WO2001060829A1 - Phosphororganic compounds and the use thereof - Google Patents

Abstract

The invention concerns the use of phosphororganic compounds of general formula (I), wherein A represents propylene, 2-oxopropylene or 3-oxopropylene. The invention also concerns the use of said compounds for therapeutic and prophylactic treatment of infections in humans and animals caused by virus, bacteria, fungi and parasites and to their use as fungicides, bactericides and herbicides.

Description

 Organophosphorus compounds and their use

The invention relates to organophosphorus compounds and their salts. Esters and amides and their use in the therapeutic and prophylactic treatment of infections in humans and animals caused by viruses, bacteria, fungi and parasites and their use as fungicides, bactericides and herbicides in plants. According to the invention, the organophosphorus compounds comprise 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 not only have a potent activity, but also, in contrast to other medicinal products or crop protection agents, have reduced side effects or cause less environmental pollution and this means a lower health risk for humans.

The object of the present invention is therefore to provide a substance that is universal in infections by viruses, bacteria. Fungi and parasites can be used in humans and animals and as a fungicide, bactericide and herbicide in plants and fulfills the conditions specified above.

This object is achieved in a completely surprising manner by the group of substances defined in claim 1. This group of substances shows both an anti-infectious effect against viruses. Bacteria. Fungi, single and multicellular parasites as well as a fungicidal, bactericidal and herbicidal effect on plants.

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

in which A is propylene, 2-oxopropylene or 3-oxopropylene, in which R- is selected from the group. those of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, and substituted unsubstitu- ized heterocyclic radical. Halogen and OX- exists. wherein Xi are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted Hydroxvalkvl, substituted and unsubstituted alkenyl. substituted and unsubstituted alkynyl, substituted and unsubstituted aryl, substituted and unsubstituted acyl. substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical and in which R ₂ and R _{3 are the} same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl. substituted and unsubstituted hydroxvalkvl, substituted and unsubstituted aryl, substituted and unsubstituted acyl. substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl. substituted and unsubstituted cycloalkyl. substituted and unsubstituted heterocyclic radical. Halogen. OX ₂ or OX ₃ exists. wherein X or X may be the same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxylalkyl. substituted and unsubstituted aryl, substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted cycloalkyl, substituted 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 pharmaceutically acceptable salts. Esters and amides and salts of the esters.

R is preferably selected from the group consisting of a hydrogen radical, a methyl radical, an ethyl radical and a phenyl radical.

Furthermore, R ₂ and R ₃ are preferably identical or different and selected from the group consisting of a methyl radical, an ethyl radical, OX ₂ and OX ₃ , X and X _{3 being} particularly preferably selected from the group consisting of sodium, a Methyl group, an ethyl group and a phenyl group.

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, carbonic acid, carbamic acid or the thioic acid or imidic acid corresponding to the individual acids above, or from an organic sulfonic acid, these acids each Weil include aliphatic, aromatic and / or heterocyclic groups in the molecule as well as carbamoyl or carbamimidoyl.

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.);

Alkyl carbamimidoyl (e.g. methyl carbamimidoyl 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 (e.g. fluorine, chlorine, bromine etc.), hydroxy, hydroxyimino. 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 e.g. with amino. Carboxy, amino and carboxy, halogen. To name acylamino or the like substituted alkanoyle.

Aromatic acyl radicals are those acyl radicals which originate from an acid with a substituted or unsubstituted aryl group, where the aryl group can include phenyl, toluyl, xylyl, naphthyl and the like; suitable examples are given below:

Aroyl (e.g. benzoyl, toluoyl. Xyloyl, naphthoyl. Phthaloyl etc.);

Aralkanoyl (e.g. phenylacetyl etc.); Aralkenoyl (e.g. cinnamoyl etc.);

Aryloxyalkanoyl (e.g. phenoxyacetyl etc.);

Arylthioalkanoyl (e.g. phenylthioacetyl etc.);

Arylaminoalkanoyl (e.g. N-phenylglycyl, etc.);

Arenesulfonyl (e.g. benzenesulfonyl, tosyl or toluenesulfonyl, naphthalenesulfonyl etc.); Aryloxycarbonyl (e.g. phenoxycarbonyl, naphthyloxycarbonyl etc.); Aralkoxycarbonyl (e.g. benzyloxycarbonyl etc.); Arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.); Arylglyoxyloyl (e.g. phenylglyoxyloyl etc.). 5

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 already started

10 were given. 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 with hydroxy, hydroxyimino. Dihaloalkanoyloxyimino substituted aralkanoyl and arylthiocarbamoyl (e.g. phenylthiocarbamoyl etc.);

15 arylcarbamimidoyl (e.g. phenylcarbamimidoyl etc.).

A heterocyclic acyl radical is understood to mean an acyl radical which comes from an acid with a heterocyclic group; this includes:

20 Heterocyclic carbonyl, in which the heterocyclic radical is an aromatic or aliphatic 5 to 6-membered heterocycle with at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (e.g. thiophenyl, furoyl, pyrrole carbonyl, nicotinoyl etc.);

Heterocycle alkanoyl, in which the heterocyclic radical is 5- to 6-membered and at least 25 has a heteroatom from the group consisting of nitrogen, oxygen and sulfur (for example thiophenyl-acetyl, furylacetyl, imidazolylpropionyl. Tetrazolylacetyl, 2- (2-amino- 4-thiazolyl) -2-methoxyiminoacetyl etc.) and the like.

In the above examples of heterocyclic acyl groups, the heterocycle and / or the aliphatic hydrocarbon portion may optionally have one or more suitable substituents, such as the same ones that have been stated to be suitable for alkyl and alkane groups.

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

_. 5

"Hydroxylalkyl" is a straight or branched chain alkyl radical with up to 26 carbons, which has at least one hydroxyl group, preferably one or two hydroxyl groups.

"Alkenyl" includes straight or branched chain alkenyl groups with up to 26 carbon atoms. Substance atoms, such as vinyl. Propenyl (e.g. 1-propenyl, 2-propenyl), 1-methyl propenyl, 2-methyl propenyl, butenyl. 2-Ethylpropenyl. Pentenyl, hexenyl.

"Alkynyl" includes straight or branched chain alkynyl groups with up to 26 carbon atoms.

Cycloalkyl preferably represents an optionally substituted C _3-7 cycloalkyl; possible substituents include alkyl. Alkenyl. Alkynyl. Alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. fluorine, chlorine, bromine etc.). Nitro and the like are suitable.

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

"Aralkyl" includes mono-, di-, triphenylalkyls such as benzyl, phenethyl, benzhydryl. Tritvl and the like, where the aromatic part may have one or more suitable substituents such as alkoxy (e.g. methoxy, ethoxy etc.), halogen (e.g. Fluorine, chlorine, bromine, etc.), nitro and the like.

The radicals X and X ₃ can also be chosen so that esters are formed on the phosphono group or phosphino group. Suitable examples of such esters according to the formula (I) include generally suitable mono- and diesters, for example alkyl esters (for example methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, hexyl ester, etc.); Aralkyl esters (benzyl esters, phenethyl esters, benzhydryl esters, trityl esters, etc.); Aryl esters (for example phenyl esters, tolyl esters, naphthyl esters, etc.); Aroyl alkyl esters (eg phenacyl esters etc.); and silyl esters (e.g. 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.

As described above, methyl, ethyl and phenyl esters are particularly preferred.

Furthermore, X ₂ and X _{3 can be} a metal of the first, second or third main group of the periodic table, ammonium, substituted ammonium, or ammonium compounds derived from ethylenediamine or amino acids. That is, the salt compounds of the organophosphorus compounds with organic or inorganic bases (for example sodium salt, potassium salt, calcium salt, aluminum salt, ammonium salt, magnesium salt, trie thylamine salt, ethanolamine salt. Dicyclohexylamine. Ethylenediamine salt, N, N'-dibenzylethylenediamine salt etc.) and salts with amino acids (for example arginine acid, aspartic acid salt, glutamic acid salt etc.) and the like are formed. The sodium salt is preferred.

