Classifications

• • 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
  • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
  • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• • 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
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/12—Antivirals
  • A61P31/14—Antivirals for RNA viruses
  • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
  • A61P31/12—Antivirals
  • A61P31/20—Antivirals for DNA viruses
  • A61P31/22—Antivirals for DNA viruses for herpes viruses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P33/00—Antiparasitic agents
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
  • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
  • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
  • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

• organophosphorus compounds for the prophylactic and therapeutic treatment of infections
• the invention relates to the use of organophosphorus compounds and their salts, esters and amides for 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 include phosphinoyl derivatives, phosphinic acid derivatives and phosphonic acid derivatives.
• the object of the present invention is therefore to provide a substance which can be used in infections by viruses, bacteria, fungi and parasites in humans and animals and as a fungicide, bactericide and herbicide in plants and which fulfills the conditions specified above.
• This object is achieved in a completely surprising manner by using the substance group defined in claim 1.
• This group of substances shows an anti-infectious effect against viruses, certain bacteria, fungi, single and multicellular parasites.
• organophosphorus compounds used according to the invention correspond to the general formula (I):
• X is a phosphorus atom or a sulfur atom
• A is an unbranched C 2 - alkylene chain with substituents which are the same or different and are selected from the group consisting of hydrogen, hydroxyl, halogen, amino and oxo groups, C. 2 6 -alkyl radicals, C 1 -2 6-alkoxy radicals, C_.26-alkoxy-C1.26- alkyl radicals or C 3 -8-cycloalkyl- (Co-9) alkyl groups, each C ⁇ - 2 6-alkyl radical and
• each C 1-26 alkoxy radical may be branched or unbranched and saturated or unsaturated with one or more double bonds and may be substituted with hydroxyl, amino, halogen and oxo groups and both the C 3-8 cycloalkyl group and that C0.9 alkyl group of C 3 .
• Cycloalkyl- (C 0 -9) -alkyl group can have one or more double bonds and one or two carbon atoms of the cycloalkyl group can be replaced by nitrogen, oxygen or sulfur atoms, and both the cycloalkyl group and the alkyl group with hydroxy -, Halogen, amino, oxo groups with branched or unbranched C 9 alkyl groups and C 2-9 alkenyl groups can be substituted, the Ci.g-alkyl groups and C -9 alkenyl groups with hydrogen, hydroxyl, amino -, Halogen and oxo groups can be substituted
• R ⁇ and R 2 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1 . 9 -Al.cyl, substituted and unsubstituted hydroxy-9 C ⁇ - alkyl, substituted and unsubstituted C ⁇ -9 alkenyl, substituted and unsubstituted C ⁇ - 9 alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical, halogen, OXi and OX 2 ,
• Xi and X 2 are the same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted C ⁇ - 9 alkyl, substituted and unsubstituted hydroxy-C ⁇ - 9 alkyl, substituted and unsubstituted C ⁇ -9 alkenyl, substituted and unsubstituted C ⁇ -9 alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical is,
• R 3 and j are the same or different and are selected from the group consisting of substituted and unsubstituted C ⁇ alkyl, hydroxy-C .. 26 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C ⁇ . 26 alkenyl, substituted and unsubstituted C ⁇ . 26 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX 3 and OX t ,
• X 3 and 4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C ⁇ . 26 alkyl, substituted and unsubstituted hydroxy-d- 26 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C ⁇ .
• X 3 and 4 are preferably a metal of the first, second or third main group of the periodic table, ammonium, substituted ammonium, or ammonium compounds which are derived from ethylenediamine or amino acids.
• 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, ethylenediamine salt, N, N'-dibenzylethylenediamine salt etc.
• salts with amino acids for example arginine salt, aspartic acid salt, glutamic acid salt etc.
• X 3 and X 4 are particularly preferably the same or different and selected from the group consisting of hydrogen, sodium, potassium, methyl, ethyl.
