino, halogen (for example fluorine, chlorine, bromine, etc.), hydroxy, hydroxyimino, Carboxy, alkoxy (e.g. methoxy,
  • Aromatic acyl radicals are those acyl radicals which derive from an acid with a substituted or unsubstituted aryl group, where the aryl group can include phenyl, toluyl, xylyl, naphthyl and the like; suitable examples are given below:
  • Aroyl e.g. benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl etc.
  • Aralkanoyl e.g. phenylacetyl etc.
  • Aralkenoyl e.g. cinnamoyl etc.
  • Aryloxyalkanoyl e.g. phenoxyacetyl etc.
  • Arylthioalkanoyl e.g. phenylthioacetyl etc.
  • Arylaminoalkanoyl e.g. N-phenylglycyl, etc.
  • Arenesulfonyl e.g. benzenesulfonyl, tosyl or toluenesulfonyl, naphthalenesulfonyl etc.
  • Aryloxycarbonyl e.g. phenoxycarbonyl, naphthyloxycarbonyl etc.
  • Aralkoxycarbonyl e.g. benzyloxycarbonyl etc.
  • Arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc.
  • Arylglyoxyloyl e.g. phenylglyoxyloyl etc.
  • aromatic hydrocarbon part in particular the aryl radical
  • aliphatic hydrocarbon part in particular the alkane radical
  • suitable substituents such as those which are suitable substituents for the alkyl group or the alkane radical have already been specified.
  • aromatic acyl radicals with special substituents aroyl substituted with halogen and hydroxy or with halogen and acyloxy and substituted with hydroxy, hydroxyimino, dihalogenalkanoyloxyimino Aralkanoyl indicated as well
  • Arylthiocarbamoyl e.g. phenylthiocarbamoyl etc.
  • Arylcarbamimidoyl e.g. phenylcarbamimidoyl etc.
  • a heterocyclic acyl radical is understood to mean an acyl radical which comes from an acid with a heterocyclic group; this includes:
  • Heterocyclic carbonyl in which the heterocyclic radical is an aromatic or aliphatic 5- to 6-membered heterocycle with at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (e.g. thiophenyl, furoyl, pyrrole carbonyl, nicotinoyl etc.);
  • Heterocycle alkanoyl in which the heterocyclic radical is 5- to 6-membered and has at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (for example thiophenyl-acetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino- 4-thiazolyl) -2-methoxyiminoacetyl etc.) and the like.
  • nitrogen, oxygen and sulfur for example thiophenyl-acetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino- 4-thiazolyl) -2-methoxyiminoacetyl etc.
  • heterocyclic acyl groups the heterocycle and / or the aliphatic hydrocarbon portion may optionally have one or more suitable substituents, such as the same ones that have been stated to be suitable for alkyl and alkane groups.
  • Alkyl is a straight or branched chain alkyl radical having up to 9 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like.
  • Hydroxylalkyl is a straight or branched chain alkyl radical with up to 9 carbons, which has at least one hydroxyl group, preferably one or two hydroxyl groups.
  • Alkenyl includes straight-chain or branched-chain alkenyl groups with up to 9 carbon atoms, such as, for example, vinyl, propenyl (for example 1-propenyl, 2-propenyl), 1-methylpropenyl, 2-methylpropenyl, butenyl, 2-ethylpropenyl, pentenyl, hexenyl .
  • Alkynyl includes straight or branched chain alkynyl groups with up to 9 carbon atoms.
  • Cycloalkyl is preferably an optionally substituted C3-C7-cycloalkyl; possible substituents include Alkyl, alkenyl, alkynyl, alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc.), nitro and the like are suitable.
  • Aryl is an aromatic hydrocarbon radical, such as phenyl naphthyl etc., which may optionally have one or more suitable substituents, such as alkyl, alkenyl, alkynyl, alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc.), nitro and the like.
  • suitable substituents such as alkyl, alkenyl, alkynyl, alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc.), nitro and the like.
  • Alkyl includes mono-, di-, triphenylalkyls such as benzyl, phenethyl, benzhydryl, trityl and the like, where the aromatic part may have one or more suitable substituents such as alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. Fluorine, chlorine, bromine, etc.), nitro and the like.
  • alkoxy e.g. methoxy, ethoxy etc.
  • halogen e.g. Fluorine, chlorine, bromine, etc.
  • Alkylene includes straight or branched chain alkylene groups which have up to 9 carbon atoms and by the formula
  • n is an integer from 1 to 9, such as methylene, ethylene, trimethylene, methylethylene, tetramethylene, 1-methyltrimethylene, 2-ethylethylene, pentamethylene, 2-methyltetramethylene, isopropylethylene, hexamethylene, and the like; preferred alkylene radicals have up to 4 carbon atoms and radicals with 3 carbon atoms such as e.g. Trimethylene.
  • the hydrogen atoms can be replaced by other substituents, such as halogen radicals.
  • Alkenylene includes straight or branched chain alkenylene groups with up to 9 carbon atoms, which are represented by the formula
  • n is an integer from 2 to 9, e.g. Vinylene, propenylene (e.g. 1-propenylene, 2-propenylene), 1-methyl propenylene, 2-methyl propenylene, butenylene, 2-ethyl propenylene, pentenylene, hexenylene and the like;
  • the alkenylene radical can particularly preferably have up to 5 carbon atoms and in particular 3 carbon atoms such as e.g. 1-propenylene.
  • the hydrogen atoms can be replaced by other substituents, such as halogen radicals.