The compounds according to the formula (I) according to the invention can, however, in their protonated form as ammonium salt of organic or inorganic acids, such as hydrochloric acid. Hydrobromic. Sulfuric acid. Nitric acid. Methane sulfonic acid. p-toluenesulfonic acid. Acetic acid. Lactic acid. Maleic acid. Fumaric acid. Oxalic acid. Tartaric acid. Benzoic acid. etc. are available.

The compounds of formula (I) according to the invention allow spatial isomers to occur for double or chiral groups R 1, R ₂ , R ₃ , Xi, X2, 3 or A. The use of the compounds according to the invention includes all spatial isomers both as pure substances and in the form of their mixtures.

The preferred compounds are listed below:

N-Hydroxy-4-phosphonobutyric acid amide monosodium salt

N-Hydroxy-N-methyl-4-phosphonobutyric acid amide monosodium salt

N-Hydroxy-N-phenyl-4-phosphonobutyric acid amide monosodium salt

N-hydroxy-N-

(2-hydroxyethyl) -

mononatriumsalz N-( 1 -Carboxypropyl)-4-phosphonobutyric acid amide

monosodium salt N- (1-carboxypropyl) -

N-hydroxy-4-phosphonobutyric acid amide monosodium salt

N-hydroxy-N-

(4-imidazolyl) -4-phosphonobutyric acid amide monosodium salt

N-ethyl-N-hydroxy-4-ethylphosphonobutyric acid amide monosodium salt

N-Benzyl-N-hydroxy-4-ethylphosphonobutyric acid amide monosodium salt

N-allyl-N-hydroxy-4-ethylphosphonobutyric acid amide monosodium salt

N-Hydroxy-N- (3- (3-phenylpropionyl) -4-ethylphosphonobutyric acid amide monosodium salt

N- (4-fluorobenzyl) -N-hydroxy-4-ethylphosphonobutyric acid amide monosodium salt

N-hydroxy-N-n-propyl-

N-Hydroxy-N- ortho-tolyl-4-diethyl- phosphonobuttersäureamid4-diethylphosphonobutyric acid amide

N-hydroxy-N-ortho-tolyl-4-diethyl-phosphonobutyric acid amide

N-but-3-ynyl-N-hydroxy

4-diethylphosphonobutyric acid amide

N- (1-Carboxy-2-methyl-propyl) -N-hydroxy-4-diethylphosphonobutyric acid amide

N-Hydroxy-N- (2 - (4-hydroxyindol-3-yl) ethyl) -4-diethylphosphonobutyric acid amide

N-hydroxy-N-isopropyl-4-dimethyl-phosphine-oxo-butyric acid amide

N- «etα-ethylbenzyl-N-hydroxy-4-dimethyl-phosphineoxido-butyric acid amide

N-Cyclohex-2-enyl-N-hydroxy-4-dimethyl-phosphineoxido-butyric acid amide

N-Carbamoyl-N-hydroxy- 4-dimethylphosphinoxido- buttersäureamidN- (1-Carboxy-2-methylbutyl) -N-hydroxy-4-dimethylphosphineoxido-butyric acid amide

N-carbamoyl-N-hydroxy-4-dimethylphosphineoxido-butyric acid amide

N - "- Butyl-N-hydroxy-4- (P-methylphosphinato) butyric acid amide

N-Hydroxy-N- (pαrα-isopropylbenzyl) -4- (P-methyl-phosphinato) butyric acid amide

N-Hydroxy-N- (4,4,4-trifluorobutyl) -4- (P-methylphosphinato) butyric acid amide

N-carboxymethyl-N-hydroxy-4- (P-methylphosphinato) butyric acid amide

N-ethoxycarbonyl-N-hydroxy-4- (P-methylphosphinato) butyric acid amide

natriumsalzN-isobutyl-N-hydroxy-4-oxo-4-phosphonobutyric acid amide mono-

sodium salt

N-Cyclohexyl-N-hydroxy- 4-oxo-4-phosphono- buttersäureamidmono- natriumsalzN-ortΛo-chlorophenyl-N-hydroxy-4-oxo-4-phosphonobutyric acid amide sodium salt

N-Cyclohexyl-N-hydroxy-4-oxo-4-phosphonobutyric acid amide monosodium salt

N- (l-carboxyethyl) - N-hydroxy-4-oxo-4-phosphonobutyric acid amide monosodium salt

N-Hydroxy-N- (2- (N-hydroxycarbamoyl) ethyl) -4-oxo-4-phosphonobutyric acid amide monosodium salt

N-tert-butyl-N-hydroxy-4-ethylphosphono-4-oxo-butyric acid amide monosodium salt

N-pαra-nitrophenyl-N-hydroxy-4-ethyl-phosphono-4-oxo-butanoic acid monosodium salt

N- (4-oxocyclohexyl) -N-hydroxy-4-ethyl-phosphono-4-oxo-butyric acid amide monosodium salt

N- (1-carboxy-1-methyl-ethyl) -N-hydroxy-4-ethyl-phosphono-4-oxo-butyric acid amide monosodium salt

N-Hydroxy-N-«- pentyl-4-diethyl- phosphono-4-oxo- buttersäureamidN- (3-Chloro-2_2-dimethylpropyl) - N-hydroxy-4-ethylphosphono -4-oxo-butanoic acid monosodium salt

N-Hydroxy-N - «- pentyl-4-diethyl-phosphono-4-oxobutyric acid amide

N-Hydroxy-N- (3-acetyl-4-methoxy-phenyl) -4-diethyl-phosphono-4-oxo-butyric acid amide

N-Hydroxy-N- (3-methyicyclohexyl) 4-diethylphosphono-4-oxo-butyric acid amide

N- (5-Amino-1-carboxy-pentyl) -N-hydroxy-4-diethyl-phosphono-4-oxo-butyric acid amide

N-Hydroxy-N- (3- (N-morpholino) propyl) -4-diethyl-phosphono-4-oxo-butyric acid amide

buttersäureamidN-hydroxy-N-isobutyl-4-dimethyl-phosphono-4-oxo

butyric

N-betα-naphthyl-N-hydroxy-4-dimethyl-phosphinoxido-4-oxobutyric acid amide

N-( 1 -Carboxy-3-methyl- butyl)-N-hydroxy-4- dimethyl-phosphinoxido- 4-oxo-buttersäureamid

N- (4-hydroxymethyl-2-phenyl-1,3-dioxan-4-yl) -N-hydroxy-4-dimethylphosphine-oxo-4-oxo-butyric acid amide

N- (1-carboxy-3-methyl-butyl) -N-hydroxy-4-dimethyl-phosphine-oxo-4-oxo-butyric acid amide

N- (2-furyl) -N-hydroxy-

4-dimethylphosphinoxido-4-oxo-butyric acid amide

N- (3-methylpentyl) - N-hydroxy-4- (P-methylphosphinato) -4-oxobutyric acid amide

N-Hydroxy-N - (/ «etα-pyridyl) -4- (P-methyl-phosphinato) -4-oxobutyric acid amide

N-Hydroxy-N- (1-cyano-cyclohexyl) -4- (P-methyl-phosphinato) -4-oxo-butyric acid amide

buttersäureamidN- (1-carboxypentyl) - N-hydroxy-4- (P-methylphosphinato) -4-oxo-

butyric

N- (N-phenylcarbamoyl) - N-hydroxy-4- (P-methylphosphinato) -4-oxobutyric acid amide

i j -N-Hydroxy-NH-octyl-3-oxo-4-phosphono-butter-acid amide monosodium salt

ij -

N-Hydroxy-N- (2-indolyl) -3-oxo-4-phosphonobutter acid amide monosodium salt

ONa

OlH JU

mononatriumsalzN-hydroxy-N-dec-9-enyl 3-oxo-4-phosphonobutyric acid amide-

monosodium salt

N- (1-Carboxy-3-methyl-thio-propyl) -N-hydroxy-3-oxo-4-phosphonobutyric acid amide monosodium salt

N-Hydroxy-N- (2,2.2-trichloroethyl) -3-oxo-4-phosphonobutyric acid amide monosodium salt

N-decyl-N-hydroxy-3-oxo-4-ethylphosphonobutyric acid amide monosodium salt

N- (2-Fluorenyl) -N-hydroxy-3-oxo-4-ethyl-phosphono-butyric acid amide monosodium salt

