EP1146880A2

EP1146880A2 - Use of phosphororganic compounds for the prophylactic and therapeutical treatment of infections

Info

Publication number: EP1146880A2
Application number: EP00902630A
Authority: EP
Inventors: Hassan Jomaa
Original assignee: Jomaa Pharmaka GmbH
Current assignee: Bioagency AG
Priority date: 1999-01-26
Filing date: 2000-01-25
Publication date: 2001-10-24
Also published as: SK10552001A3; CN1337881A; HUP0105310A3; NO20013651D0; TR200102151T2; WO2000044358A3; WO2000044358A2; CZ20012584A3; DE19902924A1; NO20013651L; JP2002535354A; IL144115A0; PL349910A1; HUP0105310A2; AU2439900A; CA2360661A1

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

Use of 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 . According to the invention, the organophosphorus compounds include phosphinoyl derivatives, phosphinic acid derivatives and phosphonic acid derivatives.

There is a strong need to provide means for the enrichment of the treatment of humans and animals and the protection of plants which are not only highly effective but also, in contrast to other medicinal products or crop protection agents, have reduced side effects and thus a lower health risk for mean to people.

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.

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

0 0

II II R1-X-A-P-R3 (I)

1 I

R ₂ R ₄

in which X is a phosphorus atom or a sulfur atom,

wherein 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 Cι- ₂ 6-alkyl radical and

REPLACEMENT BLAπ (RULE 26) 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 . _8- 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

in which 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 Cι- alkyl, substituted and unsubstituted Cι _-9 alkenyl, substituted and unsubstituted Cι- 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 ,

where Xi and X _{2 are the} same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted Cι- ₉ alkyl, substituted and unsubstituted hydroxy-Cι- ₉ alkyl, substituted and unsubstituted Cι _-9 alkenyl, substituted and unsubstituted Cι _-9 alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical is,

in which 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 Cι. ₂₆ alkenyl, substituted and unsubstituted Cι. ₂₆ -alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX ₃ and OX _t ,

where X ₃ and _{4 are the} same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted Cι. ₂₆ alkyl, substituted and unsubstituted hydroxy-d- ₂₆ alkyl, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted Cι. ₂₆ -alkenyl, substituted and unsubstituted C.-26-alkynyl, substituted and unsubstituted cycloalkyl, substituted- tem and unsubstituted heterocyclic radical, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic table, ammonium, substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids, and their pharmaceutical acceptable salts, esters and amides and salts of the esters.

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. Ie there are 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, ethylenediamine salt, N, N'-dibenzylethylenediamine salt etc.) and salts with amino acids (for example arginine salt, aspartic acid salt, glutamic acid salt 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.

A is preferably a C ₃ . ₅ alkyl chain.

Compounds of the formula (II) are particularly preferred

0 0 II II R1-X-A-P-R3 (I I),

1 1 CH ₃ R ₄

where X, Rj, R ₃ , »are as defined above, where Rj is preferably substituted by a hydroxyl group on the C atom adjacent to the heteroatom,

and compounds of the formula (III)

0 0

R1-X-A-P-R3 (I I I), I I

OH R ₄

where X, Ri, R ₃ , ι are as defined above, wherein R _{\ is} preferably an acyl group, particularly preferably a formyl, acetyl, propionyl or butyryl group. Compounds with the following structures are also preferred:

0 0 0 II II II

R ₁ -XCCCCPR ₃ (IV),

1 I

OH R

0 OH 0 II I II

R1-X-C-C-C-C-P-R3 (V),

1 IR _{2 4}

0 0 0

II 11 II

Ri -XCCCCPR ₃ (vi:

R ₇ OH

0 HO 0

R ₁ -XCCCCPR ₃ ; vn),

I I

R ₂ R ₄

0 0 0 0

II II II II

R1-X-C-C-C-C-C-P-R3 (VIII),

OH OH

0 OH HO 0

II I 1 11

R1-X-C-C-C-C-C-P-R3 (IX),

IIR ₂ R ₄

0 OH 0 0

II I II II

R ₁ -XCCCCCPR ₃ (X) and

R ₂ OH

0 0 HO 0 II II I II

R1-XCCCCCPR ₃ (XI).

1 I

OH R 4

Special features of the above definitions and suitable examples are given below:

"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.

Suitable examples of these acyl groups are given below.

