SK10552001A3 - Use of phosphororganic compounds for the prophylactic and therapeutical treatment of infections - Google Patents

Abstract

The invention relates to the use of phosphororganic compounds of general formula (I), wherein X is a phosphor atom or a sulphur atom and A is a substituted or an unsubstituted C2-5-alkyl chain, for the therapeutical and prophylactic treatment of infections in humans and animals, whereby said infections are caused by viruses, bacteria, fungi and parasites. Said compounds can also be used in plants as fungicides, bactericides and herbicides.

Description

Technical field

The invention relates to phosphororganic compounds as well as their salts, esters and amides, and their use in the manufacture of medicaments for the therapeutic and prophylactic treatment of human and animal infections caused by viruses, bacteria, fungi and parasites and their use as fungicide, bactericide and herbicide in plants Phosphoric compounds of the invention include phosphinoyl derivatives, phosphinic acid derivatives and phosphonic acid derivatives

BACKGROUND OF THE INVENTION

There remains a strong need to enrich human and animal treatments, as well as to provide plant protection products that not only have potent efficacy but, unlike other medicines or plant protection products, also exhibit fewer side effects and thus pose less health threat to humans

SUMMARY OF THE INVENTION It is therefore an object of the present invention to provide a substance which can be used in infections with viruses, bacteria, fungi and parasites in humans and animals and in plants such as fungicides, bactericides and herbicides, and which satisfies the above conditions.

SUMMARY OF THE INVENTION

This object has been surprisingly solved by a group of substances as defined in claim 1. This group of substances exhibits an antifungal action against viruses, certain bacteria, fungi, monocell and multicellular parasites. · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

The phosphororganic compounds used according to the invention correspond to the general formula (I)

R ₂ '4 in which X is P or S, wherein A is unbranched C 2-9 alkylene chain having substituents which are the same or different and selected from the group consisting of hydrogen, hydroxy, halo, amino and 0x0-, Ci.26-alkylzvyšky, Ci.26 ⁱⁿ alkoxy radicals, C. ₂ 6-alkoxy-26-alkylzvyšky or C 3-8 cycloalkyl- (9) alkyl, wherein each C-26 alkyIzvyšok and each C 26-alkoxy radical may be branched or unbranched, saturated or unsaturated with one or more double bonds and may be substituted by hydroxy-, amino-, halogen- and oxo- and both C3-8-cycloalkyl and C3-8-cycloalkyl- (Co-9) -alkyl groups may have one or more double bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen, or sulfur atoms, and wherein both the cycloalkyl group and the alkyl group may be substituted by hydroxy-, amino-, halogen-, 0x0-, branched or unbranched ( C 1-8 -alkyl or (C 2-9) alkenyl, wherein the C 1-8 -alkyl and the C 2-9 -alkenyl may be substituted by hydrogen-, hydroxy-, halogen-, amino- and 0x0-, wherein R 1 and R 2 are the same or different and are selected from the group pins consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, substituted and unsubstituted aryl , substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen, OX 1 and OX 2, wherein X 1 and X ₂ are the same or different and are selected from the group consisting of: consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heteroc an alkyl radical wherein R ₃ and R ₄ are the same or different and are selected from the group consisting of substituted and unsubstituted C 1-6 -alkyl, hydroxy-C 1-6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aryl; unsubstituted aralkyl, substituted and unsubstituted C1-26 alkenyl, substituted and unsubstituted C1-8. ₂ 6 -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX 3 and OX _4, wherein X ₃ and X ₄ are the same or different and selected from the group consisting of hydrogen, substituted and unsubstituted & 2alkyl - alkyl, substituted and unsubstituted hydroxyl-C ₂ 6 -alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 26-alkenyl, substituted and unsubstituted C ₂ 6 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, silyl, cation of organic and inorganic bases, in particular metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which are derived from ethylenediamine or amino acids and also include pharmaceutically acceptable salts, esters and amides and ester salts

As X 3 and X ₄ are the preferred metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds which derive from ethylene diamine or amino acids, T j form the salt of the compound organophosphorus compounds with organic or inorganic bases (e.g., sodium salt , potassium salt, calcium salt, aluminum salt, ammonium salt, magnesium salt, triethylammonium salt, ethanolamine salt, dicyclo salt, hexylamine, ethylenediamine salt, Ν, Ν'- salt dibenzylethylenediamine, etc.) as well as salts with amino acids (e.g., arginine, aspartic acid, glutamic acid, etc.) and the like

X ₃ and X ₄ are particularly preferably the same or different and selected from the group consisting of hydrogen, sodium, potassium, methyl, ethyl

Preferably, A is a C 3-5 alkyl chain.

Particularly preferred are compounds of formula (II)

XAP R 1 -R ₃ CO,

CH 3 R 4 wherein X, R 1, R 3 and R 4 are as defined above, with R 1 being preferred is substituted on the C-atom adjacent to the heteroatom with a hydroxy group, and a compound of formula (III)

R 1 -XA-P-R ₃

OH

R 4 wherein X, R _b, R ₃ and R ₄ are as defined above, it being preferred that R 1 is an acyl group, especially a formyl, acetyl, propionyl or butyryl group

Compounds with the following structures are also preferred.

n -x-c-c-c-c = I 0 -U I (IV) · I OH I R4 H ^H = C-C-Cl 0 -U I (IN)· I r ₂ I R4 9? 0 II II II -x-c-c-c-c = -P — r ₃ I (VI) · I r ₂ I OH ? ^Η ΐ ABOUT II -x-c-o-c-ci -P — r ₃ | W · r ₂ I OH ? « - ^ - C-C-C-C I O11-C-P-R ₃ (VII) I I OH 1 OH

.Π Π

Ri — X — C — C — C — C — C — P — R 3 θχ),

R ₂

R4 —R3 (x) a

OH

R-R

_IL-2 R UJ

U ^H 7!

