[go: up one dir, main page]

WO2001060829A1 - Composes organophosphores et leur utilisation - Google Patents

Composes organophosphores et leur utilisation Download PDF

Info

Publication number
WO2001060829A1
WO2001060829A1 PCT/EP2000/001313 EP0001313W WO0160829A1 WO 2001060829 A1 WO2001060829 A1 WO 2001060829A1 EP 0001313 W EP0001313 W EP 0001313W WO 0160829 A1 WO0160829 A1 WO 0160829A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydroxy
oxo
acid amide
butyric acid
viruses
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.)
Ceased
Application number
PCT/EP2000/001313
Other languages
German (de)
English (en)
Inventor
Hassan Jomaa
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Jomaa Pharmaka GmbH
Original Assignee
Jomaa Pharmaka GmbH
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.)
Filing date
Publication date
Application filed by Jomaa Pharmaka GmbH filed Critical Jomaa Pharmaka GmbH
Priority to AU2000231564A priority Critical patent/AU2000231564A1/en
Priority to EP00909201A priority patent/EP1255762A1/fr
Priority to CA002399947A priority patent/CA2399947A1/fr
Priority to PCT/EP2000/001313 priority patent/WO2001060829A1/fr
Priority to JP2001560213A priority patent/JP2004508283A/ja
Publication of WO2001060829A1 publication Critical patent/WO2001060829A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • 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
    • 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
    • A01N57/22—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing aromatic radicals
    • 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
    • A01N57/24—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing heterocyclic 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
    • A01P13/02—Herbicides; Algicides selective
    • 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
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/302—Acyclic unsaturated acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/306—Arylalkanephosphinic acids, e.g. Ar-(CH2)n-P(=X)(R)(XH), (X = O,S, Se; n>=1)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5304—Acyclic saturated phosphine oxides or thioxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/50—Organo-phosphines
    • C07F9/53—Organo-phosphine oxides; Organo-phosphine thioxides
    • C07F9/5333—Arylalkane phosphine oxides or thioxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/58—Pyridine rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
    • 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

