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WO2001093872A1 - Utilisation de derives d'acide hydroxamique organophosphores pour la fabrication de medicaments - Google Patents

Utilisation de derives d'acide hydroxamique organophosphores pour la fabrication de medicaments Download PDF

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WO2001093872A1
WO2001093872A1 PCT/EP2001/006539 EP0106539W WO0193872A1 WO 2001093872 A1 WO2001093872 A1 WO 2001093872A1 EP 0106539 W EP0106539 W EP 0106539W WO 0193872 A1 WO0193872 A1 WO 0193872A1
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substituted
viruses
genus
unsubstituted
bacteria
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English (en)
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Hassan Jomaa
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Jomaa Pharmaka GmbH
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Jomaa Pharmaka GmbH
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    • 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
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • 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
    • C07F9/38—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
    • C07F9/547—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
    • C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07F9/6533—Six-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
    • C07F9/655—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
    • 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 the use of organophosphorus hydroxamic acid derivatives and their salts, esters and amides for the therapeutic and prophylactic treatment of infections.
  • the object of the present invention is therefore to provide a substance which can be used universally in infections by viruses, bacteria, fungi and parasites in humans and animals and which fulfills the conditions specified above.
  • Phosphonomethylglycylhydroxamic acid and its salts have already been described as herbicides in European Patent Publication No. 0 039 310.
  • A is selected from the group consisting of -CR 5 Pv6-, -CR 5 R ⁇ ; CH (OH) -, - CRsReCO- and - COCR5R5-, in which Ri is selected from the group consisting of hydrogen , substituted and unsubstituted alkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted alkylcycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted and unsubstituted heterocyclic radical, substituted and unsubstituted alkyl heterocyclic radical, a metal of the first, second or third main group of the periodic table, ammonium, substituted ammonium and ammonium compounds which
  • R t is preferably a hydrogen, a metal of the first, second or third main group of the periodic table, such as Na, K, Ca, Mg, Al, Cu and ammonium, substituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids.
  • Rg and R are preferably selected independently from the group consisting of hydrogen, methyl, ethyl, OXg and OX, OXg and OX 9 preferably being selected from the group consisting of the first, second or third main group of the periodic table, such as Na , K, Ca, Mg, Al, Cu and ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids.
  • 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, triethylamine salt, ethanolamine salt, dicyclohexylamine salt, ethylene diamine salt, N, N'-dibenzylethylenediamine salt etc.
  • salts with amino acids eg arginine salt, aspartic acid salt, glutamic acid salt etc.
  • 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.
  • acyl groups are given below.
  • -— 'As aliphatic acyl groups are derived from an aliphatic acid
  • 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, can optionally have one or more suitable substituents, such as amino, halogen (for example fluorine, chlorine, bromine, etc.), hydroxy, hydroxyl ino , 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, hydroxyl ino , Carboxy, alkoxy (e.g. methoxy
  • 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 have already been specified.
  • arylanoyl substituted with halogen and hydroxy or with halogen and acyloxy and aralkanoyl substituted with hydroxy, hydroxyimino, dihalogenalkanoyloxyimino are also given
  • 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, pyrrolocarbonyl, 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 thiophene-ylacetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino-4- thiazolyl) -2-methoxyiminoacetyl etc.) and the like.
  • nitrogen, oxygen and sulfur for example thiophene-ylacetyl, 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 18 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like.
  • Alkenyl includes straight-chain or branched-chain alkenyl groups with up to 18 carbon atoms, such as vinyl, propenyl (eg 1-propenyl, 2-propenyl), 1- Methyl propenyl, 2-methyl propenyl, butenyl, 2-ethyl propenyl, pentenyl, hexenyl.
  • Alkynyl includes straight or branched chain alkynyl groups with up to 18 carbon atoms.
  • Cycloalkyl stands for an optionally substituted C3-C-cycloalkyl or a bi- or tricycloalkyl from C 3 -C 7 rings; Possible substituents include alkyl, alkenyl, alkynyl, alkoxy (eg methoxy, ethoxy etc.), halogen (eg fluorine, chlorine, bromine etc.), nitro and the like.