R1-X-C-CCC-NO-P-R ₃ (XI) R 4

The particularities of the above definitions and suitable examples thereof are set forth in the following

Acyl is a substituent that is derived from an acid such as an organic carboxylic acid, carbonic acid, carbamic acid, or an individual of the aforementioned corresponding thioacid or imidoacid, or an organic sulfonic acid, which acids include the corresponding aliphatic, aromatic and / or heterocyclic groups in the a molecule as well as carbamoyl or carbamimidoyl Suitable examples for these acyl groups are given in the following:

Aliphatic acyl groups refer to aliphatic acid acyl radicals which include the following alkanoyl (e.g., formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, etc.), alkenoyl (e.g., acryloyl, methacryloyl, crotonoyl, etc.) e.g., methylthioacetyl, ethylthioacetyl, etc.), alkanesulfonyl (e.g., mesyl, ethanesulfonyl, propanesulfonyl, etc.), alkoxycarbonyl (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarboyl, etc.), alkylcarbamyl (N); (N-methyl) -thiocarbamoyl etc.], alkylcarbamimidoyl (e.g. methylcarbamimidoyl etc.), oxalo, alkoxalyl (e.g. methoxalyl, etoxalyl, propoxalyl, etc.) ··· · · ···· · ·· · ··

In the above examples for aliphatic acyl groups, the aliphatic hydrocarbon moiety, especially the alkyl group or the alkane moiety, may have one or more suitable substituents, such as amino, halogen (e.g. fluorine, chlorine, bromine, etc.), hydroxy, hydroxylmino, carboxy, alkoxy (e.g., methoxy, ethoxy, propoxy, etc.), alkoxycarbonyl, acylamino (e.g., benzyloxycarbonylamino, etc.), acyloxy (acetoxy, benzoyloxy, etc.) and the like such as preferred aliphatic acyl radicals with such substituents include, for example, amino, carboxy, amino and carboxy, halogen, acylamino or the like substituted alkanoyls

Aromatic acyl radicals are those derived from an acid having a substituted or unsubstituted aryl group, wherein the aryl group may include phenyl, toluyl, xylyl, naphthyl, and the like. Suitable examples are set forth in the following aroyl (e.g., benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl, etc.), aralkanoyl (e.g., phenylacetyl etc.), aralkenoyl (e.g., cinnamoyl), aryloxyalkanoyl (e.g., phenoxyacetyl, etc.), arythioalkanoyl (e.g., phenythioacetyl 1, etc.), arylaminoalkanoyl (e.g., N-phenylphenyl), benzenesulfonyl, tosyl or toluenesulfonyl, naphthalenesulfonyl, etc.), aryloxycarbonyl (e.g., phenoxycarbonyl, naphthyloxycarbonyl, etc.), aralkoxycarbonyl (e.g., benzyloxycarbonyl, etc.), arylcarbamoyl (e.g., phenylcarbamoyl, naphthylcarbamoyl); arylglyoxyloyl (e.g. phenylglyoxyloyl etc.).

In the above examples for aromatic acyl radicals, the aromatic hydrocarbon moiety (especially the aryl moiety) and / or the aliphatic hydrocarbon moiety (especially the alkane moiety) may optionally have one or more suitable substituents such as those already mentioned as suitable substituents for alkyl or alkane moieties. In particular and as an example for preferred aromatic acyl radicals with particular substituents, mention may be made of halogen and hydroxy or halogen and acyloxy substituted aroyl and hydroxy, hydroxyimino, dihaloalkanoyloxy-substituted aralkanoyl such as arylthiocarbamoyl (e.g. phenylthiocarbamoyl, etc.), arylcarbam ) 9 9 99 99) 9 9 99 99

A heterocyclic acyl radical is an acyl radical derived from an acid having a heterocyclic radical, including a heterocyclic carbonyl in which the heterocyclic radical is an aromatic or aliphatic 5- to 6-membered heterocycle with at least one heteroatom selected from nitrogen, oxygen and sulfur (e.g. thiophenyl) , furoyl, pyrrolecarbonyl, nicotinoyl, etc.), a heterocycle-alkanoyl in which the heterocyclic radical is 5- to 6-membered and has at least one heteroatom selected from nitrogen, oxygen and sulfur [e.g., thiophenylacetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2 amino-4) (thiazolyl) -2-methoxyiminoacetyl, etc.] and the like

In the above examples for heterocyclic acyl radicals, the heterocycle and / or the aliphatic hydrocarbon moiety may optionally have one or more suitable substituents, such as those indicated as suitable for alkyl or alkane groups

Alkyl is a straight or branched chain alkyl radical of up to 26 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like

Hydroxyalkyl is a straight or branched chain alkyl radical of up to 26 carbon atoms having at least one hydroxyl group, preferably one or two hydroxy groups

Alkenyl includes straight or branched chain alkenyl groups of up to 26 carbon atoms unless otherwise defined, such as vinyl, propenyl, (e.g., 1-propenyl, 2-propenyl), 1-methylpropenyl, 2-methylpropenyl, butenyl, 2-ethylpropenyl , pentenyl, hexenyl

Alkynyl includes straight-chain or branched alkynyl groups of up to 26 carbon atoms

Cycloalkyl is especially optionally substituted -cycloalkyl, as possible substituents include, but are not limited to, alkyl, alkenyl, alkynyl,

Alkoxy (e.g., methoxy, ethoxy, etc.), halogen (e.g., fluorine, chlorine, bromine, etc.), nitro, and the like

Aryl is an aromatic hydrocarbon residue such as phenyl, naphthyl, etc., which may optionally have one or more substituents such as alkyl, alkenyl, alkynyl, alkoxy (e.g. methoxy, ethoxy, etc.), halogen (e.g. fluorine, chlorine, bromine etc.), nitro and the like

Aralkyl includes mono-, di-, triphenylalkyls such as benzyl, phenethyl, benzhydryl, trityl and the like, wherein the aromatic moiety may optionally have one or more suitable substituents such as aicoxy (e.g. methoxy, ethoxy, etc.), halogen (e.g. fluorine, chlorine, bromine) etc.) nitro and the like