  • the invention relates to organophosphorus compounds and their salts. Esters and amides and their use in the therapeutic and prophylactic treatment of infections in humans and animals caused by viruses, bacteria, fungi and parasites and their use as fungicides, bactericides and herbicides in plants.
  • the organophosphorus compounds comprise phosphinoyl derivatives. Phosphinic acid derivatives and phosphonic acid derivatives.
  • the object of the present invention is therefore to provide a substance that is universal in infections by viruses, bacteria.
  • Fungi and parasites can be used in humans and animals and as a fungicide, bactericide and herbicide in plants and 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. Bacteria. Fungi, single and multicellular parasites as well as a fungicidal, bactericidal and herbicidal effect on plants.
  • organophosphorus compounds according to the invention correspond to the general formula (I):
  • A is propylene, 2-oxopropylene or 3-oxopropylene
  • R- is selected from the group.
  • Xi are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted Hydroxvalkvl, 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 and in which R 2 and R 3 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl.
  • substituted and unsubstituted hydroxvalkvl 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.
  • OX 2 or OX 3 exists. wherein X or X may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxylalkyl.
  • R is preferably selected from the group consisting of a hydrogen radical, a methyl radical, an ethyl radical and a phenyl radical.
  • R 2 and R 3 are preferably identical or different and selected from the group consisting of a methyl radical, an ethyl radical, OX 2 and OX 3 , X and X 3 being particularly preferably selected from the group consisting of sodium, a Methyl group, an ethyl group and a phenyl group.
  • 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 Weil include aliphatic, aromatic and / or heterocyclic 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, isopropoxycarbonyl, 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, may optionally have one or more suitable substituents, such as amino, halogen (e.g. fluorine, chlorine, bromine etc.), hydroxy, hydroxyimino.
  • suitable substituents such as amino, halogen (e.g. fluorine, chlorine, bromine etc.), hydroxy, hydroxyimino.
  • Acylamino e.g. benzyloxycarbonylamino etc.
  • acyloxy e.g. acetoxy, benzoyloxy etc.
  • preferred aliphatic acyl radicals with such substituents e.g. with amino. Carboxy, amino and carboxy, halogen.
  • Aromatic acyl radicals are those acyl radicals which originate 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 already started
  • 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 at least 25 has a 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 26 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 26 carbons, which has at least one hydroxyl group, preferably one or two hydroxyl groups.
  • Alkenyl includes straight or branched chain alkenyl groups with up to 26 carbon atoms. Substance atoms, such as vinyl. Propenyl (e.g. 1-propenyl, 2-propenyl), 1-methyl propenyl, 2-methyl propenyl, butenyl. 2-Ethylpropenyl. Pentenyl, hexenyl.
  • Alkynyl includes straight or branched chain alkynyl groups with up to 26 carbon atoms.
  • Cycloalkyl preferably represents an optionally substituted C 3-7 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. Tritvl 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.
  • esters can also be chosen so that esters are formed on the phosphono group or phosphino group.
  • Suitable examples of such esters according to the formula (I) include generally suitable mono- and diesters, for example alkyl esters (for example methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, hexyl ester, etc.); Aralkyl esters (benzyl esters, phenethyl esters, benzhydryl esters, trityl esters, etc.); Aryl esters (for example phenyl esters, tolyl esters, naphthyl esters, etc.); Aroyl alkyl esters (eg phenacyl esters etc.); and silyl esters (e.g.
  • dialkyldihalosilyl from trialkylhalosilyl, dialkyldihalosilyl, alkyltrihalosilyl. dialkylarylhalosilyl, trialkoxyhalosilyl, dialkylaralkylhalosilyl, dialkoxydihalosilyl, trialkoxyhalosilyl, etc.) and the like.
  • the alkane and / or arene portion can optionally have at least one suitable substituent such as halogen, alkoxy, hydroxy, nitro or the like.
  • methyl, ethyl and phenyl esters are particularly preferred.
  • X 2 and X 3 can be a metal of the first, second or third main group of the periodic table, ammonium, substituted ammonium, or ammonium compounds derived from ethylenediamine or amino acids. That is, the salt compounds of the organophosphorus compounds with organic or inorganic bases (for example sodium salt, potassium salt, calcium salt, aluminum salt, ammonium salt, magnesium salt, trie thylamine salt, ethanolamine salt. Dicyclohexylamine. Ethylenediamine salt, N, N'-dibenzylethylenediamine salt etc.) and salts with amino acids (for example arginine acid, aspartic acid salt, glutamic acid salt etc.) and the like are formed. The sodium salt is preferred.
  • organic or inorganic bases for example sodium salt, potassium salt, calcium salt, aluminum salt, ammonium salt, magnesium salt, trie thylamine salt, ethanolamine salt. Dicyclohexylamine. Ethylenediamine salt, N, N'-
  • the compounds according to the formula (I) according to the invention can, however, in their protonated form as ammonium salt of organic or inorganic acids, such as hydrochloric acid. Hydrobromic. Sulfuric acid. Nitric acid. Methane sulfonic acid. p-toluenesulfonic acid. Acetic acid. Lactic acid. Maleic acid. Fumaric acid. Oxalic acid. Tartaric acid. Benzoic acid. etc. are available.