Aliphatic acyl groups are acyl radicals derived from an aliphatic acid, which include the following: alkanoyl (e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl, etc.); Alkenoyl (e.g. acryloyl, methacryloyl, crotonoyl etc.); Alkylthioalkanoyl (e.g. methylthioacetyl, ethylthioacetyl etc.); Alkanesulfonyl (e.g. mesyl, ethanesulfonyl, propanesulfonyl, etc.); Alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, etc.); Alkyl carbamoyl (e.g. methyl carbamoyl etc.); (N-alkyl) thiocarbamoyl (e.g. (N-methyl) thiocarbamoyl etc.); Alkylcarbamimidoyl (e.g. methylcarbamimidoyl etc.); Oxalo; Alkoxalyl (e.g. methoxalyl, ethoxalyl, propoxalyl etc.).

In the above examples of aliphatic acyl groups, 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. 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.

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 (eg 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.). In the above examples of aromatic acyl radicals, the aromatic hydrocarbon part (in particular the aryl radical) and / or the aliphatic hydrocarbon part (in particular the alkane radical) may optionally have one or more suitable substituents, such as those which are suitable substituents for the alkyl group or the alkane radical have already been specified. In particular and as an example of preferred 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.

In the above examples of 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.

"Aralkyl" 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.

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. from trialkylhalosilyl, dialkyldihalosilyl, alkyltrihalosilyl, dialkylarylhalosilyl, trialkoxyhalosilyl, dialkylaralkylhalosilyl, dialkoxydihalosilyl, trialkoxyhalosilyl, etc.) and the like.

In the above ester, 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.

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.

The 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.

They are therefore particularly useful as 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 pseudotuberculosis, Yersinia enterocolitica and Yersinia ruckeri, bacteria of the family Mycoplasmataceae, of the genera Mycoplasm a and ureaplasma, in particular the species Mycoplasma pneumoniae, bacteria of the genus Brucella, bacteria of the genus Bordetella, bacteria of the Neisseria family, in particular the Neisseria and Moraxella species, in particular the Neisseria meningitides, Neisseria gonorrhoeae and Moraxella bovis species, bacteria of the Vi family brionaceae, in particular of the genera Vibrio, Aeromonas, Plesiomonas and Photobacterium, in particular the species Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonici- das, bacteria of the genus Campylobacter, in particular the species Campylobacter jejuni, Campylobacter coli and Campylobacter fetus, bacteria of the genus Helicobacter, in particular the species Helicobacter pylori, bacteria of the families Spirochaetaceae and Leptospiraceae, in particular of the genera Treponema, Borrelia and Leptospira, in particular Borrelia burgdorferi, bacteria of the genus Actinobacillus bacteria, of the 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 Pseudomonadaceae, in particular the genera Pseudomonas and Xanthomonas, bacteria of the family Enterobacteriaceae, especially the genus Escherbsila Proteus, Providencia, Salmonella, Serratia and Shigella, bacteria of the Pasteurellaceae family, in particular of the genus Haemophilus, bacteria of the Micrococceae family, especially of the genera Micrococcus and Staphylococcus, bacteria of the Streptococcaceae family , in particular the genera Streptococcus and Enterococcus and bacteria of the family Bacillaceae, in particular the genera Bacillus and Clostridium.

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, Ehrlichiosis.

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. For combination preparations with other anti-infectives, 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 -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: poxviruses, orthopox, parapox, molluscum contagiosum virus, aviviruses, capriviruses , Leporipox viruses, all primarily hepatotropic viruses, hepatitis viruses: hepatitis A viruses, hepatitis B viruses, hepatitis C viruses, hepatitis D viruses, hepatitis E viruses, hepatitis F viruses, hepatitis viruses G viruses, hepadnaviruses: all hepatitis viruses, hepatitis B virus, hepatitis D viruses, Picornaviridae: Picornaviruses, all enteroviruses, all polioviruses, all Coxsackieviruses, all echoviruses, all rhinoviruses, hepatitis A virus, aphthiroviruses, calc. Hepatitis E viruses, reoviridae: reoviruses, orbiviruses, rotaviruses, Togaviridae: togaviruses, alphaviruses, rabiviruses, pestiviruses, rubella virus, flaviviridae: flaviviruses, TBE virus, hepatitis C virus, orthomyxoviroviriruses: alleomyxovirus viruses , Morbillivirus, pneumovirus , Measles virus, mumps virus, rhabdoviridae: rhabdoviruses, rabies virus, lyssavirus, viscous stomatitis virus, coronaviridae: coronaviruses, bunyaviridae: bunyaviruses, nanoviruses, arviraviruses, arviraviruses, virus virus, hanavirus virus, hanavirus virus, hanavirus virus virus : Retroviruses, all HTL viruses, human T-cell leukemia virus, oncornaviruses, spuma viruses, lentiviruses, all HI viruses, Filoviridae: Marburg and Ebola viruses, slow virus infections, prions, oncoviruses and leukemia viruses.