  • Haldroxyalkylene can include straight or branched chain alkylene radicals which have up to 9 carbon atoms, at least one selected carbon atom being substituted by a hydroxyl group; these radicals can be represented by the formula
  • hydroxyalkylene groups include hy- droxymethylene, hydroxy ethylene (e.g. 1-hydroxyethylene and 2-hydroxyethylene), hydroxytrimethylene (e.g. 1-hydroxytrimethylene, 2-hydroxytrimethylene and 3-hydroxytrimethylene), hydroxytetramethylene (e.g. 2-hydroxytetramethylene), 2-hydroxy-2-methyltrimethylene , Hydroxypentamethylene (eg 2-hydroxy-pentamethylene), Hydroxyhexamethylene (eg 2-Hydroxyhexa-methylene) and the like.
  • a lower hydroxyalkylene with up to 4 carbon atoms and in particular one with 3 carbon atoms such as 2-hydroxytrimethylene is particularly preferred.
  • the hydrogen atoms can be replaced by other substituents, such as halogen radicals.
  • the radicals can preferably be chosen such that esters are formed on the phosphino group.
  • suitable examples of such esters according to formulas (I) and (II) include alkyl esters (e.g. methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, hexyl ester, etc.);
  • Aralkyl esters (benziesters, phenethyl esters, benzhydryl esters, trityl esters, etc.);
  • Aryl esters e.g. phenyl esters, tolyl esters, naphthyl esters, etc.
  • Aroyl alkyl esters e.g. phenacyl esters etc.
  • silyl esters e.g. from trialkylhalosilyl, dialkyldihalosilyl, alkyltrihalosilyl, dialkylarylhalosilyl, trialkoxyhalosilyl, dialkylaralkylhalosilyl, dialkoxydihalosilyl, trialkoxyhalosilyl, etc.
  • the alkane and / or arene portion can optionally have at least one suitable substituent such as halogen, alkoxy, hydroxy, nitro or the like.
  • the salt compounds of the organophosphorus compounds with organic or inorganic bases e.g. sodium salt, potassium salt, calcium salt, aluminum salt, ammonium salt, magnesium salt, triethylamine salt, ethanolamine salt, dicyclohexylamine salt, ethylenediamine salt, N, N'-dibenzylethylenediamine salt etc.
  • salts with amino acids e.g. arginine salt, aspartic acid salt, glutamic acid salt etc.
  • the compounds of the formulas (I) or (II) used according to the invention can be in their protonated form as the ammonium salt of organic or inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, lactic acid, maleic acid, fumaric acid, oxalic acid , Tartaric acid, benzoic acid, etc. are present.
  • the compounds of the formulas (I) or (IT) used according to the invention allow, for example for double-containing or chiral groups R 1, R 2 , R 3 , Rt, Xi, X 2 or A, the occurrence of spatial isomers.
  • the use of the compounds according to the invention includes all spatial isomers both as pure substances and in the form of their mixtures.
  • organophosphorus compounds are particularly suitable for the therapeutic and prophylactic treatment of infections in humans and animals which are caused by viruses, bacteria, single and multicellular parasites and fungi.
  • the compounds are active against unicellular parasites (protozoa), in particular against pathogens of malaria and sleeping sickness as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidosis, cryptosporidiosis, and sarcolocystosis , Akanthamöbose, Naeglerose, Coccidiosis, Giardiosis and Lambliosis.
  • malaria prophylaxis and as prophylaxis of sleeping sickness and Chagas disease, toxoplasmosis, amoebic dysentery, Leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcolocystosis, acanthamoebosis, cocoonosis, naeglerosis Giardiosis and Lambliosis.
  • the active compounds according to the invention can be used in particular against the following bacteria:
  • Bacteria of the Propionibacteriaceae family in particular the Propionibacterium genus, in particular the Propionibacterium acnes species, Actinomycetaceae bacteria, in particular the Actinomyces genus, Corynebacterium bacteria, in particular the Corynebacterium diphteriae and Corynebacterium pseudote family mycobacteria, bacteria the species Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium, bacteria of the Chlamydiaceae family, in particular the species Chlamydia trachomatis and Chlamydia psittaci, bacteria of the genus Listeria, in particular the species Listeria mon- derhrixysiophysiophythropia , Bacteria of the genus Clostridium, bacteria of the genus Yersinia, of the species Yersinia pestis, Yersinia
  • Organophosphorus compounds and their derivatives are therefore suitable for the treatment of diphtheria, acne vulgaris, listeriosis, erysipelas in animals, gas fires in humans and animals, para-noise burns in humans and animals, tuberculosis in humans and animals, leprosy and other mycobacteriosis in humans and animals, paratuberculosis in animals, plague, mesenteric lymphadenitis and pseudotuberculosis in humans and animals, cholera, legionnaires' disease, Lyme disease in humans and animals, leptospirosis in humans and animals, syphilis, Campylobacter enteritis in humans and animals, Moraxella keratoconjunc -tivitis and serositis of animals, brucellosis of animals and humans, anthrax in humans and animals, actinomycosis in humans and animals, streptotrichoses, psittacosis / ornithosis in animals, Q fever, Ehr
  • a combination with another antibiotic can also be used to treat the above-mentioned diseases.
  • Isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, protionamide and dapsone are particularly suitable for the treatment of tuberculosis for combination preparations with other anti-infectives.