N- (l-Adamantyl) - N-hydroxy-3-oxo-4-ethyl-phosphono-butyric acid amide monosodium salt

N-(N-(2,4-Dimethyl-phenyl)- carbamoyl)-N-hydroxy-3-oxo- 4-ethylphosphono-buttersäure- amidmononatriumsalzN- (1,4-dioxan-2-yl) - N-hydroxy-3-oxo-4-ethylphosphonobutyric acid amide monosodium salt

N- (N- (2,4-Dimethylphenyl) carbamoyl) -N-hydroxy-3-oxo-4-ethylphosphonobutyric acid amide monosodium salt

N- (3-Methyl-hex-2-yl) - N-hydroxy-3-oxo-4-diethylphosphonobutyric acid amide

N-metα-tolyl-N-hydroxy-3-oxo-4-diethyiphosphonobutyric acid amide

N- (3-Acetylaminopropyl) - N-hydroxy-3-oxo-4-diethylphosphonobutyric acid amide

N- (2-Pyrroiidon-5-yl) - N-hydroxy-3-oxo-4-diethylphosphonobutyric acid amide

N- (2- (Methylsulfoxido) ethyl) -N-hydroxy-3-oxo-4-diethylphosphonobutyric acid amide

N-dodecyl-N-hydroxy-3-oxo-4-dimethylphosphineoxidobutyric acid amide

- 13 -N-pαrα-hydroxyphenyl-N-hydroxy-3-oxo-4-dimethylphosphineoxido-butyric acid amide

- 13 -

N- (2-propionylethyl) - N-hydroxy-3-oxo-4-dimethylphosphineoxido-butyric acid amide

N- (l-Carboxy-2- (3,4-dihydroxyphenyl) ethyl) - N-hydroxy-3-oxo-4-dimethylphosphineoxido-butyric acid amide

N- (3 -phosphonopropyl) - N-hydroxy-3-oxo-4-dimethylphosphineoxido-butyric acid amide monosodium salt

N- (3-ethyl-4-methylpentyl) - N-hydroxy-3-oxo-4- (P-methylphosphinato) butyric acid amide

N- (3-Hydroxy-3-phenyl-propyl) -N-hydroxy-3-oxo 4- (P-methyl-phosphinato) butyric acid amide

N- (2- (2-methoxy-ethoxy) ethyl) -N-hydroxy-3-oxo-4- (P-methyl-phosphinato) butyric acid amide

N- (4-Imidazolyl-methyl) - N-hydroxy-3-oxo-4- (P-methyl-phosphinato) - butyric acid amide

N- (2- (7- (2- (N, N-Diethylamino) ethoxy) fluoren-9-one-2-yloxy) ethyl) -N-hydroxy-3-oxo-4- (P-methyl -phosphinato) -buttersäureamid.

Further preferred compounds are listed in the examples.

The compounds N-hydroxy-4-phosphonobutyric acid amide monosodium salt and N-hydroxy-N-yl-4-phosphonobutyric acid amide monosodium salt are particularly preferred.

The organophosphorus compounds are particularly suitable for the therapeutic and prophylactic treatment of infections in humans and animals caused by viruses. Bacteria, single and multicellular parasites and fungi are caused. According to the invention, unicellular parasites are only to be understood as protozoa in accordance with the narrow definition of parasitology.

The compounds are active against unicellular parasites (protozoa), in particular against pathogens of malaria and sleeping sickness as well as Chagas disease, toxoplasmosis. the amoebic dysentery, the leishmaniasis. trichomoniasis. pneumocystosis. the Balantiosis. cryptosporidiosis. Sarcocystosis. the Akanthamöbose. the nail rose. coccidiosis. Giardiosis and Lambliosis.

They are therefore particularly useful as malaria prophylaxis and as a prophylaxis of sleeping sickness and Chagas disease. toxoplasmosis. amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis. balantidiosis, cryptosporidiosis, sarcocystosis. the Akanthamöbose. the nail rose. coccidiosis. Giardiosis and Lambliosis.

The active compounds according to the invention can be used in particular against the following bacteria:

Bacteria of the Propionibacteriaceae family. especially the genus Propionibacterium, especially the species Propionibacterium acnes; Bacteria of the Actinomycetaceae family, in particular of the Actinomyces genus; Bacteria of the genus Corynebacterium, in particular the species Corynebacterium diphteriae and Corynebacterium pseudotuberculosis; Bacteria of the family Mycobacteriaceae, of the genus Mycobacterium, in particular the species Mycobacterium leprae, Mycobacterium tuberculosis. Mycobacterium bovis and Mycobacterium avi- around; 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, of the species Yersinia pestis. Yersinia pseudotuberculosis, Yersinia enterocolitica and Yersinia ruckeri; Bacteria of the Mycoplasmataceae family. the genera Mycoplasma and Ureaplasma, especially the species Mycoplasma pneumoniae; Bacteria of the genus Brucella; Bacteria of the genus Bordetella; Bacteria of the family Neiseriaceae. especially the genera Neisseria and Moraxella. especially the species Neiseria meningitides. Neisseria gonorrhoeae and Moraxella bovis; Bacteria of the Vibrionaceae family. especially the genera Vibrio, Aeromonas. Plesiomonas and Photobacterium. especially the Vibrio cholerae species. Vibrio anguillarum and Aeromonas salmonici- das: bacteria of the genus Campylobacter, especially the species Campylobacter jejuni. Campylobacter coli and Campylobacter fetus; Bacteria of the genus Helicobacter, in particular the species Helicobacter pylori: bacteria of the Spirochaetaceae and Leptospiraceae families, in particular of the Treponema genus. Borrelia and Leptospira, especially Borrelia burgdorferi; Bacteria of the genus Actinobacillus; Bacteria of the Legionellaceae family. the genus Legionella; Bacteria of the Rickettsiaceae family and Bartonellaceae family: bacteria of the genera Nocardia and Rhodococcus; Bacteria of the genus Dermatophilus bacteria of the family Pseudomonadaceae, in particular of the genera Pseudomonas and Xanthomonas; Bacteria of the Enterobacteriaceae family, especially of the Escherichia genera. Klebsieila, Proteus. Providencia, Salmonella. Serratia and Shigella; Bacteria of the Pasteurellaceae family, especially of the genus Haemophilus; Bacteria of the Micrococcaeeae family, in particular the genera Micrococcus and Staphylococcus; Bacteria of the Streptococcaceae family. especially the genera Streptococcus and Enterococcus and bacteria of the family Bacillaceae, especially the genera Bacillus and Clostridium.

Organophosphorus compounds and their derivatives are therefore suitable for the treatment of diphtheria. Acne vulgaris, listeriosis, erysipelas in animals, gas burns in humans and animals, para-burns in humans and animals, tuberculosis in humans and animals, leprosy, and other mycobacteriosis in humans and animals, paratuberculosis in animals, plague, mesenteric Lymphadenitis and pseudotuberculosis in humans and animals, cholera, legionnaires' disease, Lyme disease in humans and animals, leptospirosis in humans and animals. Syphilis, Campylobacter enteritis in humans and animals, Moraxella keratoconjunctivitis and serositis in animals, brucellosis in animals and humans, anthrax in humans and animals, actinomycosis in humans and animals, streptotrichoses, psittacosis / ornithosis in animals, Q fever, Ehrlichiosis ,

It is also useful in Helicobacter eradication therapy for ulcers of the brain. gendarme tract.

A combination with another antibiotic can also be used to treat the above-mentioned diseases. Isoniazid, rifampicin are particularly suitable for combination preparations with other anti-infectives. Ethambutol, pyrazinamide. Streptomycin, protionamide and dapsone for the treatment of tuberculosis.