The organophosphorus compounds according to the invention are therefore suitable for combating the following viral infections:

Eradication of papillomaviruses for the prevention of tumors, in particular tumors of the genital organs caused by papillomaviruses in humans, eradication of JC viruses and BK viruses, eradication of herpes viruses, eradication of human herpes viruses 8 for the treatment of Kaposi's sarcoma, eradication of cytomegaloviruses Transplants, eradication of Eppstein-Barr viruses before transplantation and for the prevention of Eppstein-Barr virus-associated tumors, eradication of hepatitis viruses for the treatment of chronic liver diseases and for the prevention of liver tumors and liver cirrhosis, eradication of Coxsackieviruses in cardiomyopathies, eradication Coxsackieviruses in diabetes mellitus patients, eradication of immunodeficiency viruses in humans and animals, treatment of concomitant infections in AIDS patients, treatment of inflammation of the viral genesis of the respiratory tract (laryngeal papillomas, hyperplasia, rhinitis, pharyngitis, bronchitis, pneumonia), the Sensory care ane (keratoconjunctivitis), of the nervous system (poliomyelitis, meningoencephalitis, encephalitis, subacute sclerosing panencephalitis, SSPE, pro- sive multifocal leukoencephalopathy, lymphocytic choriomeningitis), of the gastrointestinal tract (stomatitis, gingivostomatitis, oesophagitis, gastritis, gastroenteritis, diarrhea), the liver and the biliary system (hepatitis, cholangitis, hepatocellular carcinoma), the lymphatic tissue (mononucleosis, lymphadenitis), the hematopoietic system, the genital organs (mumps orchitis), the skin (warts, dermatitis, pes labialis, cold sores, herpes zoster, shingles), the mucous membranes (papillomas, connecting apapillomas, hyperplasias, dysplasias), the cardiovascular system (arteritis, myocarditis, endocarditis, pericarditis), the kidney-urinary system, the genital organs (Anogenital lesions, warts, genital warts, pointed condylomas, dysplasias, papillomas, cervical dysplasias, condylomata acuminata, epidermodysplasia verruciformis), the movement organs (myositis, myalgias), treatment of foot and mouth disease of the cloven-hoofed animals, the Colorado syndrome tick, the Colorado syndrome tick , hemorrhagic fever, early summer meningoencephalitis (TBE) and yellow fever.

The connections described, i.e. 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. Accordingly, 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.

The organophosphorus compounds according to the invention, these 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.

Also particularly pharmaceutically suitable are the 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.

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.

For example, 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.

Some of the 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, (d) disintegrant, e.g. B. agar-agar, calcium carbonate and sodium carbonate, (e) solution retarders, e.g. B. paraffin and (f) absorption accelerator, e.g. B. quaternary ammonium compounds, (g) wetting agents, e.g. B. cetyl alcohol, glycerol monostearate, (h) adsorbent, for. B. kaolin and bentonite and (i) lubricants, e.g. B. talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under (a) to (i).

The tablets, dragees, capsules, pills and granules can be provided with the customary coatings and casings, optionally containing opacifying agents, and can also be composed such that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, possibly with a delay, where as embedding 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.

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.

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.

In addition to the active ingredient (s), 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.

For parenteral administration, the solutions and emulsions can also be used in sterile and blood sotonic form.

In addition to the active ingredient (s), 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.

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.