The residues X3 and _X4 may preferably be selected such that esters form on the phosphinic group or phosphonic group Suitable examples of the esters of the formulas (I) to (XI) are calculated Suitable mono- and di-esters, where the preferred examples of the such esters include alkyl esters (e.g., hexadecanyl ester, octadecanyl, etc.), aralkyl esters (benzyl, phenethyl, benzhydryl, trityl, etc.), aryl esters (e.g., phenyl, tolylester, naphthyl, etc.), aroylalkyl esters (e.g., trialkylsilyl, etc.) 1 h allogene 1 y 1, alkyltralkylalhenylsilyl, diazaryl 1 h and 1-henylsilyl, trialkoxy halogensilyl, dialkylalkyl halosilyl, dialkoxydihalogensilyl, trialkoxyhalogensilyl, etc. ) and so on

In the above esters, the alkane or arene moiety may optionally have at least one suitable substituent, such as halogen, alkoxy, hydroxy, nitro or the like

The compounds of formulas (I) to (XI) used according to the invention can exist in their protonated form as an 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. • e ··· ·

The compounds of formulas (I) to (XI) used according to the invention admit to:

example of the double bond-containing, or chiráíne of R |, _R2, R 3, R 4, X, X _2, X _4, and A, the existence of the stereoisomers use of the compounds of the invention includes all spatial isomers both as pure individual, and also in in the form of mixtures thereof

In humans and animals, phosphororganic compounds are particularly suitable for the therapeutic and prophylactic treatment of infections caused by viruses, bacteria, single-cell and multi-cell parasites and fungi.

The compounds are active against unicellular parasites (protozoa), in particular against malaria and sleeping sickness agents, as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcocystosis, acanthamebosis, acanthamebosis, acanthamebosis, acanthamebosis lambliosis

They are therefore particularly suitable for the prophylaxis of malaria and for the prophylaxis of sleeping sickness, as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcocystosis, acanthamebosis, laegleriosis, coccidiosis, coccidiosis

The active compounds according to the invention can be used in particular against the following bacteria of the family Propionibacteriaceae, in particular of the genus Propionibacterium, in particular of the species Propionibacterium acnes, of the family Actinomycetaceae, in particular of the genus Actinomyces, bacteria of the genus Corynebacterium and Corynebacterium in particular Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium, Chlamydiaceae, in particular Chlamydia trachomatis and Chlamydia psittaci, Listeria, in particular Listeria rocytogenes, Bactelthia bactenamia, Bactenamia species, Bactenamia , Yersinia pseudotuberculosis, Yersmia entrocolitica and Yersinia

9 · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Ruckeri, Mycoplasmataceae, Mycoplasma and Ureoplasma spp., In particular Mycoplasma pneumoniae, Brucella spp., Bordetella spp., Neisseriaceae spp. bacteria of the Vibrionaceae family, in particular of the genera Vibrio, Aeromonas, Plesiomonas and Photobacterium, in particular Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas, Campylobacter species, in particular Campylobacter jejuni species, Campylobacter coli and Helicobobacter fetus, p. bacteria of the family Spirochaetaceae and Leptospiraceae, in particular of the genera Treponema, Borrelia and Leptospira, in particular Borrelia burgdorferi bacteria of the genus Actinobacillus, bacteria of the family Legionellaceae, genus Legionella, bacteria of the family Rickettsiaceae and family Bartonellaceae, bacteria of the genera Nocardia and Rhodococcus, bacteria of the genus Dermatophilus, bacteria of the family Pseudomonad Pseudomonad , Providencia, Salmonella, Serratia and Shigella, bacteria of the family Pasteurellaceae, in particular of the genus Haemophilus, bacteria of the family Micrococcaceae, in particular of the genera Micrococcus and Staphylococcus, bacteria of the family Streptococcaceae, in particular of the genera Streptococcus and Bacillus cactus,

Thus, the phosphororganic compounds and their derivatives are useful in the treatment of diphtheria, Acne vulgaris, listeriosis, animal robin, human and animal gas gas, human and animal paragonimosis, human and animal tuberculosis, leprosy and other mycobacteriosis in human and animal, paratuberous animal, plague, mesenteric lymphadenitis and pseudotuberculosis in human and animal, cholera, legionnaires disease, human and animal borreliosis, human and animal leptospirosis, syphilis, Campylobacter enteritis in human and animal, Moraxella and animal conjunctivitis, animal and animal conjunctivitis, human, spleen in human and animal, actinomycosis in human and animal, streptotrichosis, psittacosis / ornithosis in animals, Q-fever and Ehrlichiosis · · ···· · · ···· · · ···· · · ·· ·

It is also beneficial to use Helicobacter eradication therapy in gastric and intestinal ulcers

Combinations with another antibiotic may be used for the treatment of the above-mentioned diseases. In particular, isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, protonamide and dapson are suitable for the treatment of tuberculosis.

The active compounds according to the invention can be used further in particular in infections with the following viruses

Parvoviridae parvoviruses, dependoviruses, densoviruses, Adenoviridae adenoviruses, mastadenoviruses, aviadenoviruses, Papovaviridae papovaviruses, especially papillomaviruses (so-called wart virus), polyomaviruses, in particular JC-virus, BK virus

Herpesviridae all herpesviruses, in particular Herpes-simplex-viruses, varicela / zoster-viruses, human cytomegalovirus, Epstein-Barr viruses, all human herpesviruses, human herpesvirus 6, human herpesvirus 7, human herpesvirus 8, Poxviridae parapherapy, poxviridae parapherapy, , molluscumcontagiosum-virus, aviviruses, capriviruses, leporipoxviruses, all primary hepatotropic viruses, hepatitis-A-viruses, hepatitis-B-viruses, hepatitis-C-viruses, hepatitis-D-viruses, hepatitis -viruses, hepatitis-G-viruses, Hepadnaviruses all hepatitisviruses Hepatitis-B-virus, hepatitis-D-viruses, Picornaviridae picornaviruses, all enteroviruses, all polioviruses, all coxsackieviruses, all echoviruses, all rhinatitis viruses Calciviridae hepatitis-E-viruses, Reoviridae reoviruses, orbiviruses, rotaviruses, Togaviridae togaviruses, alphaviruses, rubiviruses, pestiviruses, Rub ellavírus, Flaviviridae flaviviruses, FSME virus, hepatitis Cvírus, Orthomyxoviridae all influenza viruses, Paramyxoviridae paramyxoviruses, morbillivirus, pneumovirus, masernvírus, mumps virus, Rhabdoviridae rhabdovirus rabiesvírus, lyssavirus, viskulárny stomatitisvírus, Coronaviridae, coronaviruses, Bunyaviridae, bunyaviruses, nairovirus, phleboviruses, Uukuvirus , hantavirus, hantaanvirus, Arenaviridae arenaviruses, lymphocytic choriomeningitis-virus, Retroviridae retroviruses, all FITL-viruses, human · · · · · · ····