The active compounds according to the invention can also be used in particular for infections with the following viruses: Parvoviridae: Parvoviruses, Dependoviruses. Denso viruses; Adenoviridae: adenoviruses. Mastadeviruses, aviadenoviruses: Papovaviridae: Papovaviruses, in particular papillomaviruses (so-called wart viruses), polyomaviruses. especially JC virus. BK virus, and miopapovavirus; Herpesviridae: All herpes viruses, especially herpes simplex viruses. of the varicella / zoster viruses. human cytomegalovirus, Epstein-Barr virus, all human herpes viruses. human herpes virus 6, human herpes virus 7, human herpes virus 8; Poxviridae: smallpox, 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 G viruses; Hepadnaviruses: all hepatitis viruses. Hepatitis B virus, hepatitis D virus; Picornaviridae: Picornaviruses, all enteroviruses, all polioviruses, all Coxsackieviruses. all echoviruses, all rhinoviruses, hepatitis A virus, aphthoviruses; Calciviridae: hepatitis E viruses; Reoviridae: Reoviruses. Orbiviruses, rotaviruses; Togaviridae: Togaviruses, Alphaviruses,, Rubiviruses, Persiviruses. rubella; Flaviviridae: Flaviviruses, TBE virus. Hepatitis C virus; Orthomyxoviridae: all influenza viruses; Paramyxoviridae: Paramyxoviruses. Morbillivirus. Pneumovirus, measles virus. Mumps virus; Rhabdoviridae: rhabdoviruses, rabies virus, lyssavirus, viscous stomatitis virus; Coronaviridae: Coronaviruses; Bunyaviridae: Bunyaviren. Nairovirus, phlebo virus, uukuvirus, hantavirus; Arenaviridae: Arenaviruses, lymphocytic choriomeningitis virus; Retroviridae: retroviruses. all HTL viruses, human T-cell leukemia virus, oncornaviruses. Spumaviruses, lentiviruses, all HI viruses; Filoviridae: Marburg and Ebola viruses; Slow virus infections. prions; Oncoviruses. 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 of tumors of the genital organs caused by papillomaviruses in humans, eradication of JC viruses and BK viruses, eradication of herpes viruses, eradication of human herpes viruses 8 for the treatment of Kaposi's sarcoma, eradication of cytomegaloviruses Transplants, eradication of Eppstein-Barr viruses before transplantation and for the prevention of Eppstein-Barr virus-associated tumors, eradication of hepatitis viruses for treatment of chronic liver diseases and for the prevention of liver tumors and cirrhosis. Eradication of coxsackieviruses in cardiomyopathies, eradication of 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 organs (keratoconjunctivitis), the nervous system (poliomyelitis, meningoencephalitis, encephalitis, subacute sclerosing panencephalitis, SSPE, progressive multifocal leukoencephalopathy, lymphocytic choriomeningitis (gastrointestinalitis), , Gastroenteritis, diarrheal diseases), the liver and the biliary system (hepatitis, cholangitis, hepatocellular carcinoma), the lymphoid tissue (mononucleosis, lymphadenitis), the hematopoietic system, the genital organs (mumps orchestral disease), the skin (warts. matitis, herpes labialis. Cold sores. Herpes zoster. Shingles), the mucous membranes (papillomas, conjunctive apapillomas, hyperplasias, dysplasias), the cardiovascular system (arteritis, myocarditis, endocarditis, pericarditis), the kidney-hamway system. of the genital organs (anogenital lesions. warts. genital warts, pointed condylomas. dysplasias, papillomas. cervical dysplasias. condylomata acuminata, epidermodysplasia verruciformis), the organs of movement (myositis. myalgias), treatment of foot-and-mouth disease of the cloven hoofed pox. of dengue syndrome, hemorrhagic fever. early summer meningoencephalitis (TBE) and yellow fever.

The connections described, i.e. the organophosphorus compounds of the formula (I), and esters and amides thereof on the phosphono- or phosphino group and salts thereof show a strong cytotoxic activity against single- and multicellular parasites. especially against the pathogens of malaria and sleeping sickness. Accordingly, the compounds of the invention are useful for the treatment of infectious diseases caused by viruses. Bacteria, parasites and fungi are caused in humans and animals. The compounds are also suitable for use in preventing diseases caused by viruses, bacteria, parasites and fungi, in particular as malaria prophylaxis and as sleeping sickness prophylaxis.

The organophosphorus compounds according to the invention, these generally include pharmaceutically acceptable salts, amides. Esters, a salt of such an ester, or compounds which, when applied, provide the compounds according to the invention as metabolites or degradation products, also called "prodrugs", can be administered for administration in any suitable manner analogously to known anti-infectious agents (mixed with a non-toxic pharmaceutically acceptable carrier). Pharmaceutically acceptable salts of the compounds include salts which the compounds of the formula according to the invention in their protonated form as the ammonium salt of inorganic or organic acids, such as hydrochloric acid, sulfuric acid, citric acid, maleic acid. Fumaric acid, tartaric acid, p-toluenesulfonic acid. form.

The salts which are formed by suitable selection of X ₂ and X, such as sodium salt, are also particularly pharmaceutically suitable. 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 pharmaceutically active agents can be prepared in the form of pharmaceutical preparations in dosage units. This means that the preparation in the form of individual parts, e.g. B. tablets. Dragees. Capsules, pills, suppositories and ampoules are available, the active ingredient content of which corresponds to a fraction or a multiple of a single dose. The dosage units can e.g. B. 1. 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose. A single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.

Non-toxic, inert pharmaceutically suitable carriers are to be understood as solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all kinds.

Tablets and coated tablets are the preferred pharmaceutical preparations. Capsules, pills, granules. Suppositories, solutions. Suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays called. Tablets, coated tablets, capsules, pills and granules can contain the active ingredient (s) in addition to the usual carriers, such as (a) fillers and extenders, e.g. B. starches, milk sugar, cane sugar, glucose, mannitol and silica, (b) binders, e.g. B. 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 usual coatings and casings, optionally containing opacifying agents, and can also be composed such that they contain the active ingredient (s) only or preferably in a particular one Part of the intestinal tract may be released with a delay, with z. B. polymer substances and waxes can be used.

The active ingredient (s) can, if appropriate, also be present in microencapsulated form with one or more of the excipients specified above.

Suppositories can contain the usual water-soluble or water-insoluble excipients in addition to the active ingredient (s), e.g. B. polyethylene glycols, fats, e.g. B. cocoa fat and higher esters (z. B. C 14 alcohol with C16 fatty acid) or mixtures of these substances.

Anoint. Pastes, creams and gels can contain the usual excipients in addition to the active ingredient (s), e.g. B. animal and vegetable fats, waxes, paraffins, starch. Astragalus. Cellulose derivatives. Polyethylene glycols. Silicones, bentonites. Silicic acid, talc and zinc oxide or mixtures of these substances.

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. Glycerin, glycerin formal, tetrahydrofurfuryl alcohol. Contain polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances.

For parenteral administration, the solutions and emulsions can also be in sterile and blood-isotonic 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. Containing aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances.

The formulation forms mentioned can also be colorants. Preservatives as well as odor and taste-improved additives, e.g. B. peppermint oil and eucalyptus oil and Sweeteners, e.g. B. saccharin.

The active compounds of the formula (I) should be present in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5% by weight. preferably from about 0.5 to 95% by weight of the total mixture.

In addition to the compounds of the formula (I), the pharmaceutical preparations can also contain further active pharmaceutical ingredients.

Furthermore, the organophosphorus compounds in the pharmaceutical compositions in combination with sulfonamide, sulfadoxine. Artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine. Pyrimethamine, armesin. Tetracycline. Doxycycline, proguanil. Metronidazole, praziquantil. Niclosamide. Mebendazole, pyrantel. Tiabendazole, diethyl carbazine. Piperazine. Pyrivinum. Metrifonate. Oxamniquine. Bithionol or Suramin or more of these substances are present.

The pharmaceutical preparations listed above are prepared in a conventional manner by known methods, e.g. B. by mixing the active ingredient (s) with the carrier (s).