In addition to the compounds of the formulas (I) to (XI), 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: /wΛvw.customs.treas.gov/imp -exp / lings / narmoniz / hrml29.html listed on the Internet. In particular, the derivatives with penicillin, benzylpenicillin (Penicillin G), phenoxypenicillin, isoxazolylpenicillin, aminopenicillin, ampicillin, amoxixillin, bacampicillin, carboxypenicillin, ticarcillin, temocillin, acyalaminopenicillin, apezlillillin, pezlocillin, azizillillin, azecillinillin - group, cefuroxime group, cefoxitin group, cefoxitin, cefotetan, cefmetazole, latamoxef, flomoxef, cefotaxim group, cefozidim, ceftazidim group, ceftazidim, cefpirom, cefepim, other cefalosporinos, cefalodinosine cefalosine cefalosporin cefalosporin Gruppe, Loracarbef, Cefprozil, new oral cephalosporins with extended spectrum, Cefixim, Cefpodoxim-Proxetil, Cefuroxim-Axetil, Cefetamet, Cefotiam-Hexetil, Cefdinir, Ceftibuten, other ß-Lactam antibiotics, Carbapenememilil, Imipenemil , Aztreonam, ß-lactamase inhibitor, clavulanic acid / amoxicillin, clavulanic acid / ticarcillin, sulbactam / ampicillin, tazobactam / pipe racillin, tetracycline, oxytetracycline, rolitetraxyxlin, doxycycline, minocycline, chloramphenicol, aminoglycosides, gentamicin, tobramycin, netilmicin, amikacin, spectinomyxin, macrolides, erythromycin, clarithromycin, ro- xithromycin, azithromycin, dirithromycin, spiramycin, josamycin, lincosamides, clindamycin, fusidic acid, glycopeptide antibiotics, vancomycin, tecoplanin, pristinamycin derivatives, fosfomycin, antimicrobial folic acid antagonists, sulfonamides, di-trimopyrimidonimone, n-trimopyrimidoximidone combinations, other trimimidopyrimidone, sulfonamides, trimidopyrimidoximidone combinations, trimidopyrimidoximidone combinations, other tri-trimopyrimidoximidone combinations, trimidopyrimidoximidone combinations Nitrofurantoin, nitrofurazone, gyrase inhibitors (quinolones), norfloxacin, ciprofloxacin, ofloxacin, sparfloxacin, enoxacin, fleroxacin, pefloxacin, lomefloxacin, Bay Y3118, nitroimidazole, antimycomycinidine, antimycomycinidin, antimycobidin, rimimobinobenzirin, antimycobidin, antimycobinamine, antimycobin, rimimobinocytin , Prothionamide, terizidone, dapsone, clofazimin, local antibiotics, bacitracin, tyrothricin, polymyxins, neomycin, kanamycin, paromomycin, mupirocin, anti-viral agents, acyclovir, ganciclovir, azidothymidine, didanosine, zalcitidine, thidifinurin, thioditinurin, thiocitidine, ribocinidine, thiidocinidine, thiidocinidine, thiidocinidine, thiocinidine, thiocinidine, thiocinidine, thiocinidine, thiocinidine, thiocinidine, thiocytidine, thiocinidine, thiocinidine, thiocinidine, thiocinidine, thiocinidine, thiocididine, thi, Foscarnet, amantadine, interferons, tibol derivatives, proteinase inhibitors, Antifungals, polyenes, amphothericin B, nystatin, natamycin, azoles, azoles for septic therapy, miconazole, ketoconazole, itraconazole, fluconazole, UK-109,496, azoles for topical use, clotrimazole, econazole, isoconazole, biconazole , Flucytosine, griseofulvin, ciclopiroxolamine, tolnaftat, naftifin, terbinafine, amorolfine, antrachinones, betulinic acid, semianthraquinones, xanthones, naphthoquinones, aryamino alcohols, quinine, quinidines, mefloquine, halofanidinodonone, halofantrinone, chlorine Sulfonamides, sulfadoxin, sulphene, trimethoprim, proguanil, chlorproguanil, diaminopyrimidines, pyrimethamine, primaquine, aminoquinolines, WR 238,605, tetracycline, doxycycline, clindamycin, norfloxacin, ciprofloxacin, ofloxacin, dihydroartinisemin, artemisartininem - tesunate, atovaquone, suramin, melarsoprol, nifurtmox, stibogluconate sodium, pentamidine, amphotericin B, metronidazole, clioquinol, mebendazole, Ni closamid, praziquantel, pyrantel, tiabendazole, diethylcarbamazine, ivermectin, bithionol, oxamniquin, metrifonate, piperazine, embonate.

Furthermore, the 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).