  • organic or inorganic acids such as hydrochloric acid. Hydrobromic. Sulfuric acid. Nitric acid. Methane sulfonic acid. p-toluenesulfonic acid. Acetic acid. Lactic acid. Maleic acid. Fumaric acid. Oxalic acid. Tartaric acid. Benzoic acid. etc. are available.
  • the compounds of formula (I) according to the invention allow spatial isomers to occur for double or chiral groups R 1, R 2 , R 3 , Xi, X2, 3 or A.
  • the use of the compounds according to the invention includes all spatial isomers both as pure substances and in the form of their mixtures.
  • N-hydroxy-4-phosphonobutyric acid amide monosodium salt and N-hydroxy-N-yl-4-phosphonobutyric acid amide monosodium salt are particularly preferred.
  • the organophosphorus compounds are particularly suitable for the therapeutic and prophylactic treatment of infections in humans and animals caused by viruses. Bacteria, single and multicellular parasites and fungi are caused. According to the invention, unicellular parasites are only to be understood as protozoa in accordance with the narrow definition of parasitology.
  • the compounds are active against unicellular parasites (protozoa), in particular against pathogens of malaria and sleeping sickness as well as Chagas disease, toxoplasmosis. the amoebic dysentery, the leishmaniasis. trichomoniasis. pneumocystosis. the Balantiosis. cryptosporidiosis. Sarcocystosis. the Akanthamöbose. the nail rose. coccidiosis. Giardiosis and Lambliosis.
  • toxoplasmosis amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis. balantidiosis, cryptosporidiosis, sarcocystosis. the Akanthamöbose. the nail rose. coccidiosis. Giardiosis and Lambliosis.
  • the active compounds according to the invention can be used in particular against the following bacteria:
  • Bacteria of the Propionibacteriaceae family especially the genus Propionibacterium, especially the species Propionibacterium acnes; Bacteria of the Actinomycetaceae family, in particular of the Actinomyces genus; Bacteria of the genus Corynebacterium, in particular the species Corynebacterium diphteriae and Corynebacterium pseudotuberculosis; Bacteria of the family Mycobacteriaceae, of the genus Mycobacterium, in particular the species Mycobacterium leprae, Mycobacterium tuberculosis.
  • the genera Mycoplasma and Ureaplasma especially the species Mycoplasma pneumoniae; Bacteria of the genus Brucella; Bacteria of the genus Bordetella; Bacteria of the family Neiseriaceae. especially the genera Neisseria and Moraxella. especially the species Neiseria meningitides. Neisseria gonorrhoeae and Moraxella bovis; Bacteria of the Vibrionaceae family. especially the genera Vibrio, Aeromonas. Plesiomonas and Photobacterium. especially the Vibrio cholerae species. Vibrio anguillarum and Aeromonas salmonici- das: bacteria of the genus Campylobacter, especially the species Campylobacter jejuni.
  • Campylobacter coli and Campylobacter fetus Bacteria of the genus Helicobacter, in particular the species Helicobacter pylori: bacteria of the Spirochaetaceae and Leptospiraceae families, in particular of the Treponema genus. Borrelia and Leptospira, especially Borrelia burgdorferi; Bacteria of the genus Actinobacillus; Bacteria of the Legionellaceae family.
  • Bacteria of the Rickettsiaceae family and Bartonellaceae family bacteria of the genera Nocardia and Rhodococcus; Bacteria of the genus Dermatophilus bacteria of the family Pseudomonadaceae, in particular of the genera Pseudomonas and Xanthomonas; Bacteria of the Enterobacteriaceae family, especially of the Escherichia genera. Klebsieila, Proteus. Providencia, Salmonella.
  • Serratia and Shigella Bacteria of the Pasteurellaceae family, especially of the genus Haemophilus; Bacteria of the Micrococcaeeae family, in particular the genera Micrococcus and Staphylococcus; Bacteria of the Streptococcaceae family. especially the genera Streptococcus and Enterococcus and bacteria of the family Bacillaceae, especially the genera Bacillus and Clostridium.
  • Organophosphorus compounds and their derivatives are therefore suitable for the treatment of diphtheria.
  • Syphilis Campylobacter enteritis in humans and animals, Moraxella keratoconjunctivitis and serositis in animals, brucellosis in animals and humans, anthrax in humans and animals, actinomycosis in humans and animals, streptotrichoses, psittacosis / ornithosis in animals, Q fever, Ehrlichiosis ,
  • a combination with another antibiotic can also be used to treat the above-mentioned diseases.
  • Isoniazid, rifampicin are particularly suitable for combination preparations with other anti-infectives.
  • Streptomycin, protionamide and dapsone for the treatment of tuberculosis.
  • the active compounds according to the invention can also be used in particular for infections with the following viruses: Parvoviridae: Parvoviruses, Dependoviruses. Denso viruses; Adenoviridae: adenoviruses. Mastadeviruses, aviadenoviruses: Papovaviridae: Papovaviruses, in particular papillomaviruses (so-called wart viruses), polyomaviruses. especially JC virus. BK virus, and miopapovavirus; Herpesviridae: All herpes viruses, especially herpes simplex viruses. of the varicella / zoster viruses. human cytomegalovirus, Epstein-Barr virus, all human herpes viruses.
  • HTL viruses human T-cell leukemia virus, oncornaviruses.
  • Leukemia viruses all HTL viruses, human T-cell leukemia virus, oncornaviruses.
  • organophosphorus compounds according to the invention are therefore suitable for combating the following viral infections:
  • Eradication of papillomaviruses for the prevention of tumors in particular of tumors of the genital organs caused by papillomaviruses in humans, eradication of JC viruses and BK viruses, eradication of herpes viruses, eradication of human herpes viruses 8 for the treatment of Kaposi's sarcoma, eradication of cytomegaloviruses Transplants, eradication of Eppstein-Barr viruses before transplantation and for the prevention of Eppstein-Barr virus-associated tumors, eradication of hepatitis viruses for treatment of chronic liver diseases and for the prevention of liver tumors and cirrhosis.
  • the nervous system poliomyelitis, meningoencephalitis, encephalitis, subacute sclerosing panencephalitis, SSPE, progressive multifocal leukoencephalopathy, lymphocytic choriomeningitis (
  • the connections described, i.e. the organophosphorus compounds of the formula (I), and esters and amides thereof on the phosphono- or phosphino group and salts thereof show a strong cytotoxic activity against single- and multicellular parasites. especially against the pathogens of malaria and sleeping sickness.
  • the compounds of the invention are useful for the treatment of infectious diseases caused by viruses. Bacteria, parasites and fungi are caused 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.
  • the organophosphorus compounds 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 according to the invention as metabolites or degradation products, also called “prodrugs”, can be administered for administration in any suitable manner analogously 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 formula according to the invention 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 suitable selection of X 2 and X, such as sodium salt, are also particularly pharmaceutically suitable.
  • Dicyclohexylamine salt and salts of an amino acid such as arginine salt, aspartic acid salt, glutamic acid salt.
  • 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 available, 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 and coated tablets are the preferred pharmaceutical preparations. Capsules, pills, granules. Suppositories, solutions. Suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays called. Tablets, coated tablets, capsules, pills and granules can contain the active ingredient (s) in addition to the usual carriers, such as (a) fillers and extenders, e.g. B. starches, milk sugar, cane sugar, glucose, mannitol and silica, (b) binders, e.g. B.
  • fillers and extenders e.g. B. starches, milk sugar, cane sugar, glucose, mannitol and silica
  • binders e.g. B.
  • humectants e.g. B. glycerin
  • disintegrant e.g. B. agar-agar, calcium
  • the tablets, dragees, capsules, pills and granules can be provided with the usual coatings and casings, optionally containing opacifying agents, and can also be composed such that they contain the active ingredient (s) only or preferably in a particular one Part of the intestinal tract may be released with a delay, with z.
  • B. 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 excipients specified above.
  • Suppositories can contain the usual water-soluble or water-insoluble excipients in addition to the active ingredient (s), e.g. B. polyethylene glycols, fats, e.g. B. cocoa fat and higher esters (z. B. C 14 alcohol with C16 fatty acid) or mixtures of these substances.
  • active ingredient e.g. B. polyethylene glycols
  • fats e.g. B. cocoa fat and higher esters (z. B. C 14 alcohol with C16 fatty acid) or mixtures of these substances.
  • Pastes, creams and gels can contain the usual excipients in addition to the active ingredient (s), e.g. B. animal and vegetable fats, waxes, paraffins, starch. Astragalus. Cellulose derivatives. Polyethylene glycols. Silicones, bentonites. Silicic acid, talc and zinc oxide or mixtures of these substances.
  • active ingredient e.g. B. animal and vegetable fats, waxes, paraffins, starch. Astragalus. Cellulose derivatives. Polyethylene glycols. Silicones, bentonites. Silicic acid, talc and zinc oxide or mixtures of these substances.
  • Powder and sprays can contain the usual excipients in addition to the active ingredient (s), e.g. B. milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances.
  • Sprays can also use the usual blowing agents, e.g. B. chlorofluorocarbons.
  • solutions and emulsions can contain 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. especially cottonseed oil. Peanut oil, corn oil. Olive oil, castor oil and sesame oil. Glycerin, glycerin formal, tetrahydrofurfuryl alcohol. Contain polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.
  • solvents e.g. B. water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate.
  • Benzyl alcohol benzyl benzoate.
  • Propylene glycol 1.3-butylene glyco
  • 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. Containing aluminum metahydroxide, bentonite, agar-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. Containing aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.
  • the formulation forms mentioned can also be colorants.
  • Preservatives as well as odor and taste-improved additives e.g. B. peppermint oil and eucalyptus oil and Sweeteners, e.g. B. saccharin.
  • the active compounds of the formula (I) should be present in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5% by weight. preferably from about 0.5 to 95% by weight of the total mixture.
  • the pharmaceutical preparations can also contain further active pharmaceutical ingredients.