T-cell leukemia virus, oncornaviruses, spumaviruses, lentiviruses, all HIviruses, Filoviridae Marburg- and Ebola-viruses, infections with slow viruses, prions, oncoviruses, leukemia-viruses

The phosphororganic compounds are thus suitable for combating the following viral infections eradication of papilloma viruses for the prophylaxis of tumors, in particular genital tumors caused by papillomaviruses in humans, eradication of JCviruses and BK-viruses, eradication of herpesviruses, eradication of human herpesviruses Capsules to human herpesviruses 8 transplantation, eradication of Eppstein-Barr viruses prior to transplantation, and for the prophylaxis of eppstein-Barr-associated tumors, eradication of hepatitis viruses for the treatment of chronic liver diseases and for the prophylaxis of liver tumors and liver cirrhosis, eradication of coxsackiomyces in patients with coxsackiomyia, immune deficiency viruses in humans and animals, treatment of concomitant infections in AIDS patients, treatment of inflammation respiratory tract viral (larynxpapilómy, hyperplasia, rhinitis, pharyngitis, bronchitis, pneumonia), sensory organs (keratoconjunctivitis), of the nervous system (poliomyelitis, meningoencephalitis, encephalitis, subacute sclerosing panencephalitis SSPE, progressive multifocal leukoencephalopathy, lymphocytic choriomeningitis gastrointestinal tract (stomatitis , gingivostomatitis, oesophagitis, gastritis, gastroenteritis, diarrhea), liver and bile system (hepatitis, cholangitis, hepatocellular carcinoma), lymphatic tissue (mononucleosis, lymphadenitis), hematopoietic organs, pancreatic dermal, labialis, fever blisters, Herpes zoster, shingles), mucous membranes (papillomas, conjunctivapapillomas, hyperplasia, dysplasia), cardiac and vascular blood systems (arteritis, myocarditis, endocarditis, pericarditis ida), kidney and urinary tract, genital organs (anogenital lesions, warts, genital warts, congested condylomas, dysplasia, papillomas, cervical dysplasias, condyloma acuminata, epidermodysplasia verruciformis), musculoskeletal system (myosgia) ··· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Treatment of foot-and-mouth disease, ungulates, Colorado-tick fever, Dengue syndrome, haemorrhagic fever, early summer meningoencephalitis (FSME) and yellow fever

The disclosed compounds, i.e. the phosphororganic compounds of formulas (I) to (XI), and their phosphine group esters and amides, as well as their salts, exhibit potent cytotoxic activity against monocell and multicellular parasites, particularly malaria and sleeping sickness agents. 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 the prophylaxis of diseases caused by viruses, bacteria, parasites and fungi, in particular the prophylaxis of malaria and the prophylaxis of sleeping sickness.

The phosphororganic compounds of the present invention, which generally include pharmaceutically acceptable salts, amides, esters, salts of such an ester, or even compounds which upon application provide the compounds of the present invention as metabolic or degradation products, also called prodrugs, can be prepared for administration by any suitable means. in a manner analogous to a known anti-infective agent (mixed with a non-toxic, pharmaceutically acceptable carrier)

Pharmaceutically acceptable salts of the compounds include those which the compounds of the formulas (I) to (XI) form 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, acid tartaric acid, p-toluenesulfonic acid

Also particularly suitable are the pharmaceutically acceptable salts of X 3 and X ₄ , such as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylammonium salt, dicyclohexylamine salt, and amino acid salts such as arginine salt, salt with aspartic acid, glutamic acid salt ·· ···········

The activity of the substances is determined by a system of experiments. This system is based on measuring the inhibition of the growth of bacteria, parasites, viruses, fungi or plants in vitro. To this end, experimental procedures common to one skilled in the art are used.

For example, for the determination of antimalarial activity, the inhibition of the growth of malaria parasites in blood cultures is determined. Determination of antibacterial activity is based on measurement of inhibition of bacterial growth on nutrient media or in liquid cultures Determination of antiviral activity consists of inhibition of viral element formation in cell cultures on culture media or in liquid cultures

Some microorganisms to be investigated can only be studied in animal models.

Substances exhibiting efficacy in in vitro measurement systems are studied further in in vivo models. Antiparasitic, antiviral, fungicidal or antibacterial activity is further evaluated in animal models.

Screening of herbicidal activity is performed using an algae system and measuring isoprene emission from plants under standard conditions

The pharmaceutical active formulations may be presented in unit dosage form. This means that the formulation is available in the form of discrete particles such as tablets, dragees, capsules, pills, suppositories and ampoules in which the active ingredient content is a fraction or multiple of a single dose. Dosage units may contain, for example, 1, 2, 3 or 4 single doses or / 2, X or Ά single doses A single dose contains the most appropriate amount of active ingredient to be administered when administered, which generally corresponds to half or a third or quarter of the daily dose.