In humans and animals, 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. For local therapy, ophthalmic and dermatological formulations, silver and other salts, ear drops, eye ointments, powder or solutions can be used. In animals, 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. Furthermore, 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.

In general, both in human and in veterinary medicine, it has proven to be advantageous to use 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. However, it may be necessary to deviate from the doses mentioned, 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 administration of the drug, and the period or interval within which the administration takes place.

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.

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

Claims

claims

1. Use of organophosphorus compounds of the general formula (I)

0 0 ιι n

R1-X-A-P-R3 (I)

I I

R ₂ R ₄

in which X is a phosphorus atom or a sulfur atom,

wherein A is a C _2-9 alkylene chain with substituents that are the same or different and are selected from the group consisting of hydrogen, hydroxyl, halogen, amino and oxo groups, Cι. ₂₆ -alkyl radicals, Cι. 6-alkoxy radicals, Cι. ₂₆ -alkoxy-Cι. ₂₆ -alkyl radicals or C ₃ . ₈ -Cycloalkyl- (Co- ₉ ) alkyl groups, each Cι. ₂₆ - alkyl radical and each C ₁ . ₂₆ - Alkoxy radical branched or unbranched and saturated or with one or more

Double bonds can be unsaturated and can be substituted with hydroxyl, amino, halogen and oxo groups and both the C ₃ . _8- cycloalkyl group as well as the C ₀ . ₉ - C ₃ alkyl group. ₈ cycloalkyl (C _0. _9,) alkyl group may have one or more double bonds and one or two carbon atoms of the cycloalkyl group by nitrogen, oxygen or sulfur atoms may be replaced, and both the

Cycloalkyl group and the alkyl group of hydroxy, halo, amino, oxo groups with branched or unbranched Cj.g alkyl groups and C ₂ - ₉ - alkenyl groups may be substituted, said Ci.g alkyl groups and C. ₂ ₉ - Alkenyl groups can be substituted with hydrogen, hydroxyl, amino, halogen and oxo groups

in which Ri 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- ₉ -C alkyl, substituted and unsubstituted C.- ₉ alkenyl, substituted and unsubstituted. 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 ,

wherein Xi and X _{2 are the} same or different and is selected from the group consisting of hydrogen, substituted and unsubstituted. ₉ - alkyl, substituted and unsubstituted hydroxy-C ^ -. Alkyl, substituted and unsubstituted C ₁ - ₉ - alkenyl, substituted and unsubstituted. ₉ - alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted Cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical,

in which R ₃ and R ₄ are the same or different and are selected from the group consisting of substituted and unsubstituted C ₁ -, hydroxy-Cι- ₂₆ alkyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted alkyl, and - ₂₀ unsubstituted aralkyl, substituted and unsubstituted Cι- ₂₆ alkenyl, substituted and unsubstituted C ₁ - ₂₀ - alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic radical, halogen, OX ₃ and OX4 consists,

where X ₃ and are the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted Cι. ₂₆ - alkyl, substituted and unsubstituted _{hydroxy-Cι-6} alkyl 2, substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted d- ₂₆ -

Alkenyl, substituted and unsubstituted C ₁ - ₂₆ - alkynyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted heterocyclic residue, a silyl, a cation of an organic and inorganic base, in particular a metal of the first, second or third main group of the periodic system, ammonium nium , substituted ammonium and ammonium compounds derived from ethylenediamine or amino acids. and their pharmaceutically acceptable salts, esters and amides and salts of the esters for the treatment of infectious processes in humans and animals which are caused by viruses, bacteria, fungi or parasites and as a fungicide, bactericide or herbicide in plants.

2. Use according to claim 1, characterized in that AC _3rd ₅ -alkyl group is substituted by substituents which are the same or different and are selected from the group consisting of hydrogen, hydroxyl, halogen, amino and oxo groups, C.- ₂₆ -alkyl radicals, Ci. ₂₆ -alkoxy radicals, Cι.26-alkoxy-Cι- ₆ alkyl radicals or C _3-8 cycloalkyl- (C ₀ - ₉ ) - alkyl groups, each C .. ₂₆ - alkyl radical and each C.- ₂₆ alkoxy radical branched or unbranched and saturated or unsaturated with one or more double bonds and can be substituted with hydroxyl, amino, halogen and oxo groups and both the C ₃ . _8- cycloalkyl group as well as the Co- _9- alkyl group of C ₃ . ₈ - 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 where both the cycloalkyl group and the alkyl group with hydroxy, Halogen, amino, oxo groups can be substituted with branched or unbranched C ₉ alkyl groups and C ₂ - ₉ alkenyl groups can, wherein the 9-alkyl groups and C ₂ - ₉ - alkenyl groups having from hydrogen, hydroxy, amino, halogen and oxo groups may be substituted.