  • a heterocyclic radical is accordingly a cycloalkyl as defined above in which one, two or more carbon atoms in the ring are independently replaced by oxygen, nitrogen or sulfur atoms.
  • 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 can optionally have one or more suitable substituents such as alkoxy (eg methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc.), nitro 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.
  • the compounds of the formula (I) 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, Ti enoic acid, etc. are present.
  • 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, Ti enoic acid, etc. are present.
  • the compounds of the formula (I) used according to the invention allow, for example for double-containing or chiral groups R 1 to R 9 , Xi, Xg, X 9 and 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, balantidiosis, cryptosporidiosis and sarcomocystosis , Akanthamöbose, Naeglerose, Coccidiosis, Giardiosis and Lambliosis.
  • malaria prophylaxis and as a prophylaxis of sleeping sickness and Chagas disease, toxoplasmosis, amoebic dysentery, Leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcolocystosis, acanthambidosis, cocoonosis, and naeglerosis the Giardiose and the Lam- ⁇ bliose suitable.
  • 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 Corynebactercoderobacterium family, pseudoteaculoid bacterium, family of bacteria Genus Mycobacterium, in particular 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 bacteria, in particular the type Lymphia monocytosis Erythipathus, especially the species Logenia, especially the type Logenia tris , Bacteria of the genus Clostridium, bacteria of the
  • Organophosphorus compounds and their derivatives are therefore suitable for the treatment of diphtheria, acne vulgaris, listeriosis, erysipelas in animals, gas burns 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 - 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, Ehrlich
  • the use is also useful in Helicobacter eradication therapy for ulcers of the gastrointestinal tract.
  • 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 substances according to the invention can also be used in particular for infections with the following viruses:
  • Parvoviridae parvoviruses, dependoviruses, densoviruses, adenoviridae: adenoviruses, mastadenoviruses, aviadenoviruses, papovaviridae: papovaviruses, in particular papillomaviruses (so-called wart viruses), polyomaviruses, in particular JC virus, herpes virus, and herpes virus, and virus virus virus, 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, aviviruses, capriviruses, leporipox viruses, all primarily hepatotropic viruses, hepatitis viruses: hepatitis A viruses,
  • Picornaviridae Picornaviruses, all enteroviruses, all polioviruses, all Coxsackieviruses, all echo viruses, all rhino viruses, hepatitis A virus, aphthoviruses, Calciviridae: Hepatitis E virus, Reoviridae: reovirus, Orbi virus, rotavirus, Togaviridae: togaviruses, alphaviruses, rubiviruses, pestiviruses, rubella virus, Flaviviridae: flavivirus, TBE virus , hepatitis C virus, Orthomyxoviridae: All influenza viruses, Paramyxoviridae: paramyxovirus, morbillivirus, pneumovirus, measles virus, mumps virus, Rhabdoviridae: rhabdovirus, rabies virus, Lyssavi- rus, viskuläres stomatitis, Coronaviridae: cor
  • organophosphorus compounds according to the invention are therefore suitable for combating the following viral infections:
  • the compounds described, ie the organophosphorus compounds according to Formula (I) and esters and salts thereof show a strong cytotoxic activity against single and multi-cell parasites, in particular against the pathogens of malaria and sleeping sickness. Accordingly, the compounds according to the 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.
  • unicellular parasites are to be understood as protozoa in accordance with the narrower definition of parasitology.
  • 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", for administration in be prepared in any suitable manner analogous to known anti-infectious agents (mixed with a non-toxic pharmaceutically acceptable carrier).
  • salts of the compounds include salts which form the compounds of the formulas (I) 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.
  • the salts formed by a suitable selection of X 3 and X 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 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, 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.
  • humectants e.g. B. glycerin
  • disintegrant e.g. B. agar-agar, calcium carbonate and
  • 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 e.g. B. polymer substances and waxes can be used.
  • Embedding compounds e.g. B. polymer substances and waxes can be used.
  • the active ingredient (s) can optionally also be in microencapsulated form with one or more of the above-mentioned carriers.
  • 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.
  • Ointments, 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, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, talc and zinc oxide or mixtures of these substances.