In humans and animals, the preparations mentioned can either be oral, rectal, parenteral (intravenous, intramuscular, subcutaneous), intracisternal. intravaginal, intraperitoneal, local (powder, ointment, drops) and for the treatment of infections in cavities. Body cavities can be applied. Injection solutions come as suitable preparations. Solutions and suspensions for oral therapy, gels. Pour-on formulations. Emulsions. Ointments or drops in question. For local therapy, ophthalmic and dermatological formulations can be used. 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 can also be used. Granules, pellets, tablets. Boli, capsules, aerosols,

Sprays, inhalants can 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, it has proven to be advantageous in both human and veterinary medicine to use the active ingredient (s) of the formula (I) in a total amount of from about 0.05 to about 600. preferably 0.5 to 200 mg kg of body weight per 24 Hours, if necessary in the form of several single doses, to achieve the desired results. A single dose contains the active ingredient (s) preferably in amounts of about 1 to about 200, especially 1 to 60 mg / kg body weight. 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 of the invention can be outstanding as bactericides. Fungicides and herbicides are used in plants. In particular, the compounds according to the invention are notable for good herbicidal activity. The invention accordingly also relates to a method for controlling unwanted plant life in crops of crops, the area in which they are cultivated being treated with an effective amount of a compound of the formula (I) according to the invention or of an agent comprising such a derivative.

The activity of the substances is determined in a test system. This system is based on the measurement of the inhibition of the growth of bacteria, parasites. Viruses. Mushrooms or plants in vitro. For this purpose, test methods are used which are known to the person skilled in the art. For example, the inhibition of malaria parasite growth in blood cultures is determined to determine antimalaria activity. The determination of the antibacterial activity is based on measuring the inhibition of bacterial growth on nutrient media and in liquid cultures. The determination of the antiviral activity is based on inhibition of the formation of viral elements in cell cultures. The determination of the fungicidal activity is based on the inhibition of the growth of fungi on nutrient media and in liquid cultures. 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.

In principle, the person skilled in the art knows which synthetic route he has to choose for the production of the substances according to the invention. Some synthetic routes for compounds of the invention are given below by way of example.

example 1

N-Hydroxy-4- (diethylphosphono) butyric acid amide (1 a 2.52 g (10 mmol) of 4-phosphonobutyric acid triethyl ester are dissolved in 20 ml of anhydrous methanol. A solution of 11 mmol of hydroxylamine in anhydrous methanol (filtered from 765 mg (11 mmol) Hydroxylamine hydrochloride and 253 mg (11 mmol) sodium in methanol) are added dropwise at 0 ° C. The resulting mixture is mixed with 10 mmol sodium methanolate (from 230 mg (10 mmol) sodium) in anhydrous mathanol at 0 ° C. It is added The mixture is filtered, the filter residue is taken up with a little water, HC1 is added until the reaction is weakly acid and the mixture is left to stand for a period of three weeks, giving N-hydroxy-4- (diethyl-phosphono) - butyric acid amide (la) as colorless crystals and in medium yield.

Example 2

N-Hydroxy-N-methyl-4- (diethylphosphono-butyric acid amide (2a) In Example 1, the procedure is similar, using N-methylhydroxylamine instead of hydroxylamine, and N-hydroxy-N-methyl-4- (diethylphosphono) butyric acid amide ( 2a) obtained as colorless crystals and in moderate yield.

Example 3

4-phosphono-N-hydroxybutyric acid amide (1 b)

3.06 g (20 mmol) of trimethylbromosilane are added dropwise to a solution of 1, 20 g (5 mmol) of N-hydroxy-4- (diethylphosphono) butyric acid amide (Ia) cooled to 0 ° C. in 50 ml of dry acetonitrile. It is stirred for 3 hours at room temperature. The solvent is then stripped off in vacuo and the residue is taken up in 20 ml of ice water. The mixture is stirred at room temperature for 1 hour and etherified twice with 20 ml of ether. A pH of 4.5 is set with 2 M NaOH. The water is then drawn off in a vacuum at a maximum of 50 ° C. The solid residue is crystallized from methanol / ethyl acetate. 4-Phosphono-N-hydroxybutyric acid amide (Ib) is obtained in the form of colorless microcrystals in low yield. Example 4

N-hydroxy-N-methyl-4-phosphonobutyric acid amide (2b)

The procedure corresponding to Example 3 is based on N-hydroxy-N-methyl-4- (diethylphosphono) butyric acid amide (2a) and N-hydroxy-N-methyl-4-phosphonobutyric acid amide (2b) in the form of colorless crystals and in medium yield receive.

Example 5

4- (diethylphosphono) -N-hvdroxyacetoacetic acid amide (3a) (or N-hvdroxy-3-oxo-4- (diethylphosphono-butyric acid amide) 2.78 g (10mmol) 4-diethylphosphonomethyl-2,2-dimethyl-l, 3-dioxen 4-one (prepared according to Org. Synth. Coll. Vol. VIII, 192-196) are placed in a pressure vessel, a solution of 11 mmol of hydroxylamine (filtered from 765 mg (11 mmol) of hydroxylamine hydrochloride and 253 mg (11 mmol) of sodium in methanol) in anhydrous methanol is added dropwise at 0 ° C. 10 mmol of sodium methoxide (from 230 mg (10 mmol) of sodium) in anhydrous methanol are added to the resulting mixture at 0 ° C. The vessel is closed and the mixture heated over a period of 2 hours to 60-70 ° C. After cooling, the precipitate formed is filtered off, the filter residue is taken up in a little water, HC1 is added to the weakly acidic reaction and left in the refrigerator overnight. (Diethylphosphono) -N-hydroxyacetoacetic acid amide (3 a) in Form of colorless crystals and obtained in moderate yield.

Example 6

4- (Diethylphosphono -N-hvdroxy-N-methylacetoacetic acid amide (4a) (or N-Hvdroxy-N-methyl-3-oxo-4- (diethylphosphono) -butyric acid amide according to Example 5, using N-methylhydroxylamine instead of hydroxylamine 4- (Diethylphosphono) -N-hydroxy-N-methylacetoacetic acid amide (4a) is obtained as colorless crystals and in moderate yield.

Example 7 N-Hvdroxy-4-phosphonoacetoacetic acid amide (3b) (or N-Hvdroxy-3-oxo-4-phosphono-butyric acid amide)

3.06 g (20 mmol) of trimethylbromosilane are added dropwise to a solution of 1.27 g (5 mmol) of 4- (diethylphosphono) -N-hydroxyacetoacetic acid amide (3a) in 50 ml of dry acetonitrile, cooled to 0 ° C. It is stirred for 3 hours at room temperature. The solvent is then stripped off in vacuo and the residue is taken up in 20 ml of ice water. The mixture is stirred at room temperature for 1 hour and etherified twice with 20 ml of ether. A pH of 4.5 is set with 2 M NaOH. The water is then drawn off in a vacuum at a maximum of 50 ° C. The solid residue is crystallized from methanol / ethyl acetate. N-hydroxy-4-phospho- Noacetoacetic acid amide (3b) obtained in the form of a colorless powder in good yield.

Example 8

N-Hvdroxy-N-methyl-4-phosphonoacetoacetic acid amide (4b) or (or N-Hvdroxy-N-methyl-3-oxo-4-phosphono-butyric acid amide

Following the procedure corresponding to Example 7, starting from 4- (diethylphosphono) - N-hydroxy-N-methylacetoacetic acid amide (4a), N-hydroxy-N-methyl-4-phosphonoacetoacetic acid amide (4b) is obtained in the form of colorless crystals and in medium yield.

The effects of various compounds according to the invention are given below in examples:

The following substances were examined: Substance 1: N-hydroxy-4-phosphonobutyric acid amide sodium salt Substance 2: N-Hydroxy-N-methyl-4-phosphonobutyric acid amide monosodium salt Substance 3: N-hydroxy-N-phenyl 4-phosphono-butyric acid amide monosodium salt substance 4: N-hydroxy-4- (P-memyl-phosphinato) -butyric acid amide monosodium salt substance 5: N-hydroxy-N-methyl-3-oxo-4- (P-methyl-phosphinato ) -butyric acid amide monosodium salt substance 6: N-hydroxy-3-oxo-4- (P-methyl l-phosphinato) -butyric acid amide monosodium salt substance 7: N-hydroxy-N-methyl-3-oxo-4-phosphono-butyric acid amide -monosodium salt substance 8: N-hydroxy-3-oxo-4-phosphono-butyric acid amide-monosodium salt substance 9: N-hydroxy-4-diphenylphosphono-butyric acid amide substance 10: N-hydroxy-N-phenyl-4-diphenylphosphono-butyric acid amide substance 11 : N-Hydroxy-N-benzyl-4-phosphono-butyric acid amide monosodium salt Substance 12: N-Hydroxy-N-benzyl-3-oxo-4-dimethylphosphonobutyric acid amide

Experiments show that the effect of the compounds on bacteria. Parasites, fungi and plants are based on an inhibition of the l-deoxy-D-xylulose-5-phosphate (DOXP) pathway, which could be detected in these organisms, but not for humans. The following example accordingly shows the effect of the compounds according to the invention on the DOXP reductoisomerase.