3. Use according to claim 1 or claim 2, characterized in that the organophosphorus compounds of the formula (II)

0 0 II II R1-X-A-P-R3 (I I)

I 1

CH ₃ R

corresponds, wherein X, Ri, R ₃ , i are as defined in claim 1, wherein Ri is preferably substituted on the C atom adjacent to the hetero atom with a hydroxyl group.

4. Use according to claim 1 or claim 2, characterized in that the organophosphorus compounds of the formula (III)

0 0

II 11

R1-X-A-P-R3 (I II)

1 I OH R ₄

corresponds, where X, Rj, R, * are as defined in claim 1, wherein Ri is preferably an acyl group, particularly preferably a formyl, acetyl, propionyl or butyryl group.

5. Use according to claim 1 or claim 2, characterized in that the organophosphorus compounds are selected from the group consisting of

0 0 0

II II 11

R1-X-C-C-C-C-P-R3 (IV),

1 I OH R ₄

0 OH 0 II I II

R1-X-C-C-C-C-P-R3 (V),

1 IR ₂ R ₄

O O O

R ₁ -XCCCC- P-R3 (VI), II

R ₂ OH 0 HO 0

II I II

R1-X-C-C-C-C-P-R3: VID

R ₂ R ₄

0 0 0 0

II II II II

R1-X-C-C-C-C-C-P-R3 (vin;

I I

OH OH

0 OH HO 0 I II

Ri-XCCCCCPR. (IX)

0 OH 0 0

II I II II R1-X-C-C-C-C-C-P-R3 (X) and

R ₂ OH

0 0 HO 0 II II I II

R _ι -xcccccpR ₃ (xi:

1 I OH R ₄

exists, wherein X, Ri, R ₂ , R ₃ and Rj have the meaning defined in claim 1 and the undefined valences of the carbon atoms can be substituted, as defined in claim 1.

6. Use according to one of claims 1 to 5 for the treatment of infections caused by bacteria, viruses, fungi or single or multicellular parasites.

7. Use according to claim 6 for the treatment of infections caused by bacteria selected from the group consisting of bacteria from the Propionibacteriaceae family, in particular the Propionibacterium genus, in particular the Propionibacterium acnes species. Bacteria of the Actinomycetaceae family, in particular of the Actinomyces genus, bacteria of the Corynebacterium genus, in particular the Corynebacterium diphteriae and Corynebacterium pseudotuberculosis species, bacteria of the Mycobacteriaceae family of the Mycobacterium genus, in particular the species

Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and My- cobacterium 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 monocytogenes, bacteria of the species Erysipelthrix rhusiopathiae, bacteria of the genus Clostridium, bacteria of the genus Yersinia nia piesestia species , Yersinia pseudotuberculosis, Yersinia enterocolitica and Yersinia ruckeri,

Bacteria of the Mycoplasmataceae family, of the genera Mycoplasma and Ureaplasma, in particular the species 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 the species Neisseria meningitides, Neisseria gaxorrellaeae Bacteria of the Vibrionaceae family, in particular the Vibrio, Aeromonas, Plesiomonas and Photobacterium genera, in particular the Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas species, Campylobacter bacteria, in particular the Campylobacter jejuni species, Campylobacter coli and Campylobacter fetus, bacteria of the genus , especially the Helicobacter pylori species, bacteria of the Spirochaetaeeae 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, of the genus Legionella, bacteria of the family Rickettsiaceae and family Bartonellaceae, bacteria of the genera Nocardia, Bacteria, and Rhodilungus deratocungia and Rhodocungia and Rhodocungia the family Pseudomonadaceae, in particular the genera Pseudomonas and Xanthomonas, bacteria of the family Enterobacteriaceae, in particular the genera Escherichia, Klebsiella, Proteus, Providencia, Salmonella, Serratia and Shigella, bacteria of the family Pasteurellaceae, in particular the genus Haemophilus, bacteria of the family Micrococcaceae, in particular of the genera Micrococcus and Staphylococcus, bacteria of the Streptococceae family, in particular of the genera Streptococcus and Enterococcus and bacteria of the Bacillaceae family, in particular of the genera Bacillus and Clostridium, and in d he Helicobacter eradication therapy for ulcers of the gastrointestinal tract.