  • active ingredient e.g. B. animal and vegetable fats, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silica, 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 sesate oil, glycerol, glycerol formate - Contain furfuryl alcohol, 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 glycol, dimethylformamide,
  • 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 thereof Contain 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 thereof Contain substances.
  • the formulation forms mentioned can also contain colorants, preservatives and odor and taste-improved additives, e.g. B. peppermint oil and eucalyptus oil and sweeteners, e.g. B. saccharin.
  • the active compounds of the formulas (I) should be present 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.
  • organophosphorus compounds in the pharmaceutical compositions can be used in combination with sulfonamide, sulfadoxine, artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, nicazamidolebazol, praziquantilil Pyrantel, tia bendazole, 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).
  • 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 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 each 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.
  • N-methyl-N - [(3-pyridyl) phosphonomethyl] glycinamide 2a 2.02 g (10 mmol) l- (N-methylamino) -l- (3-pyridyl) methylphosphonic acid (according to B. Boduszek , JSWieczorek, J. Prakt. Chemie 328, 627 (1986)) are dissolved in 0.8 ml (10 mmol) of sodium hydrogen carbonate in 30 ml of water. After 0.94 g (10 mmol) of 2-chloroacetamide has been introduced, the mixture is stirred overnight and the suspension is then heated under reflux for 1 h. The resulting almost clear solution is filtered hot.
  • the filtrate is concentrated under reduced pressure, the residue is taken up in a little water and with half-conc. aqueous HC1 adjusted a pH of 4-5. The acid amide 2a is precipitated from the solution with acetone and reacted further without a cleaning step.
  • N-Methyl-N - [(3-pyridyl) -phosphonomethyne-glycine hydroxamate (2) 0.50 g of the crude product 2a are dissolved in 5 ml of water with 0.15 g (2.2 mmol) of hydroxylamine hydrochloride. After 5 d at RT, the mixture is diluted with water and the product 2 is purified in poor yield on an anion exchanger.
  • N-phosphonomethylglycine 1.50 g (8.8 mmol) of N-phosphonomethylglycine is concentrated in 80 ml of absolute ethanol with the addition of 3 drops. Sulfuric acid refluxed for 3 h. After cooling, 10 equivalents of an equimolar mixture of N-methylhydroxylamine hydrochloride and NaOH in water, stir for 20 min and then adjust the pH to 13. The resulting precipitate is collected, dissolved in water, adjusted to pH 8 with HCl and purified on an anion exchange column. The desired hydroxamate 7 is obtained in medium yield.
  • Compound 8 is prepared analogously to the preparation of compound 7 by reacting N-phosphonomethylglycine with N-
  • the activity of the substances is determined in a test system. This system is based on the inhibition of the growth of parasites, bacteria, viruses and fungi in vitro.
  • the inhibition of malaria parasite growth in blood cultures is determined to determine antimalaria activity.
  • microorganisms to be examined can only be examined in animal models.
  • the corresponding models are used here.
  • Substances that show an effectiveness in the in vitro measuring systems are further investigated in in vivo models.
  • the antiparasitic, antiviral, fungicidal or antibacterial activity is further evaluated in the corresponding animal models.
  • Escherichia coli DOXP reductoisomerase was expressed as a recombinant protein in E. coli.
  • the oxidation of ADPH was measured in a spectrophotometer at 365 nm.
  • the activity of the DOXP reductoisomerase was measured in the presence of the compounds 1 to 8 in various concentrations between 0.1 and 100 ⁇ mol l "1. The measured values were used to determine the concentration at which the enzyme is inhibited half-maximally (IC 5 o)
  • the results, ie the IC50 Values are listed in Table 1.
  • the antimalarial activity of substances 1 to 8 was determined on in vitro cultures of the malaria pathogen Plasmodium falciparum.
  • the wells of a 96-well microtiter plate were each loaded with 200 ⁇ l of an asynchronous Plasmodium falciparum culture with 0.4% parasitemia and 2% hematocrit.
  • a serial dilution series of the compounds was then prepared in triplicate between concentrations of 100 to 0.14 ⁇ mol 1 "1.
  • the plates were incubated at 37 ° C., 3% CO 2 and 5% O 2 for a period of 48 hours.
  • 30 ⁇ l of medium supplemented with 27 ⁇ Ci ml of “1 [ 3 H] hypoxanthine were added to each well.
  • the parasites were harvested by filtration on glass fiber filters and the incorporated radioactivity was measured. Inhibition of parasite growth was measured as a percentage inhibition of tritium incorporation. The inhibition of parasite growth was expressed as a percentage inhibition of tritium incorporation based on a comparison without substance. The half-maximum inhibitory concentration (IC50) of the substance was determined by extrapolation of the values.