Example 9

Inhibition of the enzyme DOXP reductoisomerase from Escherichia coli and Helicobacter pylori The DOXP reductoisomerase from Escherichia coli was expressed as a recombinant protein in E. coli. The activity of the DOXP reductoisomerase was determined in a mixture which contained 100 mM Tris-HCl (pH = 7.5), 1 mM MnCl ₂ 0.3 mM NADPH and 1 mM DOXP. The oxidation was measured in a spectrophotometer at 365 nm. To carry out the inhibition studies, the activity of DOXP reductoisomerase in the presence of compounds 1 and 2 measured in different concentrations between 0.1 nmol l ^"1 and 100 μmol l ^{" 1} . The concentration at which the enzyme is inhibited half-maximally (IC ₅₀ ) was determined from the measured values. The same procedure was used to determine the action of the DOXP reductoisomerase from Helicobacter pylori. The results, ie the IC50 values, are shown in Table I.

Table I

Example 10

Inhibition of the growth of the bacterial species Pseudomonas aeruginosa and Escherichia coli Antibacterial activity of the above compounds

A dilution series with the concentrations 32, 16, 8, 4, 2, 1 and 0 mg 1 ^" 'of the individual compounds 1 to 8 and 11 and 12 was placed in 5 culture tubes in LB medium in a volume of 0.5 ml. The tubes were inoculated with 10 μl each from the overnight culture of E. coli Kl 2 and shaken overnight at 37 ° C. The growth of the bacteria was assessed by turbidity of the medium, the results are shown in Table II.

The antibacterial activity of P. aeruginosa was also determined. The results are also shown in Table II.

Table II

Beispiel 11

Example 11

Inhibition of the growth of Plasmodium falciparum (pathogen of malaria tropica) The antimalarial activity of substances 1 to 12 was determined on in vitro cultures of the malaria pathogen Plasmodium falciparum. The wells of a 96-well microtiter plate were each with 200 μl An asynchronous Plasmodium falciparum culture was loaded at 0.4% parasitemia and 2% hematocrit. A serial dilution series of the compounds was then prepared in three steps between concentrations of 100 μmol l ^"1 and 0.14 nmol l ^{" 1.} The plates were prepared incubated at 37 ° C., 3% CO ₂ and 5% 0 ₂ over a period of 48 hours. Then 30 μl medium supplemented with 27 μCi ml ^"1 [ ³ H] -hypoxanthine were added to each well. After 24 hours of incubation the parasites were harvested by filtration on glass fiber filters and the incorporated radioactivity was measured. The inhibition of the parasite growth was measured as a percentage inhibition of the tritium incorporation Inhibition of parasite growth was expressed as a percentage inhibition of tritium incorporation based on a comparison without substance. The half-maximum inhibitory concentration (IC50) of the substance was determined by extrapolation of the values. The results are shown in Table III.

Table III

Example 12

Herbicidal activity of the monosodium salt of 4-phosphono-N-hydroxybutyric acid amide

The herbicidal action is tested with 4-phosphono-N-hydroxybutyric acid amide monosodium salt as active ingredient by the process known to the person skilled in the art:

The inhibition of the growth of the plants examined is given in percent in the tables. The damage patterns mean:

C: Chlorosis - In the dicotyledonous plants, lightening of the following leaves (chlorophyll degradation = white coloring of the leaves, which inhibits overall growth). The damage pattern in monocotyledonous plants is not quite as noticeable as in dicotyledonous plants. The brightenings are usually only at the tips of the shoots. I: general white coloring of the leaves.

The results are shown in Tables IV to VI. Table IV

HYDRO pre-emergence test substance: 4000 / ha

Table V

EARTH pre-emergence test substance: 2000 / ha

Tabelle VI

Table VI

EARTH post-emergence test substance: 2000 g / ha

Comparable results were obtained for the following compounds: N-hydroxy-3-oxo-4-phosphonobutyric acid amide. N-Hydroxy-N-methy 1-3-oxo-4-phosphonobutyric acid amide. N-hydroxy-4-oxo-4- (P-methyl-phosphonato) butyric acid amide, N-hydroxy-4-ethylphosphonobutyric acid amide

Example 13

Herbicidal activity of the monosodium salt of 4-phosphono-N-hydroxy-N-methylbutyric acid amide

The herbicidal activity is as in Example 12, but with N-4-phosphono-N-hydroxy

N-methylbutyric acid amide sodium salt investigated as an active ingredient. The results are shown in Tables VII to IX.