Use according to claim 6 for the treatment of infections caused by viruses selected from the group consisting of viruses of the genus Parvoviridae, in particular parvoviruses, dependoviruses, densoviruses, viruses of the genus Adenoviridae, in particular adenoviruses, mastadenoviruses, aviadenoviruses, Viruses of the genus Papovaviridae, in particular papovaviruses, in particular papillomaviruses (so-called wart viruses), polyomaviruses, in particular JC virus, BK virus, and miopapovaviruses, viruses of the genus Herpesviridae, in particular herpes simplex virus, of the varicella / Zoster viruses, human cytomegalovirus, Epstein-Barr viruses, human herpes virus 6, human herpes virus 7, human herpes virus 8, viruses of the genus Poxviridae, especially smallpox viruses, Orthopox- Parapox-, Molluscum-Contagiosum- Virus, aviviruses, capriviruses, leporipox viruses, primarily hepatotropic viruses, especially hepatitis viruses, such as hepatitis A viruses, hepatitis B viruses, hepatitis C viruses, hepatitis D viruses, hepatitis E viruses, hepatitis F viruses Viruses, hepatits G viruses, hepadnaviruses, in particular all hepatitis viruses, such as hepatitis B virus, hepatitis D viruses, viruses of the Picornaviridae genus, in particular Picornaviruses, all enteroviruses, all polioviruses, all

Coxsackieviruses, all echoviruses, all rhinoviruses, hepatitis A virus, aphthoviruses, viruses of the genus Calciviridae, in particular hepatitis E viruses, viruses of the genus Reoviridae, in particular reoviruses, orbiviruses, rotaviruses, viruses of the genus Togaviren, in particular Togaviridae Alphaviruses, rubiviruses, pestiviruses, rubella virus, viruses of the genus Flaviviridae, in particular flaviviruses, TBE virus, hepatitis C virus, viruses of the

Genus Orthomyxoviridae, in particular influenza viruses, viruses of the genus Paramyxoviridae, in particular Paramyxoviruses, morbillivirus, pneumovirus, measles virus, mumps virus, viruses of the genus Rhabdoviridae, in particular Rhabdoviruses, Rabiesvirus, Styrenon virus virus, virus virus, virus virus, virus virus, virus virus, virus virus, virus virus, virus virus, virus virus, virus virus, virus virus virus, viscous virus virus Viruses of the genus Bunyaviridae, in particular Bunyaviruses, Nairovirus, phlebovirus, uukuvirus, Hantavirus, Hantaan virus, viruses of the genus Arenaviridae, in particular Arena viruses, lymphocytic choriomeningitis virus, viruses of the genus Retroviridae, in particular human T-cell leukemia virus, oncornaviruses, spuma viruses, lentiviruses, all HI viruses, viruses of the Filoviridae genus, in particular Marburg and Ebola viruses, slow viruses, prions, oncoviruses and leukemia viruses.

9. Use according to claim 6 for the prevention and treatment of infections caused by unicellular parasites, namely pathogens of malaria, sleeping sickness, Chagas disease, toxoplasmosis, amoebic dysentery, and leishmaniasis

Trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcomocystosis, Akantha-Möbose, Naeglerose, coccidiosis, giardiosis and lambliosis.

10. Use according to one of claims 1 to 9 in a pharmaceutical preparation, characterized in that the pharmaceutical preparation has an effective content of at least one organophosphorus compound according to one of claims 1 to 5 together with a pharmaceutically acceptable carrier.

11. Use according to claim 10, characterized in that the pharmaceutical preparation contains at least one further pharmaceutical active ingredient.

12. Use according to one of claims 10 or 11, characterized in that the pharmaceutical preparation comprises one or more constituents of the group consisting of sulfo- namid, sulfadoxin, artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, praziquantil, niclosamide, mebendazole, pyrantel, mifloinazonifone, pyrantel, tiabendazonazine, Oxamniquin, Bithionol and Suramin exist.