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

Abstract

Utilisation de composés de formule générale (I) dans laquelle A est choisi dans le groupe constitué de -CR5R6-, -CR5R6CH(OH)-, -CR5R6CO- et -COCR5R6-, pour la fabrication de médicaments destinés au traitement thérapeutique et prophylactique d'infections provoquées par des virus, des bactéries, des champignons et des parasites, chez l'homme et chez l'animal.
PCT/EP2001/006539 2000-06-08 2001-06-08 Utilisation de derives d'acide hydroxamique organophosphores pour la fabrication de medicaments Ceased WO2001093872A1 (fr)

Priority Applications (1)

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AU2001279649A AU2001279649A1 (en) 2000-06-08 2001-06-08 Use of organophosphorous hydroxamic acid derivatives for producing medicaments

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DE10028367 2000-06-08
DE10028367.5 2000-06-08

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010014943A3 (fr) * 2008-08-01 2011-01-13 Bioxiness Pharmaceutics, Inc. Analogues de méthionine, et procédés d'utilisation de ceux-ci
AU2016206369B2 (en) * 2009-12-07 2018-01-18 Cardioxyl Pharmaceuticals, Inc. N-acyloxysulfonamide and n-hydroxy-n-acylsulfonamide derivatives
US9949988B2 (en) 2014-09-12 2018-04-24 Antibiotx 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
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
JP2023129525A (ja) * 2016-04-18 2023-09-14 ビボリョン セラピューティクス エヌブイ メプリンアルファ及びベータの新規な阻害剤

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998050348A1 (fr) * 1997-05-09 1998-11-12 Agouron Pharmaceuticals, Inc. Inhibiteurs de metalloproteases, compositions pharmaceutiques les contenant et leurs utilisations pharmaceutiques
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
WO2000031085A1 (fr) * 1998-11-25 2000-06-02 Jomaa Pharmaka Gmbh Composes phosphororganiques et leur utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998050348A1 (fr) * 1997-05-09 1998-11-12 Agouron Pharmaceuticals, Inc. Inhibiteurs de metalloproteases, compositions pharmaceutiques les contenant et leurs utilisations pharmaceutiques
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
WO2000031085A1 (fr) * 1998-11-25 2000-06-02 Jomaa Pharmaka Gmbh Composes phosphororganiques et leur utilisation

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010014943A3 (fr) * 2008-08-01 2011-01-13 Bioxiness Pharmaceutics, Inc. Analogues de méthionine, et procédés d'utilisation de ceux-ci
US8580859B2 (en) 2008-08-01 2013-11-12 Bioxiness Pharmaceuticals, Inc. Methionine analogs and methods of using same
US9695119B2 (en) 2008-08-01 2017-07-04 Bioxiness Pharmaceuticals, Inc. Methionine analogs and methods of using same
AU2016206369B2 (en) * 2009-12-07 2018-01-18 Cardioxyl Pharmaceuticals, Inc. N-acyloxysulfonamide and n-hydroxy-n-acylsulfonamide derivatives
US10758553B2 (en) 2014-09-12 2020-09-01 UNION therapeutics A/S Antibacterial use of halogenated salicylanilides
US9949988B2 (en) 2014-09-12 2018-04-24 Antibiotx A/S Antibacterial use of halogenated salicylanilides
US11285164B2 (en) 2014-09-12 2022-03-29 UNION therapeutics A/S Antibacterial use of halogenated salicylanilides
US11324761B2 (en) 2014-09-12 2022-05-10 UNION therapeutics A/S Antibacterial use of halogenated salicylanilides
US11331327B2 (en) 2014-09-12 2022-05-17 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
JP2023129525A (ja) * 2016-04-18 2023-09-14 ビボリョン セラピューティクス エヌブイ メプリンアルファ及びベータの新規な阻害剤
JP7739365B2 (ja) 2016-04-18 2025-09-16 ビボリョン セラピューティクス エヌブイ メプリンアルファ及びベータの新規な阻害剤
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

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AU2001279649A1 (en) 2001-12-17

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