  • the active compounds according to the invention can also be used in particular for infections with the following viruses:
  • Parvoviridae Parvoviruses, Dependovire, Densoviruses, Adenoviridae: Adenoviruses, Mastadeviruses, Aviadenoviruses, Papovaviridae: Papovaviruses, in particular Papillomaviruses (so-called Wartsviruses), Polyomaviruses, in particular JC-Virus, Herpesviruses, and Herpesviruses, and Herpesviruses, and Herpesviruses, and Herpesviruses, and Herpesviruses, and Herpesviruses -Simplex viruses, the varicella / zoster viruses, human cytomegalovirus, Epstein-Barr viruses, all human herpes viruses, human herpes virus 6, human herpes virus 7, human herpes virus 8, Poxviridae: pox viruses, Orthopox, Parapox, Molluscum -Contagiosum virus, avivire,
  • organophosphorus compounds used according to the invention are therefore suitable for combating the following viral infections:
  • the connections described, i.e. the organophosphorus compounds of the formula (I) and (II) and esters and amides thereof on the phosphino group and salts thereof show a strong cytotoxic activity against single and multicellular parasites, in particular against the pathogens of malaria and sleeping sickness.
  • the compounds used in the present invention are useful for the treatment of infectious diseases caused by viruses, bacteria, parasites and fungi in humans and animals.
  • the compounds are also suitable for use in preventing diseases caused by viruses, bacteria, parasites and fungi, in particular as malaria prophylaxis and as sleeping sickness prophylaxis.
  • organophosphorus compounds used according to the invention generally include pharmaceutically acceptable salts, amides, esters, a salt of such an ester, or compounds which, when applied, provide the compounds used according to the invention as metabolites or degradation products, also called "prodrugs", for those Administration can be prepared in any suitable manner analogous to known anti-infectious agents (mixed with a non-toxic pharmaceutically acceptable carrier).
  • Pharmaceutically acceptable salts of the compounds include salts which the compounds of the formulas (I) and (II) used in their protonated form as the ammonium salt of inorganic or organic acids, such as hydrochloric acid, sulfuric acid, citric acid, maleic acid, fumaric acid, tartaric acid, p-toluenesulfonic acid , form.
  • the salts which are formed by a suitable selection of L such as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylamine salt, dicyclohexylamine salt and salts of an amino acid such as arginine salt, aspartic acid salt, glutamic acid salt, are also particularly pharmaceutically suitable.
  • the activity of the substances is determined in a test system.
  • This system is based on the measurement of the inhibition of the growth of bacteria, parasites, viruses, fungi or plants in vitro.
  • test methods are used which are known to the person skilled in the art.
  • the inhibition of malaria parasite growth in blood cultures is determined to determine antimalaria activity.
  • the determination of the antibacterial activity is based on measuring the inhibition of bacterial growth on nutrient media and in liquid cultures.
  • the determination of the antiviral activity is based on inhibition of the formation of viral elements in cell cultures.
  • the determination of the fungicidal activity is based on the inhibition of the growth of fungi on nutrient media and in liquid cultures.
  • the antiparasitic, antiviral, fungicidal or antibacterial activity is further evaluated in the corresponding animal models.
  • the screening for herbicidal activity is determined by means of algae systems and measurement of the isoprene emission from plants under standard conditions.
  • the pharmaceutically active agents can be prepared in the form of pharmaceutical preparations in dosage units. This means that the preparation in the form of individual parts, e.g. B. tablets, dragees, capsules, pills, suppositories and ampoules are present, the active ingredient content of which corresponds to a fraction or a multiple of a single dose.
  • the dosage units can e.g. B. 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose.
  • a single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.
  • Non-toxic, inert pharmaceutically suitable carriers are to be understood as solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all kinds.
  • Tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays may be mentioned as preferred pharmaceutical preparations.
  • Tablets, dragees, capsules, pills and granules latex can contain the active ingredient (s) in addition to the usual carriers, such as (a) bulking agents and extenders, e.g. B starches, milk sugar, cane sugar, glucose, mannitol and silica, (b) binders, e.g.
  • cellulose carboxymethyl cellulose, alginates, gelatin, polyvinylpyrrolidone, (c) humectants, e.g. B-Glyce ⁇ n, (d) disintegrant, eg agar-agar, calcium carbonate and sodium carbonate, (e) solution retarder, eg paraffin and (f) absorption accelerator, eg quaternary ammonium compounds, (g) wetting agent, eg cetyl alcohol, glycerol monostearate , (h) adsorbents, e.g. kaolin and bentonite and (i) lubricants, e.g. B. talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i)