• A is preferably a C 3 . 5 alkyl chain.
• R ⁇ is preferably an acyl group, particularly preferably a formyl, acetyl, propionyl or butyryl group.
• Acyl is a substituent derived from an acid, such as from an organic carboxylic acid. re, carbonic acid, carbamic acid or the thioic acid or imidic acid corresponding to the individual above acids, or from an organic sulfonic acid, these acids each comprising aliphatic, aromatic and / or heterocyclic groups in the molecule and 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.
• alkanoyl e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, etc.
• Alkenoyl e.g. acryloyl, methacryloyl, crotonoyl etc.
• Alkoxycarbonyl e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, etc.
• Alkyl carbamoyl e.g. methyl carbamoyl etc.
• N-alkyl thiocarbamoyl
• Alkylcarbamimidoyl e.g. methylcarbamimidoyl etc.
• Oxalo 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 (for example fluorine, chlorine, bromine etc.), hydroxy, hy- droxyimino.
• suitable substituents such as amino, halogen (for example fluorine, chlorine, bromine etc.), hydroxy, hy- droxyimino.
• suitable substituents such as amino, halogen (for example fluorine, chlorine, bromine etc.), hydroxy, hy- droxyimino.
• Aromatic acyl radicals are those acyl radicals which derive from an acid with a substituted or unsubstituted aryl group, where the aryl group can include phenyl, toluyl, xylyl, naphthyl and the like; suitable examples are given below:
• Aroyl e.g. benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl etc.
• Aralkanoyl e.g phenylacetyl etc.
• Aralkenoyl e.g. cinnamoyl etc.
• Aryloxyalkanoyl e.g. phenoxyacetyl etc.
• Arylthioalkanoyl e.g. phenylthioacetyl etc.
• Arylaminoalkanoyl e.g. N-phenylglycyl, etc.
• Arenesulfonyl e.g.
• Aryloxycarbonyl e.g. phenoxycarbonyl, naphthyloxycarbonyl etc.
• Aralkoxycarbonyl e.g. benzyloxycarbonyl etc.
• Arylcarbamoyl e.g. phenylcarbamoyl, naphthylcarbamoyl etc
• aromatic hydrocarbon part in particular the aryl radical
• aliphatic hydrocarbon part in particular the alkane radical
• suitable substituents such as those which are suitable substituents for the alkyl group or the alkane radical have already been specified.
• aromatic acyl radicals with special substituents aroyl substituted with halogen and hydroxy or with halogen and acyloxy and aralkanoyl substituted with hydroxy, hydroxyimino, dihalogenalkanoyloxyimino and arylthiocarbamoyl (eg phenylthiocarbamoyl etc.); Arylcarbamimidoyl (eg phenylcarbamimidoyl etc.).
• a heterocyclic acyl radical is understood to mean an acyl radical which comes from an acid with a heterocyclic group; this includes:
• Heterocyclic carbonyl in which the heterocyclic radical is an aromatic or aliphatic 5- to 6-membered heterocycle with at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (e.g. thiophenyl, furoyl, pyrrole carbonyl, nicotinoyl etc.);
• Heterocycle alkanoyl in which the heterocyclic radical is 5- to 6-membered and has at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (for example thiophenyl-acetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino- 4-thiazolyl) -2-methoxyiminoacetyl etc.) and the like.
• nitrogen, oxygen and sulfur for example thiophenyl-acetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino- 4-thiazolyl) -2-methoxyiminoacetyl etc.
• heterocyclic acyl radicals the heterocycle and / or the aliphatic hydrocarbon part may optionally have one or more suitable substituents, such as the same ones which 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, unless otherwise defined, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like.
• Hydroxylalkyl is a straight or branched chain alkyl radical having up to 26 carbon atoms, unless defined otherwise, 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, unless defined otherwise, such as vinyl, propenyl (e.g. 1-propenyl, 2-propenyl), 1-methylpropenyl, 2-methylpropenyl, butenyl, 2 -Ethylpropenyl, pentenyl, hexenyl.