  • organophosphorus compounds in the pharmaceutical compositions in combination with sulfonamide, sulfadoxine Artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine. Pyrimethamine, armesin. Tetracycline. Doxycycline, proguanil. Metronidazole, praziquantil. Niclosamide. Mebendazole, pyrantel. Tiabendazole, diethyl carbazine. Piperazine. Pyrivinum. Metrifonate. Oxamniquine. 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 either be oral, rectal, parenteral (intravenous, intramuscular, subcutaneous), intracisternal. intravaginal, intraperitoneal, local (powder, ointment, drops) and for the treatment of infections in cavities.
  • Body cavities can be applied.
  • Injection solutions come as suitable preparations. Solutions and suspensions for oral therapy, gels. Pour-on formulations. Emulsions. Ointments or drops in question.
  • ophthalmic and dermatological formulations can be used. 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 can also be used. Granules, pellets, tablets. Boli, capsules, aerosols,
  • Sprays, inhalants can be used in humans and animals.
  • the compounds 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 formula (I) in a total amount of from about 0.05 to about 600. preferably 0.5 to 200 mg kg of 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, especially 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 of the invention can be outstanding as bactericides. Fungicides and herbicides are used in plants.
  • the compounds according to the invention are notable for good herbicidal activity.
  • the invention accordingly also relates to a method for controlling unwanted plant life in crops of crops, the area in which they are cultivated being treated with an effective amount of a compound of the formula (I) according to the invention or of an agent comprising such a derivative.
  • 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. Mushrooms 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.
  • Substances that show efficacy in the in vitro measurement systems are further investigated in in vivo models.
  • 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.
  • N-Hydroxy-4- (diethylphosphono) butyric acid amide (1 a 2.52 g (10 mmol) of 4-phosphonobutyric acid triethyl ester are dissolved in 20 ml of anhydrous methanol.
  • a solution of 11 mmol of hydroxylamine in anhydrous methanol (filtered from 765 mg (11 mmol) Hydroxylamine hydrochloride and 253 mg (11 mmol) sodium in methanol) are added dropwise at 0 ° C.
  • the resulting mixture is mixed with 10 mmol sodium methanolate (from 230 mg (10 mmol) sodium) in anhydrous mathanol at 0 ° C.
  • Example 2a N-Hydroxy-N-methyl-4- (diethylphosphono-butyric acid amide (2a)
  • the procedure is similar, using N-methylhydroxylamine instead of hydroxylamine, and N-hydroxy-N-methyl-4- (diethylphosphono) butyric acid amide ( 2a) obtained as colorless crystals and in moderate yield.
  • Example 3 The procedure corresponding to Example 3 is based on N-hydroxy-N-methyl-4- (diethylphosphono) butyric acid amide (2a) and N-hydroxy-N-methyl-4-phosphonobutyric acid amide (2b) in the form of colorless crystals and in medium yield receive.
  • N-hydroxy-N-methyl-4-phosphonoacetoacetic acid amide (4b) is obtained in the form of colorless crystals and in medium yield.
  • Substance 1 N-hydroxy-4-phosphonobutyric acid amide sodium salt
  • Substance 2 N-Hydroxy-N-methyl-4-phosphonobutyric acid amide monosodium salt
  • Substance 3 N-hydroxy-N-phenyl 4-phosphono-butyric acid amide monosodium salt substance 4: N-hydroxy-4- (P-memyl-phosphinato) -butyric acid amide monosodium salt substance 5: N-hydroxy-N-methyl-3-oxo-4- (P-methyl-phosphinato ) -butyric acid amide monosodium salt substance 6: N-hydroxy-3-oxo-4- (P-methyl l-phosphinato) -butyric acid amide monosodium salt substance 7: N-hydroxy-N-methyl-3-oxo-4-phosphono-butyric acid amide -monosodium salt substance 8: N-hydroxy-3-oxo-4-phosphono-butyric acid amide
  • DOXP reductoisomerase from Escherichia coli and Helicobacter pylori The DOXP reductoisomerase from Escherichia coli was expressed as a recombinant protein in E. coli.
  • a dilution series with the concentrations 32, 16, 8, 4, 2, 1 and 0 mg 1 " 'of the individual compounds 1 to 8 and 11 and 12 was placed in 5 culture tubes in LB medium in a volume of 0.5 ml.
  • the tubes were inoculated with 10 ⁇ l each from the overnight culture of E. coli Kl 2 and shaken overnight at 37 ° C.
  • the growth of the bacteria was assessed by turbidity of the medium, the results are shown in Table II.
  • Plasmodium falciparum pathogen of malaria tropica
  • the antimalarial activity of substances 1 to 12 was determined on in vitro cultures of the malaria pathogen Plasmodium falciparum.
  • the wells of a 96-well microtiter plate were each with 200 ⁇ l
  • An asynchronous Plasmodium falciparum culture was loaded at 0.4% parasitemia and 2% hematocrit.
  • a serial dilution series of the compounds was then prepared in three steps between concentrations of 100 ⁇ mol l "1 and 0.14 nmol l " 1.
  • the plates were prepared incubated at 37 ° C., 3% CO 2 and 5% 0 2 over a period of 48 hours.
  • the inhibition of the growth of the plants examined is given in percent in the tables.
  • the damage patterns mean:
  • the damage pattern in monocotyledonous plants is not quite as noticeable as in dicotyledonous plants.
  • the brightenings are usually only at the tips of the shoots.
  • I general white coloring of the leaves.
  • HYDRO pre-emergence test substance 4000 / ha
  • the herbicidal activity is as in Example 12, but with N-4-phosphono-N-hydroxy
  • N-methylbutyric acid amide sodium salt investigated as an active ingredient. The results are shown in Tables VII to IX.
  • test substance 4000 g / ha
  • Test substance expenditure 2000 g / ha