  • the tablets, dragees, capsules, pills and granules can be provided with the customary coatings and casings, optionally containing opacifying agents, and can also be composed such that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, possibly with a delay, where as Embedding compounds such as polymer substances and waxes can be used
  • the active ingredient (s) can, if appropriate, also be present in microencapsulated form with one or more of the carrier substances specified above
  • Suppositories can contain the usual water-soluble or water-insoluble carrier substances in addition to the active substance or substances, e.g. B polyethylene glycols, fats, e.g. B cocoa fat and higher esters (e.g. C 14 alcohol with C 16 fatty acid) or mixtures of these substances
  • ointments, pastes, creams and gels can contain the usual carrier substances, e.g. animal and vegetable fats, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances
  • carrier substances e.g. animal and vegetable fats, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances
  • powders and sprays can contain the usual carrier substances, e.g. milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances.
  • Sprays can additionally contain the usual blowing agents, e.g. chlorofluorocarbons
  • Solutions and emulsions can in addition to the active ingredient (s), the usual carriers such as solvents, solubilizers and emulsifiers, e.g. B water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, in particular cottonseedol, peanut oil, corn oil, olive oil, ricinusol and sesamol, glycerol, glyceryl formalin hol, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances th.
  • solvents e.g. B water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, di
  • solutions and emulsions can also be in sterile and blood-isotonic form.
  • suspensions can contain the usual carriers such as liquid diluents, e.g. B. water, ethyl alcohol, propylene glycol, suspending agents, e.g. B. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • liquid diluents e.g. B. water, ethyl alcohol, propylene glycol
  • suspending agents e.g. B. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth or mixtures of these substances.
  • the formulation forms mentioned can also contain colorants, preservatives and odor and taste-improving additives, e.g. B. peppermint oil and eucalyptus oil and sweeteners, e.g. B. saccharin.
  • the active compounds of the formulas (I) and (II) should be in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5% by weight, preferably of about 0.5 to 95% by weight, of the total mixture.
  • the pharmaceutical preparations can also contain further active pharmaceutical ingredients.
  • the compounds can be used with previously described substances with antibacterial, antiviral, antimyctoic and antiparasitic properties. These include in particular compounds that have already been used in therapy or are still being used. Substances are particularly suitable for this purpose, which are listed in the Red List or in Simon / Stille, Antibiotic Therapy in Clinic and Practice, 9th Edition 1998 Schattauer Verlag, or at http: /www.customs.treas.gov/imp -exp / rulings / harmoniz / hrml29.html listed on the Internet.
  • organophosphorus compounds in the pharmaceutical compositions can be used in combination with sulfonamide, sulfadoxine, artemisinin, atovaquone, quinine, chloroquine, hydroxylchloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, nicazolantil, prazoliquilil, praziquantilil Pyrantel, tiabendazole, diethyl carbazine, piperazine, pyrivinum, metrifonate, oxamniquin, bithionol or suramin or more of these substances are present.
  • the pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. B. by mixing the active ingredient (s) with the carrier (s).
  • the preparations mentioned can be used in humans and animals either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously), intracisternally, intravaginally, intraperitoneally, locally (powder, ointment, drops) and for the therapy of infections in cavities, body cavities.
  • Suitable preparations are injection solutions, solutions and suspensions for oral therapy, gels, pour-on formulations, emulsions, ointments or drops.
  • ophthalmic and dermatological formulations silver and other salts, ear drops, eye ointments, powder or solutions can be used.
  • suitable formulations can also be ingested through feed or drinking water.
  • Gels, powders, powders, tablets, prolonged-release tablets, premixes, concentrates, granules, pellets, tablets, boluses, capsules, aerosols, sprays, inhalants can also be used in humans and animals.
  • the compounds used according to the invention can be incorporated into other carrier materials such as plastics, (plastic chains for local therapy), collagen or bone cement.
  • the active ingredient (s) of the formulas (I) and (II) in total amounts of from about 0.05 to about 600, preferably 0.5 to 200 mg / kg body weight per 24 hours, if necessary in the form of several single doses, to achieve the desired results.
  • a single dose contains the active ingredient (s) preferably in amounts of about 1 to about 200, in particular 1 to 60 mg / kg body weight.
  • the compounds according to the invention can be given in the usual concentrations and preparations in animals together with the feed or with feed preparations or with the drinking water.
  • the compounds used according to the invention can be used excellently as bactericides, fungicides and herbicides in plants.