• Alkynyl includes straight or branched chain alkynyl groups with up to 26 carbon atoms, unless it is defined otherwise.
• Cycloalkyl preferably represents an optionally substituted C 3 . 8- cycloalkyl; Possible substituents include alkyl, alkenyl, alkynyl, alkoxy (eg methoxy, ethoxy etc.), halogen (eg fluorine, chlorine, bromine etc.), nitro and the like.
• Aryl is an aromatic hydrocarbon radical, such as phenyl naphthyl etc., which may optionally have one or more suitable substituents, such as alkyl, alkenyl, alkynyl, alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc. ), Nitro and the like.
• suitable substituents such as alkyl, alkenyl, alkynyl, alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc. ), Nitro and the like.
• Alkyl includes mono-, di-, triphenylalkyls such as benzyl, phenethyl, benzhydryl, trityl and the like, where the aromatic part may have one or more suitable substituents such as alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. Fluorine, chlorine, bromine, etc.), nitro and the like.
• alkoxy e.g. methoxy, ethoxy etc.
• halogen e.g. Fluorine, chlorine, bromine, etc.
• the radicals X 3 and j can preferably be chosen such that esters are formed on the phosphino group or phosphono group.
• suitable examples of such esters according to formulas (I) to (XI) include suitable mono- and diesters, and preferred examples of such esters include alkyl esters (for example hexadecanyl ester, octadecanyl 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.
• trialkylhalosilyl dialkyldihalosilyl, alkyltrihalosilyl, dialkylarylhalosilyl, trialkoxyhalosilyl, dialkylaralkylhalosilyl, dialkoxydihalosilyl, trialkoxyhalosilyl, etc.
• the alkane and / or arene portion can optionally have at least one suitable substituent such as halogen, alkoxy, hydroxy, nitro or the like.
• the compounds of the formulas (I) to (XI) used according to the invention can, in their protonated form, as the ammonium salt of organic or inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, lactic acid, maleic acid, fumaric acid, oxalic acid , Tartaric acid, benzoic acid, etc. are present.
• organic or inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, acetic acid, lactic acid, maleic acid, fumaric acid, oxalic acid , Tartaric acid, benzoic acid, etc. are present.
• the compounds used in the invention of the formulas (I) to (XI) can, for example, containing double bonds or chiral groups Ri, R 2, R 3, R, X ls X 2, X 3, X t or A, the occurrence of spatial isomers for.
• the use of the compounds according to the invention includes all spatial isomers both as pure substances and in the form of their loop.
• organophosphorus compounds are particularly suitable for the therapeutic and prophylactic treatment of infections in humans and animals which are caused by viruses, bacteria, single and multicellular parasites and fungi.
• the compounds are active against unicellular parasites (protozoa), in particular against pathogens of malaria and sleeping sickness as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidosis, cryptosporidiosis, and sarcolocystosis , Akanthamöbose, Naeglerose, Coccidiosis, Giardiosis and Lambliosis.
• malaria prophylaxis and as prophylaxis of sleeping sickness and Chagas disease, toxoplasmosis, amoebic dysentery, Leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcolocystosis, acanthamoebosis, cocoonosis, naeglerosis Giardiosis and Lambliosis.