Table VII

HYDRO-preemergence

Application rate of test substance: 4000 g / ha

- JJ - Table VIII

EARTH pre-emergence

Expenditure of test substance: 2000 / ha

Table IX

EARTH Casserole

Test substance expenditure: 2000 g / ha

Claims

claims 1. Organophosphorus compounds of the general formula (I) Rx 0 0 \ II ιι N-C-A-P-R? (I) / I HO R ₃ in the A for propylene. 2-oxopropylene or 3-oxopropylene. in which R- is selected from the group. that of hydrogen, substituted and unsubstituted alkyl. substituted and unsubstituted hydroxvalkvl. substituted and unsubstituted alkenyl. substituted and unsubstituted alkynyl, substituted and unsubstituted aryl. substituted and unsubstituted acyl. substituted and unsubstituted cycloalkyl. substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical. Halogen and OX-, wherein Xi are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl, substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted aryl. substituted and unsubstituted acyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aralkyl, substituted and unsubstituted heterocyclic radical and R and R _{3 are the} same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxyalkyl. substituted and unsubstituted aryl, substituted and unsubstituted acyl. substituted and unsubstituted aralkyl, substituted and unsubstituted alkenyl. substituted and unsubstituted alkynyl, substituted and unsubstituted cycloalkyl. substituted and unsubstituted heterocyclic radical. Halogen, OX ₂ or OX exists. wherein X ₂ or X _{3 may be the} same or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, substituted and unsubstituted hydroxylalkyl. substituted and unsubstituted aryl, substituted and unsubstituted aralkyl. substituted and unsubstituted alkenyl, substituted and unsubstituted alkynyl, substituted and unsubstituted cycloalkyl, substituted 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 pharmaceutically acceptable salts, esters and amides and salts of the esters. 2. Compounds according to claim 1, characterized in that Ri is selected from the group consisting of a hydrogen radical, a methyl radical, an ethyl radical and a phenyl radical. 3. Compounds according to claim 1 or claim 2, characterized in that R ₂ and R are the same or different and are selected from the group consisting of a methyl radical, an ethyl radical, OX ₂ and OX ₃ . 4. Compounds according to claim 2, characterized in that X ₂ and X _{3 are the} same or different and are selected from the group consisting of sodium, a methyl radical, an ethyl radical and a phenyl radical. 5. Compounds according to claim 1, characterized in that they are selected from the group consisting of N-hydroxy-4-phosphonobutyric acid amide sodium salt, N-hydroxy-N-methyl-4-phosphono-butyric acid amide monosodium salt, N-hydroxy-N-phenyl-4-phosphono-butanoic acid monosodium salt, N-hydroxy-N- (2-hydroxyethyl) -4-phosphono-butanoic acid mono sodium salt, N- (l-carboxypropyl) -N-hydroxy-4- phosphonobutyric acid amide monosodium salt, N-hydroxy-N- (4-imidazolyl) -4-phosphonobutyric acid amide monosodium salt, N-ethyl-N-hydroxy-4-ethylphosphonobutter acid amide monosodium salt, N-benzyl-N-hydroxy-4-ethylphosphonobutyric acid amide monosodium salt, N-allyl-N-hydroxy-4-ethylphosphono-butyric acid amide monosodium salt, N-hydroxy-N- (3- (3-phenylpropionyl) -4-ethylphosphonobutter acid amide monosodium salt, N- (4-fluorobenzyl) -N-hydroxy-4-ethylphosphonobutyric acid amide monosodium salt, N-hydroxy-N-rt-propyl-4-diethylphosphonobutyric acid amide, N-hydroxy-N-orthotolyl-4-diethylphosphonobutyric acid amide, N-but-3-ynyl-N-hydroxy-4-diethylphosphonobutyric acid amide, N- (l-carboxy-2-methyl-propyl) -N-hydroxy-4-diethylphosphonobutyric acid amide, N-hydroxy-N- (2- (4-hydroxy-indol-3-yl) -ethyl) -4- diethyl-phosphonobuttersäureamid, N-hydroxy-N-isopropyl-4-dimemyl-phosphinoxido-butyric acid amide, N-Metα-ethylbenzyl-N-hydroxy-4-dimethyl-phosphinoxido-butyric acid amide, N-cyclohex-2-enyl-N-hydroxy-4-dimethyl- phosphinoxido-butyric acid amide, N- (l-carboxy-2-methyl-butyl) -N-hydroxy-4-dimethylphosphinoxido-butyric acid amide, N-carbamoyl-N-hydroxy-4-dimethylphosphinoxido-butyric acid amide, N - «- Butyl-N-hydroxy-4- (P-methyl-phosphinato) -butyric acid amide, N-hyciroxy-N- (pαrα-isopropylbenzyl) -4- (P-methyl-phosphinato) -butyric acid amide, N-hydroxy- N- (4,4,4-trifluorobutyl) -4- (P-memyl-phosphinato) butyric acid amide, N-carboxymethyl-N-hydroxy-4- (P-methyl-phosphinato) butyric acid amide, N-ethoxycarbonyl-N-hydroxy-4- (P-methyl-phosphinato) -buttersäureamid, N-isobutyl-N-hydroxy-4-oxo-4-phosphono-buttersäureamidmono sodium salt. N-ortbo-chlorophenyl-N-hydroxy-4-oxo-4-phosphono-butyric acid amide monosodium salt, N-cyclohexyl-N-hydroxy-4-oxo-4-phosphono-butyric acid amide mono sodium salt, N- (l-carboxyethyl) -N-hydroxy-4-oxo-4-phosphonobuttersäureamidmononatriumsalz. N-Hydroxy-N- (2- (N-hydroxy-carbamoyl) ethyl) -4-oxo-4-phosphono-butyric acid amide monosodium salt. N-tert-butyl-N-hydroxy-4-ethylphosphono-4-oxo-butyric acid monosodium salt. N-pαrα-nitrophenyl-N-hydroxy-4-ethyl-phosphono-4-oxo-butyric acid amide monosodium salt, N- (4-oxocyclohexyl) -N-hydroxy-4-ethyl-phosphono-4-oxo-butanoic acid monosodium salt, N- (1-carboxy-1-methyl-ethyl) -N-hydroxy-4-ethyl-phosphono-4-oxo-butanoic acid monosodium salt, N- (3-chloro-2,2-dimethyl-propyl) -N-hydroxy-4-ethylphosphono-4-oxo-butanoic acid monosodium salt, N-hydroxy-N-n-pentyl-4-diethyl-phosphono-4-oxo-butyric acid, N-hydroxy-N- (3-acetyl-4-methoxy-phenyl) -4-diethyl-phosphono-4-oxo-butanoic acid amide, N-hydroxy-N- (3-methylcyclohexyl) -4-diethylphosphono-4-oxo-butyric acid, N- (5-Amino-l-carboxy-pentyl) -N-hydroxy-4-diethyl-phosphono-4-oxo-butanoic acid amide. N-hydroxy-N- (3- (N-morpholino) propyl) -4-diethyl-phosphono-4-oxo-butyric acid. N-hydroxy-N-isobutyl-4-dimethyl-phosphono-4-oxo-butyric acid, N-betα-naphthyl-N-hydroxy-4-dimethyl-phosphinoxido-4-oxo-butyric acid. N- (4-hydroxymethyl-2-phenyl-1,3-dioxan-4-yl) -N-hydroxy-4-dimethyl-phosphine-oxido- 4-oxo-butyric acid, N- (l-carboxy-3-methyl-butyl) -N-hydroxy-4-dimethyl-phosphineoxido-4-oxo-butyric acid amide, N- (2-furyl) -N-hydroxy-4-dimethylphosphinoxido-4-oxo-butyric acid, N- (3-methyl-pentyl) -N-hydroxy-4- (P-methyl-phosphinato) -4-oxo-butyric acid, N-Hydroxy-N - (/ 7Jetα-pyridyl) -4- (P-methyl-phosphinato) -4-oxo-butyric acid, N-hydroxy-N- (l-cyano-cyclohexyl) -4- (P-methyl-phosphinato) -4-oxo-butyric acid. N- (1-carboxypentyl) -N-hydroxy-4- (P-methylphosphinato) -4-oxo-butyric acid amide, N- (N-phenyl-carbamoyl) -N-hydroxy-4- (P-methyl-phosphinato) -4-oxo-butyric acid, N-Hydroxy-N - «- octyl-3-oxo-4-phosphonobuttersäureamidmononatriumsalz, N-hydroxy-N- (2-indolyl) -3-oxo-4-phosphonobuttersäureamidmononatriumsalz, N-hydroxy-N-dec-9-enyl-3-oxo-4-phosphono-butyric acid monosodium salt, N- (1-carboxy-3-methylthio-propyl) -N-hydroxy-3-oxo-4-phosphonobutyric acid amide monosodium salt, N-hydroxy-N- (2,2,2-trichloroethyl) -3-oxo-4-phosphono-butyric acid amide monosodium salt, N-decyl-N-hydroxy-3-oxo-4-ethylphosphono-butyric acid amide monosodium salt, N- (2-fluorenyl) -N-hydroxy-3-oxo-4-ethylphosphono-butyric acid amide monosodium salt, N- (1-adamantyl) -N-hydroxy-3-oxo-4-ethyl-phosphono-butyric acid amide monosodium salt, N- (1,4-dioxan-2-yl) -N-hydroxy-3-oxo-4- ethylphosphonobutter acid amide monosodium salt, N- (N- (2,4-Dimethyl-phenyl) carbamoyl) -N-hydroxy-3-oxo-4-ethylphosphonobutyric acid amide monosodium salt. N- (3-methyl-hex-2-yl) -N-hydroxy-3-oxo-4-diethylphosphono-butyric acid amide, N- / meto-tolyl-N-hydroxy-3-oxo-4-diethylphosphono-butyric acid amide, N- (3-acetylaminopropyl) -N-hydroxy-3-oxo-4-diethylphosphono-butyric acid, N- (2-pyrrolidone-4-yl) -N-hydroxy-3-oxo-4-diethylphosphono-butyric acid, N- (2- (Methylsulfoxido) ethyl) -N-hydroxy-3-oxo-4-diethylphosphono-butyric acid, N-dodecyl-N-hydroxy-3-oxo-4-dimethylphosphine oxido-butyric acid amide, N-7 rα-hydroxyphenyl-N-hydroxy-3-oxo-4-dimethylphosphine oxido-butyric acid amide. N- (2-Propionylethyl) -N-hydroxy-3-oxo-4-dimethylphosphinoxido-butyric acid. N- (l-Carboxy-2- (3,4-dihydroxyphenyl) ethyl) -N-hydroxy-3-oxo-4-dimethyl-phosphinoxido-butyric acid amide. N- (3-phosphonopropyl) -N-hydroxy-3-oxo-4-dimethylphosphinoxido-butyric acid amide monosodium salt, N- (3-ethyl-4-methyl-pentyl) -N-hydroxy-3-oxo-4- (P-methyl-phosphinato) butyric