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  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
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  • Plant Pathology (AREA)
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Abstract

La présente invention concerne l'utilisation de composés organophosphorés correspondant à la formule générale (I) pour la production de médicaments pour le traitement thérapeutique et prophylactique d'infections dues aux virus, bactéries, champignons et parasites, chez les humains et chez les animaux, et en tant que fongicide, bactéricide et herbicide pour des végétaux.
EP99969332A 1998-09-22 1999-09-22 Utilisation de composes organophosphores pour la production de medicaments pour le traitement therapeutique et prophylactique d'infections ou en tant que fongicide, bactericide ou herbicide pour vegetaux Withdrawn EP1115388A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19843222A DE19843222A1 (de) 1998-09-22 1998-09-22 Verwendung von phosphororganischen Verbindungen zur therapeutischen und prophylaktischen Behandlung von Infektionen
DE19843222 1998-09-22
PCT/EP1999/007054 WO2000016757A2 (fr) 1998-09-22 1999-09-22 Utilisation de composes organophosphores pour la production de medicaments pour le traitement therapeutique et prophylactique d'infections ou en tant que fongicide, bactericide ou herbicide pour vegetaux

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EP1115388A1 true EP1115388A1 (fr) 2001-07-18

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EP99969332A Withdrawn EP1115388A1 (fr) 1998-09-22 1999-09-22 Utilisation de composes organophosphores pour la production de medicaments pour le traitement therapeutique et prophylactique d'infections ou en tant que fongicide, bactericide ou herbicide pour vegetaux

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EP (1) EP1115388A1 (fr)
JP (1) JP2003520760A (fr)
KR (1) KR20010075248A (fr)
CN (1) CN1319006A (fr)
AP (1) AP2001002106A0 (fr)
AU (1) AU5981199A (fr)
BR (1) BR9913990A (fr)
CA (1) CA2344867A1 (fr)
DE (1) DE19843222A1 (fr)
IL (1) IL141887A0 (fr)
NO (1) NO20011430L (fr)
OA (1) OA11655A (fr)
PL (1) PL353313A1 (fr)
SK (1) SK3932001A3 (fr)
WO (1) WO2000016757A2 (fr)
ZA (1) ZA200101912B (fr)