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Environmental Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

L'invention concerne des composés organophosphorés de formule générale (I), dans laquelle A représente propylène, 2-oxopropylène ou 3-oxopropylène. L'invention concerne également leur utilisation pour le traitement thérapeutique et prophylactique, chez l'homme et les animaux, d'infections dues à des virus, bactéries, champignons et parasites, ainsi que leur utilisation comme fongicide, bactéricide et herbicide pour des végétaux.
PCT/EP2000/001313 2000-02-18 2000-02-18 Composes organophosphores et leur utilisation Ceased WO2001060829A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU2000231564A AU2000231564A1 (en) 2000-02-18 2000-02-18 Phosphororganic compounds and the use thereof
EP00909201A EP1255762A1 (fr) 2000-02-18 2000-02-18 Composes organophosphores et leur utilisation
CA002399947A CA2399947A1 (fr) 2000-02-18 2000-02-18 Composes organophosphores et leur utilisation
PCT/EP2000/001313 WO2001060829A1 (fr) 2000-02-18 2000-02-18 Composes organophosphores et leur utilisation
JP2001560213A JP2004508283A (ja) 2000-02-18 2000-02-18 有機リン化合物およびその使用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2000/001313 WO2001060829A1 (fr) 2000-02-18 2000-02-18 Composes organophosphores et leur utilisation