acid amide, N- (3-hydroxy-3-phenyl-propyl) -N-hydroxy-3-oxo-4- (P-methylphosphinato) butyric acid amide, N- (2- (2-methoxy-ethoxy) -ethyl) - N-hydroxy-3-oxo-4- (P-methylphosphinato) butyric acid amide, N- (4-imidazolyl-methyl) -N-hydroxy-3-oxo-4- (P-methyl-phosphinato) -buttersäureamid. N- (2- (7- (2- (N, N-Diethylamino) ethoxy) fluoren-9-one-2-yloxy) ethyl) -N-hydroxy-3-oxo-4- (P-methyl -phosphinato) -butyric acid amide, N-hydroxy-4-phosphono-butyric acid amide monosodium salt, N-hydroxy-4- (P-methyl-phosphinato) -buttersäureamid monosodium salt, N-hydroxy-N-methyl-3-oxo-4- (P-methyl-phosphinato) butyric acid amide monosodium salt, N-hydroxy-3-oxo-4- (P-methyl-phosphinato) -buttersäureamid monosodium salt, N-hydroxy-N-methyl-3-oxo-4-phosphono-butyric acid monosodium salt, N-hydroxy-3-oxo-4-phosphono-butyric acid monosodium salt, N-hydroxy-4-diphenylphosphono-butyric acid, N-hydroxy-N-phenyl-4-diphenylphosphono-butyric acid amide, N-hydroxy-N-benzyl-4-phosphono-butyric acid amide monosodium salt, N-hydroxy-N-benzyl-3-oxo-4-dimethylphosphonobuttersäureamid, N-hydroxy-4- (diethylphosphono) -buttersäureamid, N-hydroxy-N-methyl-4- (diethylphosphono) -buttersäureamid, N-hydroxy-4-phosphono-N-hydroxybutyric acid amide, N-hydroxy-N-methyl-4-phosphono-butyric acid amide, N-hydroxy-3-oxo-4- (diethylphosphono) -buttersäureamid) N-hydroxy-N-methyl-3-oxo-4- (diethylphosphono) -buttersäureamid. N-hydroxy-3-oxo-4-phosphono-butyric acid), N-hydroxy-N-methyl-3-oxo-4-phosphono-butyric acid amide), N-hydroxy-3-oxo-4-phosphonobutyric acid amide, N-hydroxy-N-methyl-3-oxo-4-phosphonobuttersäureamid, N-hydroxy-4-oxo-4- (P-methyl-phosphonato) -buttersäureamid, N-hydroxy-4-ethylphosphonobutyric acid amide exists. 6. Compounds according to any one of the preceding claims, characterized in that they are selected from the group consisting of N-hydroxy-4-phosphonobutyric acid amide sodium salt and N-hydroxy-N-methyl-4-phosphonobutyric acid amide monosodium salt. 7. Pharmaceutical preparation, characterized by an effective content of at least one organophosphorus compound according to one of claims 1 to 6 together with a pharmaceutically acceptable carrier. 8. Pharmaceutical preparation according to claim 7, characterized by at least one further pharmaceutical active ingredient. 9. Pharmaceutical preparation according to one of claims 7 or 8, characterized by one or more constituents of the group consisting of sulfonamide, sulfadoxine, artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracyclines , Doxycycline, proguanil, metronidazole, praziquantil, niclosamide, mebendazole, pyrantel, tiabendazole, diethyl carbazine, piperazine, pyrivinum, metrifonate, oxamniquin. Bithionol and Suramin exist. 10. Use of organophosphorus compounds according to one of claims 1 to 6 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. 11. Use according to claim 10 for the treatment of infections caused by bacteria, viruses, fungi or single or multicellular parasites. 12. Use according to claim 10 for the treatment of infections caused by bacteria selected from the group consisting of bacteria of the family Propionibacteriaceae. in particular of the genus Propionibacterium, in particular the species Propionibacterium acnes, bacteria of the Actinomycetaceae family, in particular of the Actinomyces genus. Bacteria of the genus Corynebacterium, especially the species Corynebacterium diphteriae and Corynebacterium pseudotuberculosis, bacteria of the family Mycobacteriaceae, of the genus Mycobacterium, especially the species Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium, bacteria of the Chlamydiaceae family, especially the species Chlamydia trachomatis and Chlamydia psittaci, bacteria of the genus Listeria, in particular the species Listeria monocytogenese, bacteria of the species Erysipidium, bacteria of the species Erysipidium, bacteria of the species Erysipidium, bacteria of the species Erysipia Genus Yersinia, of the species Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica and Yersinia ruckeri, bacteria of the family Mycoplasmataceae, of the genera Mycoplasma and Ureaplasma, in particular the species Mycopiasma pneumoniae, bacteria of the genus Brucella, bacteria of the genus Family Neiseriac, bacteria especially of the family Bordetella the genera Neisseria and Moraxella, in particular the species Neisseria meningitides, Neisseria gonorrhoeae and Moraxella bovis, bacteria of the Vibrionaceae family, in particular the genera Vibrio, Aeromonas, Plesiomonas and Photobacterium, in particular the Species Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas, bacteria of the genus Campylobacter, especially the species Campylobacter jejuni, Campylobacter coli and Campylobacter fetus, bacteria of the genus Helicobacter, especially the species Helicobacter pylori, bacteria of the Spirochaetaceae and Leptospiraceae families, in particular the Treponema, Borrelia and Leptospira species, in particular Borrelia burgdorferi, Actinobacillus bacteria, Legionella-ceae family, the Legionella Bartart family, and the Rickettsiaceae family of bacteria, Bacteria of the genera Nocardia and Rhodococcus, bacteria of the genus Dermatophilus, bacteria of the family Pseudomonadaceae, especially of the genera Pseudomonas and Xanthomonas, bacteria of the family Enterobacteriaceae, especially of the genera Escherichia, Klebsiella, Proteus, Providencia, Salmonella, Serratia and Shigella, bacteria of the family Pasteurellaceae, especially of the genus Haemophi- lus. Bacteria of the Micrococcaceae family. especially the genera Micrococcus and Staphylococcus. Bacteria of the Streptococcaceae family, in particular the genera Streptococcus and Enterococcus, and bacteria of the Bacillaceae family. in particular the genera Bacillus and Clostridium, and in Helicobacter eradication therapy for ulcers of the gastrointestinal tract. 13. Use according to claim 10 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 viruses, 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, in particular smallpox viruses, Orthopox-Parapox, Molluscum-Contagiosum virus, Aviviruses, Capriviruses, Leporipoxviruses, primarily hepatotropic viruses, especially hepatitis viruses, such as Hepatitis A viruses, Hepatitis B viruses, Hepatitis C viruses D-Niren, hepatitis E viruses. Hepatitis F viruses, Hepatits G viruses, hepadnaviruses, in particular all hepatitis viruses, such as hepatitis B virus, hepatitis D viruses, viruses of the Genus Picornaviridae, 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 , Orbiviruses, rotaviruses, viruses of the genus Togaviridae, in particular togaviruses, alpha viruses, rubiviruses, pestiviruses, rubella virus, viruses of the genus Flaviviridae, in particular flaviviruses. TBE virus, hepatitis C virus, viruses of the Orthomyxoviridae genus. 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, Lyssavirus, viscular stomatitis virus, viruses of the Gavirida virus, viruses of the Gavir virus , especially Bunya viruses, Νairovirus. Phlebovirus, uukuvirus, hantavirus, viruses of the genus Arenaviridae, in particular arena viruses, lymphocytic choriomeningitis virus, viruses of the genus Retroviridae, in particular retroviruses, all HTL viruses, human T-cell leukemia virus, oncornaviruses, spumaviruses, lentiviruses Viruses, viruses of the genus Filoviridae, in particular Marburg and Ebola viruses, slow viruses, prions, oncoviruses and leukemia viruses exist. 14. Use according to claim 10 for the prevention and treatment of infections ver caused by unicellular parasites, namely pathogens of malaria, sleeping sickness, Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis. pneumocystosis, balantidiosis, cryptosporidiosis. sarco cystosis. the Akantha-Möbose. the nail rose. coccidiosis, giardiosis and lambliosis. 15. Method for the therapeutic and prophylactic treatment of infectious diseases caused by bacteria. Fungi or parasites, in which a therapeutically effective amount of a compound according to any one of claims 1 to 6 is administered to a patient suffering from an infection caused by bacteria, fungi or parasites. 16. A method for combating undesirable plant growth, characterized in that useful plants or their cropland are treated with an effective amount of a compound according to any one of claims 1 to 6 or an agent containing such a derivative.