• the active compounds according to the invention can be used in particular against the following bacteria:
• Bacteria of the Propionibacteriaceae family in particular the Propionibacterium genus, in particular the Propionibacterium acnes species, Actinomycetaceae bacteria, in particular the Actinomyces genus, Corynebacterium bacteria, in particular the Corynebacterium diphteriae and Corynebacterium pseudote family mycobacteria, bacteria the species Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium, bacteria of the Chlamydiaceae family, in particular the species Chlamydia trachomatis and Chlamydia psittaci, bacteria of the genus Listeria, in particular the species Listeria mon- derhrixysiophysiophythropia , Bacteria of the genus Clostridium, bacteria of the genus Yersinia, of the species Yersinia pestis, Yersinia
• Organophosphorus compounds and their derivatives are therefore suitable for the treatment of diphtheria, acne vulgaris, listeriosis, erysipelas in animals, gas fires in humans and animals, para-noise burns in humans and animals, tuberculosis in humans and animals, leprosy and other mycobacteriosis in humans and animals, paratuberculosis in animals, plague, mesenteric lymphadenitis and pseudotuberculosis in humans and animals, cholera, legionnaires' disease, Lyme disease in humans and animals, leptospirosis in humans and animals, syphilis, Campylobacter enteritis in humans and animals, Moraxella keratoconjunc -tivitis and serositis of animals, brucellosis of animals and humans, anthrax in humans and animals, actinomycosis in humans and animals, streptotrichoses, psittacosis / ornithosis in animals, Q fever, Ehr
• the use is also useful in Helicobacter eradication therapy for ulcers of the gastrointestinal tract.
• Combinations 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.
• the active compounds 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 Wartsviruses), Polyomaviruses, in particular JC and Viruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesviruses, Herpesvirus
• organophosphorus compounds according to the invention are therefore suitable for combating the following viral infections:
• the organophosphorus compounds of the formulas (I) to (XI) and esters and A ide thereof on the phosphino group and salts thereof show a strong cytotoxic activity against single and multicellular parasites, in particular against the pathogens of malaria and sleeping sickness.
• the compounds according to the invention can be used for the treatment of infectious diseases which are caused by viruses, bacteria, parasites and fungi in humans and animals.
• the compounds are also suitable for use in preventing diseases caused by viruses, bacteria, parasites and fungi, in particular as malaria prophylaxis and as sleeping sickness prophylaxis.
• organophosphorus compounds according to the invention generally include pharmaceutically acceptable salts, amides, esters, a salt of such an ester, or compounds which, when applied, provide the compounds used according to the invention as metabolites or degradation products, also called “prodrugs", for administration be prepared in any suitable manner analogous to known anti-infectious agents (mixed with a non-toxic pharmaceutically acceptable carrier).
• Pharmaceutically acceptable salts of the compounds include salts which the compounds of the formulas (I) to (XI) used 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.
• inorganic or organic acids such as hydrochloric acid, sulfuric acid, citric acid, maleic acid, fumaric acid, tartaric acid, p-toluenesulfonic acid , form.
• salts which are formed by suitable selection of X 3 and, 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.
• test system 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, or fungi Plants in vitro. For this purpose, test methods are used which are known to the person skilled in the art.
• the inhibition of the growth of malaria parasites in blood cultures is determined to determine the antimalarial 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.
• microorganisms to be examined can only be examined in animal models.
• the corresponding models are used here.
• 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.
• 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. carboxymethyl cellulose, alginates, gelatin, polyvinyl pyrrolidone, (c) Humectants, e.g.
• B. glycerin B. glycerin
• disintegrant e.g. B. agar-agar, calcium carbonate and sodium carbonate
• solution retarders e.g. B. paraffin
• absorption accelerator e.g. B. quaternary ammonium compounds
• wetting agents e.g. B. cetyl alcohol, glycerol monostearate
• adsorbent for. B. kaolin and bentonite
• lubricants e.g. B. talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i).
• the tablets, dragees, capsules, pills and granules can be provided with the customary coatings and casings, optionally containing opacifying agents, and can also be composed such that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, possibly with a delay, where as embedding 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 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 Ci 6 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 Ci 6 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 sesame oil, glycerol, glycerol formalin - hol, 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, oils, especially cottons
• solutions and emulsions can also be used in sterile and blood sotonic form.