Publications (1)

Publication Number Publication Date
WO2001060829A1 true WO2001060829A1 (fr) 2001-08-23

Family

ID=8163836

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/001313 Ceased WO2001060829A1 (fr) 2000-02-18 2000-02-18 Composes organophosphores et leur utilisation

Country Status (5)

Country Link
EP (1) EP1255762A1 (fr)
JP (1) JP2004508283A (fr)
AU (1) AU2000231564A1 (fr)
CA (1) CA2399947A1 (fr)
WO (1) WO2001060829A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO2005016942A1 (fr) * 2003-08-14 2005-02-24 Bioagency Ag Derives phosphoro-organiques de 4-iminohydantoine
EP1686982A4 (fr) * 2003-11-19 2007-03-21 Vecta Ltd Procedes et compositions destines au traitement de maladies associees a l' helicobacter pylori au moyen de composes contenant un pont endoperoxyde
AU2007100477B4 (en) * 2007-06-05 2007-07-05 Jurox Pty Ltd Parasiticide Composition
US10463680B2 (en) 2015-05-29 2019-11-05 UNION therapeutics A/S Halogenated salicylanilides for treating clostridium infections
US10758553B2 (en) 2014-09-12 2020-09-01 UNION therapeutics A/S Antibacterial use of halogenated salicylanilides
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

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115502207B (zh) * 2022-08-15 2025-04-18 南华大学 羟肟酸基-膦酸酯/次膦酸化合物及其制备方法与应用

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2733658A1 (de) * 1976-07-27 1978-02-09 Fujisawa Pharmaceutical Co Hydroxylaminohydrocarbylphosphonsaeurederivate, verfahren zur herstellung derselben und diese enthaltende pharmazeutische mittel
JPS61106504A (ja) * 1984-10-30 1986-05-24 Teijin Ltd 除草剤
WO1999052515A2 (fr) * 1998-04-14 1999-10-21 Hassan Jomaa Utilisation de liaisons organophosphorees dans le traitement et la prevention d'infections
WO2000004031A1 (fr) * 1998-07-15 2000-01-27 Hassan Jomaa Composes organiques de phosphore et leur utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2733658A1 (de) * 1976-07-27 1978-02-09 Fujisawa Pharmaceutical Co Hydroxylaminohydrocarbylphosphonsaeurederivate, verfahren zur herstellung derselben und diese enthaltende pharmazeutische mittel
JPS61106504A (ja) * 1984-10-30 1986-05-24 Teijin Ltd 除草剤
WO1999052515A2 (fr) * 1998-04-14 1999-10-21 Hassan Jomaa Utilisation de liaisons organophosphorees dans le traitement et la prevention d'infections
WO2000004031A1 (fr) * 1998-07-15 2000-01-27 Hassan Jomaa Composes organiques de phosphore et leur utilisation