Non-toxic, inert, pharmaceutically acceptable carrier materials are solid, semi-solid, or liquid diluents, fillers, and auxiliaries for formulation of any kind. · · · · · · · · · · ·· · · · · · · · · · · · ·

9 9 ·· · 9 · 9

9

9 9

9

9 9

As pharmaceutical preparations there are mentioned tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays Tablets, dragees, capsules, pills and granules can contain the active substances beside conventional carriers such as (a) fillers and extenders, e.g. starches, milk sugar, raw sugar, glucose, mannitol and silicic acid, (b) binders, e.g. carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, (c) humectants, e.g. glycerol, (d) (g) wetting agents, e.g., quaternary ammonium compounds; (g) wetting agents, e.g., cetyl alcohol; glycerol monostearate; (h) adsorbents, e.g., kaolin; bentonite; and (i) antiadhesives, such as talc, calcium and magnesium stearate, and solid polyethylene glycols, or mixtures thereof; h under (a) to (i)

Tablets, dragees, capsules, pills, and granules may optionally be provided with coatings and shells containing repeating agents and may also be formulated to deliver the active ingredients only or preferentially in a certain part of the intestinal tract, possibly elongated, substances and waxes

The active compound (s) may optionally also exist in microencapsulated form with one or more of the above carriers.

Suppositories may contain, in addition to the active compounds, customary, water-soluble or water-insoluble carriers such as polyethylene glycols, fats such as cocoa butter and higher esters (e.g. Cu-alcohol with C 16 -fatty acid) or mixtures thereof

Ointments, pastes, creams and gels may contain, in addition to the active compounds, customary carriers such as animal and vegetable fats, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide or mixtures thereof.

The powders and sprays may contain, in addition to the active ingredient (s), conventional carriers such as milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures thereof. ··· ··· · · · · · · · · · · · · · · · · · · · · · · · · · 17 ·

Sprays may additionally contain conventional spray propellants such as chlorofluorocarbons

The solutions and emulsions may contain, in addition to the active compounds, customary carriers such as solvents, solubilizers and emulsifiers, for example 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 germ oil, olive oil, castor oil and sesame oil, glycerol, glycerol formal, tetrahydrofurfury alcohol, polyethylene glycols and sorbitan fatty acid esters or mixtures thereof

For parenteral administration, solutions and emulsions may also be available in sterile and blood-isotonic form

The suspensions may contain, in addition to the active compounds, conventional carriers such as liquid diluents, e.g. water, ethanol, propylene glycol, suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitan esters and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and mixtures thereof.

Said formulation forms may also contain coloring agents, preservatives as well as flavor enhancers, e.g., matt oil and eucalyptus oil, and sweeteners, such as saccharin.

The active compounds of the formulas (I) to (XI) are preferably present in the abovementioned pharmaceutical preparations in a concentration of from about 0.1 to 99.5% by weight, preferably from about 0.5 to 95% by weight of the total mixture.

In addition to the compound (s) of formula (I) to (XI), the pharmaceutical preparations may also contain other pharmaceutical active ingredients

The compounds may be used with the substances described to date with antibacterial, antiviral, antifungal and antiparasitic properties. In particular, the compounds which have already been used in therapy or are still in use are particularly suitable for this purpose. · · · · · É é é é é a a a a a a a a a

Rote Liste or Simon / Stille, Antibiotics-Therapy in Clinics and Practice, 9 eds 1998, Schattauer Verlag or under http / www customs treasures / impexp / ruling / harmonization / hrm 129 html on the Internet Especially penicillin derivatives, benzylpenicillin (penicillin G), phenoxypenicillin, isoxazoles, lpenicillin, aminopenicillin, ampicillin, amoxixillin, bacampicillin, carboxypenicillin, ticarcillin, temocillin, acyalaminopenicillins, azlocillin, meslocillin, piperacillin, cefefillin, cefefillin, cefefine, , cefmetazole, latamoxef, flomoxef, cefotaxime group, cefozidime, ceftazidime group, ceftazidime, cefpirome, cefepime, other cephalosporins, cefsulodin, cefoperazone, oral cephalosporins of cefalexin group, cefefoxime, cefefoxime, cefefoxime, axetil, cefetamet, cefotiamhexetil, cefdinir, ceftibuten, other β-lacquer tami antibiotics, carbapenem, imipenem / cilastatin, meropenem, biapenem, aztreonam, β-lactamase inhibitors, clavulanic acid / amoxicillin, clavulanic acid / ticarciline, sulbactam / ampicillin, tazobactam / piperacillin, rolacillin, rolacillin, rolacillin, rolacillin, rolacillin, aminoglycosides, gentamicin, tobramycin, netilmicin, amikacin, spectinomyxin, macrolides, erythromycin, clarithromycin, roxithromycin, azithromycin, dirithromycin, spiramycin, josamycin, glycosinicin, linosamide, fusamycin, clindamycin, clindamycin folic, sulphonamides, Co-trimoxazole, trimethoprim, other diaminopyridine-sulphonamide combinations, nitrofurans, nitrofurantoin, nitrofurazone, gyrase inhibitors (quinolones), norfloxacin, ciprofloxacin, ofloxacin, sparfloxacin, foxloloxacin, loxacinxacin, loxacinxacin, enoxacinacin, enoxacin n, Bay Y3118, nitroimidazoles, antimycobacterial agents, isoniazid, rifampicin, rifabutin, etambutol, pyrazinamide, streptomycin, capreomycin, protionamide, terizidone, dapson, clofazimine, topical antibiotics, bacitracin, canrotinomine, polyrotinomine, polyrotinin, tyrotricin, agents, acyclovir, ganciclovir, azidothymidine, didanosine, zalcitabine, thiacytidine, stavudine, ribavirin, idoxuridine. trifluridine, foscarnet, amantadine, interferons, tibolderivatives, proteinase inhibitors, antifungals, polyenes, amphotericin B, nystatin, natamycin, azoles, azoles for septic therapy, miconazole, ketoconazole, tetracycline · ·· ·······