• suspensions can contain the usual carriers such as liquid diluents, e.g. B. water, ethyl alcohol, propylene glycol, suspending agents, e.g. B. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth or mixtures of these substances.
• liquid diluents e.g. B. water, ethyl alcohol, propylene glycol
• suspending agents e.g. B. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum hydroxide, bentonite, agar and tragacanth or mixtures of these substances.
• the formulation forms mentioned can also contain colorants, preservatives and odor and taste-improving additives, e.g. B. peppermint oil and eucalyptus oil and sweeteners, e.g. B. saccharin.
• the active compounds of the formulas (I) to (XI) should be present in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5% by weight, preferably about 0.5 to 95% by weight. % of the total mixture.
• the pharmaceutical preparations can also contain further active pharmaceutical ingredients.
• the compounds can be used with previously described substances with antibacterial, antiviral, antimyctoic and antiparasitic properties. These include in particular compounds that have already been used in therapy or are still being used. Substances are particularly suitable for this purpose, which are listed in the Red List or in Simon / Stille, Antibiotic Therapy in Clinic and Practice, 9th Edition 1998 Schattauer Verlag, or at http: /w ⁇ vw.customs.treas.gov/imp -exp / lings / narmoniz / hrml29.html listed on the Internet.
• organophosphorus compounds in the pharmaceutical compositions can be used in combination with sulfonamide, sulfadoxine, artemisinin, atovaquone, quinine, chloroquine, hydroxylchloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, nicazolantil, prazoliquilil, praziquantilil Pyrantel, tiabendazole, diethyl carbazine, piperazine, pyrivinum, metrifonate, oxamniquin, bithionol or suramin or more of these substances are present.
• the pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. B. by mixing the active ingredient (s) with the carrier (s).
• the preparations mentioned can either be oral, rectal, parenteral (intravenous, intramuscular, subcutaneous), intracisternal, intravaginal, intraperitoneal, local (PU der, ointment, drops) and for the treatment 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 formulas (I) to (XI) in total amounts of from about 0.05 to about 600, preferably 0.5 to 200 mg / kg Body weight per 24 hours, _ if necessary in the form of several individual 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 above-mentioned amount of active ingredient In some cases it may be sufficient to make do with less than the above-mentioned amount of active ingredient, while in other cases the above-mentioned amount of active ingredient has to be exceeded.
• the person skilled in the art can determine the optimum dosage and type of application of the active ingredients required on the basis of his specialist knowledge.
• 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 according to the invention can be used outstandingly as bactericides, fungicides and herbicides in plants.

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• 1999
  • 1999-01-26 DE DE19902924A patent/DE19902924A1/de not_active Ceased
• 2000
  • 2000-01-25 CZ CZ20012584A patent/CZ20012584A3/cs unknown
  • 2000-01-25 WO PCT/EP2000/000542 patent/WO2000044358A2/de not_active Application Discontinuation
  • 2000-01-25 HU HU0105310A patent/HUP0105310A3/hu unknown
  • 2000-01-25 AU AU24399/00A patent/AU2439900A/en not_active Abandoned
  • 2000-01-25 EP EP00902630A patent/EP1146880A2/de not_active Withdrawn
  • 2000-01-25 CA CA002360661A patent/CA2360661A1/en not_active Abandoned
  • 2000-01-25 TR TR2001/02151T patent/TR200102151T2/tr unknown
  • 2000-01-25 JP JP2000595662A patent/JP2002535354A/ja active Pending
  • 2000-01-25 IL IL14411500A patent/IL144115A0/xx unknown
  • 2000-01-25 SK SK1055-2001A patent/SK10552001A3/sk unknown
  • 2000-01-25 CN CN00803129A patent/CN1337881A/zh active Pending
  • 2000-01-25 PL PL00349910A patent/PL349910A1/xx not_active Application Discontinuation
• 2001
  • 2001-07-25 NO NO20013651A patent/NO20013651L/no not_active Application Discontinuation

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