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 093, no. 19, 10 November 1980, Columbus, Ohio, US; abstract no. 186456, KAMIYA T ET AL: "Studies on new phosphonic acid-containing antibiotics: synthesis of FR-31564 and related antibiotics" XP002122512 *
CHEMICAL ABSTRACTS, vol. 105, no. 19, 10 November 1986, Columbus, Ohio, US; abstract no. 166897, YAMAJI T ET AL: "N-Substituted alkyl amine phosphates as herbicides" XP002122513 *
CURR. CHEMOTHER. INFECT. DIS., PROC. INT. CONGR. CHEMOTHER., 11TH (43MKAT);1980; VOL.1,; PP.355-8, Fujisawa Pharm. Co., Ltd.;Res. Lab.; Osaka; Japan *
VERLINDE C L M J ET AL: "Structure of the complex between trypanosomal triosephosphate isomerase and N-hydroxy-4-phosphono-butanamide: Binding at the active site despite an "open" flexible loop conformation", PROTEIN SCI. (PRCIEI,09618368);1992; VOL.1 (12); PP.1578-84, Univ. Groningen;Bioson Res. Inst.; Neth. (NL), XP000952324 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
WO2005016942A1 (fr) * 2003-08-14 2005-02-24 Bioagency Ag Derives phosphoro-organiques de 4-iminohydantoine
EP1686982A4 (fr) * 2003-11-19 2007-03-21 Vecta Ltd Procedes et compositions destines au traitement de maladies associees a l' helicobacter pylori au moyen de composes contenant un pont endoperoxyde
AU2007100477B4 (en) * 2007-06-05 2007-07-05 Jurox Pty Ltd Parasiticide Composition
US10758553B2 (en) 2014-09-12 2020-09-01 UNION therapeutics A/S Antibacterial use of halogenated salicylanilides
US10463680B2 (en) 2015-05-29 2019-11-05 UNION therapeutics A/S Halogenated salicylanilides for treating clostridium infections
US10857164B2 (en) 2015-05-29 2020-12-08 UNION therapeutics A/S Halogenated salicylanilides for treating Clostridium infections
US11529361B2 (en) 2015-05-29 2022-12-20 UNION therapeutics A/S Halogenated salicylanilides for treating Clostridium infections
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

Also Published As

Publication number Publication date
AU2000231564A1 (en) 2001-08-27
CA2399947A1 (fr) 2001-08-23
EP1255762A1 (fr) 2002-11-13
JP2004508283A (ja) 2004-03-18

Similar Documents

Publication Publication Date Title
EP1071409B1 (fr) Utilisation de liaisons organophosphorees dans le traitement et la prevention d'infections
EP1095050A1 (fr) Composes organiques de phosphore et leur utilisation
WO2000066094A2 (fr) Utilisation de composes comportant un heterocycle azote-oxygene
EP1140952B1 (fr) Composes organophosphoriques et leur utilisation
EP1133500B1 (fr) Composes phosphororganiques et leur utilisation
DE19903398A1 (de) Verwendung von Thiadiazolderivaten zur prophylaktischen und therapeutischen Behandlung von Infektionen
EP1255762A1 (fr) Composes organophosphores et leur utilisation
DE19843383A1 (de) Phosphororganische Verbindungen und ihre Verwendung
EP1115388A1 (fr) 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
WO2000044358A2 (fr) Utilisation de composes organophosphores pour la prophylaxie et le traitement des infections
WO2000017212A1 (fr) Composes organophosphores et leur utilisation
EP1272198A1 (fr) Utilisation de composes organophosphores pour la fabrication d'un medicament destine au traitement d'infections
WO2001093872A1 (fr) Utilisation de derives d'acide hydroxamique organophosphores pour la fabrication de medicaments
DE19859668A1 (de) Verwendung von Bisphosphonaten zur Prophylaxe und zur Behandlung von infektiösen Prozessen
DE19843360A1 (de) Phosphororganische Verbindungen und ihre Verwendung
DE19843334A1 (de) Schwefelorganische Verbindungen und ihre Verwendung
DE19831639C1 (de) Phosphororganische Verbindungen und ihre Verwendung
WO2000003699A2 (fr) Medicaments contenant des derives d'acide phosphonique comme principe actif et leur utilisation
DE19903666A1 (de) Arzneimittel mit einem Gehalt an 3-Isoxazolidinonen und Hydroxylaminsäuren als Wirkstoff und ihre Verwendung
DE10356410A1 (de) Phosphororganische Verbindungen und deren Verwendung
WO1999066875A2 (fr) Preparation combinee de composes a action anti-infectieuse inhibant la voie metabolique de la 2-c-methylerythrose-4, et inhibiteurs du metabolisme lipidique
DE10337761A1 (de) Phosphororganische 4-Iminohydantoinderivate

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2399947

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 10204068

Country of ref document: US

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2001 560213

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 2000909201

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2000909201

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 2000909201

Country of ref document: EP