···· · · · · · · · · · · · · · ·

9

9 9 • 9

9 nazol, fluconazole, UK-109 496, topical azoles, clotrimazole, econazole, isoconazole, oxiconazole, bifonazole, flucytosine, grizeofulvin, cyclopiroxolamine, tolnaphthate, naphthifine, terbinafine, ainorolfine, naphthaquinones, xanthoquinones, betulinic acid, betulinic acid, betulinic acid, betulinic acid, arylaminoalcohols, quinine, quinidines, mefloquine, halofantrine, chloroquine, amodiaquine, acridine, benzonaphthyridine, mepacrine, pyronaridine, dapson, sulfonamides, sulfadoxin, sulfalene, trimethoprim, proguanil, chloroproguanil, pyraminoquinoline, diaminopyrimoline, diaminopyrimidine, diaminopyrimidine, diaminopyrimidine, , clindamycin, norfloxacin, ciprofloxacin, ofloxacin, artemisinin, dihydroartemisinin, 10b artemether, arteether, artesunate, atovachone, suramine, melarsoprole, nifurtmox, sodium stibogluconate, pentamidine, amphotericin mebol, amphotericin mebol, metamoxidicine, diethylcarbamazine, ivermectin, bitionol, oxamnichin, metrifonate, pip erazine, embonate

Furthermore, the phosphororganic compounds may exist in the pharmaceutical compositions in combination with sulfonamide, sulfadoxin, artemisinin, atovachonoin, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, methoxylcyclazole, propycamazoline, doxycyclazine, doxycyclazine, , diethylcarbazine, piperazine, pyrivinum, metrifonate, oxamnichin, bitionol or suramine, or in combination with a plurality of such substances

The manufacture of the above pharmaceutical preparations is carried out in a customary manner according to known methods, for example by mixing the active substance (s) with the carrier substance or substances

Said preparations may be used in humans and animals either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously), intracisternally, intravaginally, intraperitoneally, locally (powders, ointments, drops) and for the treatment of infections in cavities and body cavities. solutions for injection, solutions and suspensions for oral therapy, gels, poured formulations, emulsions, ointments or drops are suitable for ophthalmological and dermatological formulations, silver and other salts, ear drops, eye ointments, powders or solutions In animals can receive • · · ····· · · · 1. · · · ·

.: ..: ·· * also take place in suitable formulations in feed or drinking water Gels, powders, powders, tablets, prolonged-action tablets, premixes, concentrates, granulates, pellets, tablets, boluses may also be used in humans and animals , capsules, aerosols, sprays, inhalants The compounds of the invention may be further incorporated into other carrier materials such as synthetic materials (plastic chains for local therapy), collagen or bone cement.

In general, in both human and veterinary medicine, it has proven advantageous to administer the active compound (s) of formula (I) to (XI) in total amounts of from about 0.05 to about 600, preferably 0.5 to 200 mg, to achieve the desired results. per kg of body weight over 24 hours, optionally in the form of multiple unit doses A single dose contains the active compound (s) in particular in amounts of from about 1 to about 200, most preferably 1 to 60 mg / kg of body weight. the dosage, and depending on the type and body weight of the patient to be treated, the type and severity of the disease, the type of preparation and the administration of the medicament, as well as the time span or interval within which administration takes place

Thus, in some cases it may be sufficient to start with less than the abovementioned amount of active ingredient, while in other cases the amount of active ingredient must be exceeded. The precise determination of the optimal dosage required and the route of administration depends on the specialist's decision according to the invention may be administered to animals in the usual concentrations and preparations together with the feed or feed preparations or in drinking water

Furthermore, the compounds according to the invention can be used excellently as bactericides, fungicides and herbicides in plants.

Claims (7)