13. Use according to one of claims 1 1 to 12, characterized in that the pharmaceutical preparation comprises one or more constituents from the group consisting of penicillin, benzylpenicillin (penicillin G), phenoxypenicillin, isoxazolylpenicillin, aminopenicillin, ampicillin, amoxixillin, bacampicillin, Carboxypenicillin, Ticarcillin, Temocillin, Acyalaminopenicilline, Azlocillin, Mezlocillin, Piperacillin, Apalcillin, Mecillinam, Cephalosporine, Cefazolin Group, Cefuroxim Group, Cefoxitin Group, Cefoxetefoxoxinin, Cefotoxefanoxoxinin, Cefotoxefinoxoxinin, Cefotoxefinoxoxinin, Cefotoxefinoxoxinin, Cefotoxefinoxoxinin, Cefotoxefinoxoxininoxoxininoxoxininoxoxinoxoxinin group Cefozidim, ceftazidime group, ceftazidime, cefpirome, cefepime, other cephalosporins, Cefsulo- din, cefoperazone, Oralcephalosporine the cephalexin group, loracarbef, cefprozil, new Oralcephalosporinen extended spectrum, cefixime, cefpodoxime proxetil, cefuroxime axetil, cefetamet , Cefotiam-hexetil, cefdinir, ceftibutene, other ß-lactam antibiotics, carbapenem, imipenem / cilastatin, meropenem, biapenem, Aztreonam, ß-lactamase inhibitor, clavulanic acid / amoxicillin, clavulanic acid / ticarcillin, sulbacarne / ampicillin, tazobactam / piperacillin, tetracycline, oxytetracycline, rolitetraxyxlin,

Doxycycline, xithromycin minocycline, chloramphenicol, aminoglycosides, gentamicin, tobramycin, netilmicin, amikacin, Spectinomyxin, macrolides, erythromycin, clarithromycin, Ro, azithromycin, dirithromycin, spiramycin, josamycin, lincosamides, clindamycin, fusidic acid, glycopeptide antibiotics, vancomycin, Tecoplanin, Pristaminomycin derivatives, fosfomycin, antimicrobial folic acid antagonists, sulfonamides,

Co-trimoxazole, trimethoprim, other diaminopyrimidine-sulfonamide combinations, nitrofurans, nitrofurantoin, nitrofurazone, gyrase inhibitors (quinolones), norfloxacin, ciprofloxacin, ofloxacin, sparfloxacin, enoxacin, fleroxacinimidolimidominoximine, lefloxacoxin, pef Medium, isoniazid, rifampicin, rifabutin, ethambutol, pyrazinamide, streptomycin, capreomycin, prothionamide, terizidon, dapson, clofazimin, local antibiotics, bacitracin, tyrothricin, polymyxine, neomycin, kanamycin, parominomycine, antiririr, mir , Azidothymidine, didanosine, zalcitabine, thiacytidine, stavudine, ribavirin, idoxuridine, trifluridine, foscarnet, amantadine, interferons, tibol derivatives, proteinase inhibitors, antifungals, polyenes, amphothericin B, nystole, natamycin, azamycin

Azoles for septic therapy, miconazole, ketoconazole, itraconazole, fluconazole, UK-109,496, azoles for topical application, clotrimazole, econazole, isoconazole, oxiconazole, bifonazole, flucytosine, griseofulvin, ciclopiroxolamine, tolnaftate, naftifine, terbinafine, amorolfine, anthraquinones, Betulinic acid , Semianthraquinones, xanthones, naphtoquino ne, aryamino alcohols, quinine, quinidines, mefloquine, halofantrine, chloroquine, amodiaquine, acridine, benzonaphthyridine, mepacrine, pyronaridine, dapsone, sulfonamides, sulfadoxine, sulfalene, trimethoprim, proguanil, chlorproguanil, diaminopethinoquinoline, pyraminarimine, diaminopyrinoquinoline, pyraminarimine, pyraminimine, pyraminimine, 23, aminopyrimine, prinimine, aminopyrimine , tetracycline, doxycycline, clindamycin, norfloxacin, ciprofloxacin, ofloxacin, artemisinin, dihydroartemisinin, 1 Whether artemether, arteether, artesunate, atovaquone, suramin, melarsoprol, Nifürtmox, stibogluconate-sodium, pentamidine, amphotericin B, metronidazole, clioquinol, mebendazole, niclosamide, Praziquantel, pyrantel, tiabendazole, diethylcarbamazine, ivermectin, bithionol, oxamniquin, metrifonate, piperazine, embonate.