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RU2003104525A (ru) * 2000-07-11 2004-06-27 Байер Акциенгезельшафт (De) Применение штаммов вируса parapox ovis для получения антивирусных и противораковых лекарственных средств
WO2002078714A1 (fr) * 2001-03-30 2002-10-10 Jomaa Pharmaka Gmbh Formulations gastro-resistantes de composes anti-infectieux, bloquant la voie metabolique de la 2-c-methylerythrose-4, ainsi que leurs sels et esters
SG11201701928RA (en) 2014-09-12 2017-04-27 Antibiotx Aps Antibacterial use of halogenated salicylanilides
GB201509326D0 (en) 2015-05-29 2015-07-15 Antibio Tx Aps Novel use
CN105055431B (zh) * 2015-08-11 2018-03-13 西南医科大学附属医院 一种具有抗结核菌的药物及其应用
CN108853106B (zh) * 2017-05-09 2021-02-02 中国食品药品检定研究院 亚胺吩嗪类化合物作为狂犬病病毒抑制剂的用途
US11419834B2 (en) 2019-02-25 2022-08-23 Rhode Island Hospital Methods for treating diseases or infections caused by or associated with H. pylori using a halogenated salicylanilide
CA3172672A1 (fr) * 2020-03-26 2021-09-30 Jei Man Ryu Composition pharmaceutique pour prevenir ou traiter une maladie infectieuse epidemique a virus a arn
CN112043707B (zh) * 2020-09-09 2021-07-30 武汉珈创生物技术股份有限公司 氯法齐明和/或其可药用衍生物在制备抗沙粒病毒药物中的应用

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4216226A (en) * 1977-06-06 1980-08-05 Meiji Seika Kaisha, Ltd. Antiviral agent and treatment of viral infections
US4613355A (en) * 1983-08-02 1986-09-23 Satoshi Omura Antibiotic having herbicidal activity
US4693742A (en) * 1983-12-20 1987-09-15 Rohm And Hass Company Herbicidal hydroxyamino phosphonic acids and derivatives
US4846872A (en) * 1986-08-11 1989-07-11 Fujisawa Pharmaceutical Co., Ltd. Herbicide
EP0352508A1 (fr) * 1988-07-05 1990-01-31 Sumitomo Chemical Company, Limited Composition herbicide
WO1996016629A2 (fr) * 1994-11-18 1996-06-06 Amira Inc Composes phosphinico-creatiniques a activite antivirale
WO1999052515A2 (fr) * 1998-04-14 1999-10-21 Hassan Jomaa Utilisation de liaisons organophosphorees dans le traitement et la prevention d'infections

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4216226A (en) * 1977-06-06 1980-08-05 Meiji Seika Kaisha, Ltd. Antiviral agent and treatment of viral infections
US4613355A (en) * 1983-08-02 1986-09-23 Satoshi Omura Antibiotic having herbicidal activity
US4693742A (en) * 1983-12-20 1987-09-15 Rohm And Hass Company Herbicidal hydroxyamino phosphonic acids and derivatives
US4846872A (en) * 1986-08-11 1989-07-11 Fujisawa Pharmaceutical Co., Ltd. Herbicide
EP0352508A1 (fr) * 1988-07-05 1990-01-31 Sumitomo Chemical Company, Limited Composition herbicide
WO1996016629A2 (fr) * 1994-11-18 1996-06-06 Amira Inc Composes phosphinico-creatiniques a activite antivirale
WO1999052515A2 (fr) * 1998-04-14 1999-10-21 Hassan Jomaa Utilisation de liaisons organophosphorees dans le traitement et la prevention d'infections

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GREENWOOD D: "Fosfomycin and fosmidomycin" ANTIBIOTICS AND CHEMOTHERAPY, Seiten 357-359, *
See also references of WO0016757A2 *

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Publication number Publication date
KR20010075248A (ko) 2001-08-09
DE19843222A1 (de) 2000-03-30
SK3932001A3 (en) 2001-08-06
CN1319006A (zh) 2001-10-24
PL353313A1 (en) 2003-11-17
AU5981199A (en) 2000-04-10
NO20011430D0 (no) 2001-03-21
NO20011430L (no) 2001-05-09
BR9913990A (pt) 2001-10-23
OA11655A (en) 2004-12-08
AP2001002106A0 (en) 2001-03-31
ZA200101912B (en) 2002-03-07
IL141887A0 (en) 2002-03-10
JP2003520760A (ja) 2003-07-08
CA2344867A1 (fr) 2000-03-30
WO2000016757A8 (fr) 2000-06-29
WO2000016757A2 (fr) 2000-03-30

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