1 Use of phosphororganic compounds of general formula (I) R 1 -XAP-R ₃ (1), r ₂ R 4 wherein X is P or S, wherein A is unbranched C ₂ 9-alkylene chain having substituents which are the same or different and selected from the group consisting of hydrogen, hydroxy, halo, amino and oxo, C-6 alkylzvyšky _2, C ₂ _ 6 alkoxy radicals, C. ₂₆ -alkoxy-Ci. ₂ and 6-alkylzvyšky C3.8cykloalkyl- (Co-9) alkyl, wherein each _C-2 6-alkyl radical and each alkoxy radical-2alkyl may be branched or unbranched, saturated or unsaturated with one or more double bonds and may be substituted by hydroxy, amino, halo and oxo, and as C _{3. The} C 3-8 -cycloalkyl- (Co-9) alkyl group may have one or more double bonds and the one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen, or sulfur atoms, both cycloalkyl and cycloalkyl. alkyl group also may be substituted by hydroxy, amino, halo, 0x0-, branched or unbranched alkyl groups, and Ci.g-C ₂ _ ₉ -alkenyl, wherein the C-9-alkyl and _C2-9-alkenyl groups may be substituted hydrogen, hydroxy, halogen, amino and 0x0-, wherein R 1 and R ₂ are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1-6 -9-alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1-9 -alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, Substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals, halogen, OX 1 and OX 2, wherein X 1 and X 2 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-9 -alkyl, substituted and unsubstituted hydroxy-C 1-9 -alkyl, substituted and unsubstituted C 1-9 -alkenyl, substituted and unsubstituted C 1. _9- alkynyl 1, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radicals wherein R 3 and R ₄ are the same or different and are selected from the group consisting of substituted and unsubstituted C1-26-alkyl, hydroxy-C1-26 alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted aralkyl, substituted and unsubstituted C1-26-alkenyl, substituted and unsubstituted C1-26 alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX 3 and OX 4, wherein X 3 and X 4 are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted C 1-6 alkyl. ₂ 6 -alkyl, substituted and unsubstituted hydroxy-C 26-alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted C 26-alkenyl, substituted and unsubstituted C 26alkinyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted a heterocyclic radical, a silyl, an organic and inorganic base cation, in particular a metal of the first, second or third main group of the periodic system, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids, and their pharmaceutically acceptable salts, esters and amides and salts esters for the treatment of infectious processes in humans and animals caused by viruses, bacteria, fungi or parasites and as a fungicide, bactericide or herbicide in plants ·· · The use according to claim 1, wherein A is a C 1-6 -alkyl group having substituents which are the same or different and are selected from the group consisting of hydrogen, hydroxy-, halogen-, amino- and oxo-, C 1-6 -alkyl radicals. , Ci_26alkoxyzvyšky, Ci-26-alkoxy-Ci_26 alkylzvyšky or _C3-.8 cycloalkyl (CO9) -alkyl, wherein each-Ci_26-alkyl radical, and each C ₂ galkoxyzvyšok may be branched or unbranched, saturated or unsaturated with one or more double bonds and is optionally substituted with hydroxy, amino, halo and oxo, and C ₃ as well as -8cykloalkylskupina Co-9-alkyl _C3-.8 cycloalkyl (Co-9) alkyl groups can have one or more double and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen, or sulfur atoms, and wherein both the cycloalkyl group and the alkyl group may be substituted by hydroxy-, amino-, halogen-, 0x0-, branched or unbranched Ymi C 9 -alkyl groups and C 2-9 alkenyl group, wherein the C-9-alkyl and _C2-9-alkenyl group may be substituted by hydrogen-hydroxy-, halo-, amino-, and oxoPoužitie according to claim 1 or claim 2, wherein the phosphororganic compounds correspond to formula (II) R1 AP-R ₃ (II), CH ₃ R4 ·· 9 ···· X, Ri, R 3 and R ₄ are as defined in claim 1, wherein it is preferred that R 1 is substituted on the C-atom adjacent to the heteroatom with a hydroxy group Use according to claim 1 or claim 2, wherein the phosphororganic compounds correspond to formula (III) R1-X A-P — R3 (II |) · OH R 4 wherein X, R 1, R ₃ and R ₄ are as defined in claim 1, wherein it is preferred that R 1 is an acyl group, especially a formyl, acetyl, propionyl or butyryl group The use according to claim 1 or claim 2, wherein the phosphororganic compounds are selected from the group consisting of. y? R1 — XC — C — C — C — P — R ₃ (| V) OH ΐ í R1 — X C — C — C — C — P — R3 (v) R ₂ R4 is clearing .. _R1 -x-c-c-c-c-p-r ₃ (vi)> R 2 OH HO O ·· · · · · · · · · · · · · · · · · · · · · OH (j) _{R 1 -} X - C - C - C - C - P - R ₃ (VII) R ₂ OH Rii-Lc-CCC-P-R ₃ (vili). OH OH HO Q About OH H (j) R1-LC-CC-C-C-P-R ₃ (tx) R ₂ R4 ΐ ^Η Ϊ Rf — XC — CCC — C — P — R ₃ (X) and r ₂ OH O OH Híj) o R -, - X - C - C - C - C - P - Ra (XI) R ₂ R 4 wherein X, R 1, R ₂ , R 3 and R ₄ are as defined in claim 1 and the unspecified carbon atom bonds may be substituted as defined in claim 1 Use according to one of claims 1 to 5 for the treatment of infections caused by bacteria, viruses, fungi or single-cell or multi-cell parasites. The use according to claim 6 for the treatment of infections caused by bacteria selected from the group belonging to the bacteria of the family Propionibacteriaceae, in particular of the genus Propionibacterium, in particular of the species Propionibacterium acnes, bacteria of the family Actinomycetaceae, in particular of the genus Actinomyces Mycobacteriaceae, Mycobacterium spp., in particular Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium, Chlamydiaceae spp. of the genus Yersinia, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia entrocolitica and Yersinia ruckeri, bacteria of the family Mycoplasmataceae, genera Mycoplasma and Ureoplasma, in particular Mycoplasma pneumoniae, bacteria of the genus Brucella, bacteria of the genus Bordetella, bacteria of the family Neisseriaceae, in particular of the genera Neisseria and Moraxella, in particular Neisseria meningrioorris, Aeromonas, Plesiomonas and Photobacterium, in particular Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas, Campylobacter species, in particular Campylobacter jejuni species, Campylobacter coli and Campylobacter fetus, Helicobacter species, in particular Helicobacter pylorie species, Bacteria sp. , Borrelia and Leptospira, in particular Borrelia burgdorferi, bacteria of the genus Actinobacillus, bacteria of the family Legionellaceae, genus Legionella, bacteria of the family Rickettsiaceae and family Bartonellaceae, bacteria genus ov Nocardia and Rhodococcus, bacteria of the genus Dermatophilus, bacteria of the family Pseudomonadaceae, in particular of the genera Pseudomonas and Xanthomonas, bacteria of the family Enterobacteriaceae, in particular of the genera Escherichia, Klebsiella, Proteus, Providencia, Salophilella, Sactatia and Sheremella , in particular of the genera Micrococcus and Staphylococcus, of the family Strepto, coccaceae, in particular of the genera Streptococcus and Enterococcus, and of the family Bacillaceae, in particular of the genera Bacillus and Clostridium, and in Helicobacter eradicatory bowel therapy in intestinal ulcer and gastrointestinal tract therapy Use according to claim 6 for the treatment of infections caused by viruses which are selected from the group consisting of viruses of the genus Parvoviridae, in particular parvoviruses, dependoviruses, densoviruses, viruses of the genus Adenoviridae particularly adenoviruses, mastadenoviruses, aviadenoviruses, papiruses, known as wart viruses), polyomaviruses, especially JC-virus, BK-virus and miopapovaviruses, Herpesviridae viruses, especially Herpes-simplex-viruses, varicela / zoster-viruses, human cytomegalovirus, Epstein-Barr virus, all human herpes viruses, all human herpes viruses, human herpesvirus 7, human herpesvirus 8, viruses of the genus Poxviridae, in particular poxviruses, orthopox-, parapox-, molluscum-contagiosum-virus, aviviruses, capriviruses, leporipoxviruses, primary hepatotropic viruses, in particular hepatitis-virusesA · hepatitis-viruses viruses, hepatitis-C-viruses, hepatitis-D-viruses, hepatitis-E-viruses, hepatitis-F-viruses, hepatitis-G-viruses, Hepadnaviruses in particular all hepatitis viruses such as hepatitis-B-virus, hepatitis-Viruses, viruses of the genus Picornaviridae in particular picornaviruses, all enteroviruses, all polioviruses, all coxsackieviruses, all echoviruses, all rhinoviruses, hepatitis-A-virus, aphtoviruses, viruses of the genus Calciviridae, in particular hepatitis-E-viruses, viruses of the genus Reovirus or rotaviruses, in particular reiviruses, rotaviruses, togaviruses, alphaviruses, rubiviruses, pestiviruses, Rubellavirus, Flaviridae viruses especially flaviviruses, FSME-virus, hepatitis-C-virus, Orthomyxoviridae viruses especially influenza viruses, Paramyxo viridae virus virus virus, virx virus virus virus, viry virus virus virus virus virus virus virus virus , mumpsvirus, Rhabdoviridae, especially rhabdoviruses, rabiesvirus, lyssavirus, viscular stomatitisvirus, Coronaviridae viruses, in particular coro virus, viruses, Bunyaviridae viruses, in particular bunyaviruses, nairovirus, flebovirus, uucvirus, hantavirus , Arenaviridae viruses, in particular arenaviruses, lymphocytic choriomeningitis virus, Retroviridae viruses, in particular retroviruses, all HTL viruses, human T-cell leukemia virus, oncornaviruses, spumaviruses, lentiviruses, all HI-virus viruses, all E-virus viruses, virus-virus viruses virus, slow viruses, prions, oncoviruses and leukemia viruses The use according to claim 6 for the treatment of infections caused by unicellular parasites, namely agents of malaria and sleeping sickness, Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcocystosis, coccorebiosis, acanthamebiosis, acanthamebiosis, acanthamebosis The use according to any one of claims 1 to 9 in a pharmaceutical preparation, wherein the pharmaceutical preparation has an effective content of at least one of the phosphororganic compounds according to one of claims 1 to 5 together with a pharmaceutically acceptable carrier. Use according to claim 10, wherein the pharmaceutical preparation comprises at least one further active ingredient Use according to any one of claims 10 or II, wherein the pharmaceutical preparation comprises as one or more of a compound selected from the group consisting of sulfonamide, sulfadoxin, artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline. proguanil, metronidazole, praziquantil, niclosamide, mebendazole, pyrantel, tiabendazole, diethylcarbazine, piperazine, pyrivinum, metrifonate, oxamnichine, bitionol and suramine • 9 ······ The use according to any one of claims 11 to 12, wherein the pharmaceutical preparation comprises as one or more of a substance selected from the group consisting of penicillin, benzylpenicillin (penicillin G), phenoxypenicillin, isoxazolylpenicillin, aminopenicillin, ampicillin, amoxixillin, bacampicillin, tboxicillinillin. , acyalaminopenicillins, azlocillin, meslocillin, piperacillin, apalcillin, mecilinam, cephalosporins, cefazoline group, cefuroxime group, cefoxitin group, cefoxitin, cefmetazole, latamoxef, flomoxef, cefozimime, cefozaxime, cefotaxime, , cefsulodine, cefoperazone, cephalexin group oralcephalosporins, loracarbef, cefprozil, new extended spectrum oralcephalosporins, cefixime, cefpodoximproxetil, cefuroxime-axetil, cefetamet, cefotiam-hexetil, cefenimem, cefenimem, , biapen, azt reonam, β-lactamase inhibitors, clavulanic acid / amoxicillin, clavulanic acid / ticarcillin, sulbactam / ampicillin, tazobactam / piperacillin, tetracyclines, oxytetracycline, rolitetracycline, doxycycline, minocycline, gentamicin, gentamicin, gentamicin, gentamicin, gentamicin, gentamicin , erythromycin, clarithromycin, roxithromycin, azithromycin, dirithromycin, spiramycin, josamycin, lincosamide, clindamycin, fusidinic acid, glycopeptide antibiotics, vancomycin, tecoplanin, sulfimimimimide, sulfinimycin derivatives, phosphinomycin antioxidants, diaminopyridine sulfonamide combinations, nitrofurans, nitrofurantoin, nitrofurazone, gyrase 5 (quinolones) inhibitors, norfloxacin, ciprofloxacin, ofloxacin, sparfloxacin, enoxacin, fleroxacin, pefloxacin, antimony, lomefloxacin, lomefloamycin, lomefloxacin, lomefloamycin, picine, rifabutin, ethambutol, pyrazine amide, streptomycin, capreomycin, protionamide, terizidone, dapson, clofazimine, topical antibiotics, bacitracin, tyrotricin, polymyxins, neomycin, kanamycin, paromomycin, mucirocillin, antiviricin, aciricin, aziricin, aciricin, aziricin, aciricin, aciricin, aciricin, thiacytidine, stavudine, ribavirin, idoxuridine, trifluridine, foscarnet, amantadine, interferons, tibol-derivatives, proteinase inhibitors, antifungals, polyenes, · · · · · · · · · · · · · · Amphotericin B, nystatin, natamycin, azoles, azoles for septic therapy, miconazole, ketoconazole, itraconazole, fluconazole, UK-109 496, topical azoles, clotrimazole, econazole, isoconazole, oxiconazole, bifonazole, flucytosine, grofulvosine, grize ciclopiroxolamine, tolnaphthate, naphthifine, terbinafine, amorolfine, anthraquinones, betulinic acid, semianthraquinones, xanthones, naphthoquinones, ary lami noalcohols, quinine, c hinidines, mefloquine, halofantrine, chloroquine, amodiaquine, acridine, benzonaphthyridine, mepacrine, pyronaridine, dapson, sulfonamides, sulfadoxine, sulfalene, trimethoprim, proguanil, chloroproguanil, diaminopyrimidines, pyrimidine, pyrimethamine, pyrimethamine, pyrimethamine, primimine, proline , ciprofloxacin, ofloxacin, artemisinin, dihydroartemisinin, 10b artemether, arteether, artesunate, atovaquone, suramine, melarsoprol, nifurtmox, sodium stibogluconal, pentamidine, amphotericin B, metronidazole, tlioquinol mine, tlioquinol mine, bitionol, oxamnichin, metrifonate, piperazine, embonate