SK9502001A3 - Use of 3-isoxazolidinones and hydroxylamine acids for the treatment of infections - Google Patents

Abstract

The invention relates to medicaments containing at least one compound of the formula (I) and to their use for the therapeutic and prophylactic treatment of bacterial, fungal and parasitic infections in humans and animals.

Description

Technical field

The invention relates to the use of 3-isoxazolidinones and hydroxylamino acids as well as their salts, esters and ester salts as active ingredients for the therapeutic and prophylactic treatment of infections caused by bacteria, fungi and parasites in humans and animals.

BACKGROUND OF THE INVENTION

There is a need for medicaments for treating humans and animals that have potent activity against infections.

It is therefore an object of the present invention to provide a compound which can be used in humans and animals in infections with bacteria, fungi and parasites and which satisfies the above conditions.

U.S. Pat. No. 4,405,357 discloses 3-isoxazolidinones and hydroxyl amino acids as herbicides.

Surprisingly, it has now been found that the above-mentioned task is solved by 3-isoxazolidinones and hydroxylamino acids. This group of substances exhibits an anti-infective effect against bacteria, fungi, unicellular and more cellular parasites. According to the invention, single-cell parasites are understood to be protozoa.

SUMMARY OF THE INVENTION

According to the invention, the compounds contained in the medicaments correspond to the general formula I:

R 3 (R) wherein R 3 is selected from the group consisting of hydrogen, alkyl, alkoxy- (C 0-6) -alkyl, C 3-14 -cycloalkyl- (C 0-6) -alkyl, cycloalkoxy- (C 0-6) alkyl, amino- (C 0-2) -alkyl, silyl- (C 0-6) -alkyl, thio- (C 0-6) -alkyl, wherein each alkyl radical and each alkoxy radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl group saturated or unsaturated, with one or more double or triple bonds and substituted by hydroxy, amino, halogen, oxo and alkoxy radicals, and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or S,

R 4 is selected from the group consisting of hydrogen, alkyl radicals, acyl radicals and cycloalkyl- (C 0-6) -alkyl, wherein each alkyl radical and each acyl radical may be branched or unbranched and each alkyl radical, each acyl radical and each cycloalkyl radical a saturated or unsaturated group having one or more double or triple bonds and substituted by hydroxy, amino, halogen, oxo- and alkoxy radicals and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms,

R 1 and R ₂ are the same or different and are selected from the group consisting of hydrogen, hydroxy, halogen, amino, alkyl, alkoxy and cycloalkyl- (C 0-6) -alkyl, wherein each alkyl radical may be and each branched or unbranched alkoxy radical and each amino radical, alkyl radical, each alkoxy radical and each cycloalkyl group saturated or unsaturated, with one or more double or triple bonds and substituted with hydroxy, amino, halogen, oxo- and alkoxy radicals, and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur atoms,

R 5, R 6 and R 7 are the same or different and are selected from the group consisting of hydroxy, halogen, alkyl, cycloalkyl- (C 0-6) -alkyl, cycloalkoxy- (C 0-6) -alkyl, alkoxy- (Co-26) -alkyl groups, amino groups, thio- (Co-2-6) -alkyl groups and acyl radicals, wherein each alkyl radical, each alkoxy radical and each acyl radical may be branched or non-branched and each alkyl radical , each alkoxy radical and each cycloalkyl group saturated or with one or more double or triple bonds unsaturated and substituted with hydroxy, amino, halogen, oxo and alkoxy radicals and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur, alternatively R 5 with R 1 may form a ring and R 3 and R 6 may form a ring; they may exhibit a single carbon-oxygen bond by forming a ring structure.

The invention also includes pharmaceutically acceptable salts, esters and ester salts.

. The same or different R 1 and R 2 are preferred and selected from the group consisting of substituted and unsubstituted alkyl groups, most preferably C 1 -C 4 alkyl groups.

It is preferably selected from the group consisting of hydrogen, substituted and unsubstituted alkyl groups, preferably C 1 -C ₄ -alkyl groups, substituted and unsubstituted aromatic C 7 -C ₁₄ -cycloalkyl groups, pyranyl, tert-butyldimethylsilyl and

--C-R ₈ wherein R _g is selected from the group consisting of substituted and unsubstituted, preferably halogen-substituted alkyl, substituted and unsubstituted cycloalkyl- (Co-26) alkyl, substituted or unsubstituted amino, substituted and unsubstituted alkoxy groups, substituted and unsubstituted phenoxy, substituted and unsubstituted alkylthio, substituted and unsubstituted, preferably unsubstituted or halogen-, methyl-, methoxy, nitro-, amino- or CF3- substituted aromatic cycloalkylthio groups.

R 4 is preferably selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted phenyl radicals, and

wherein X is selected from the group consisting of hydrogen, halogen, C 1 -C 4 alkyl radicals and phenyl radicals and Y is selected from the group consisting of hydrogen, halogen, C 1 -C 4 -alkyl radicals, nitro radicals, methoxy-, methylenedioxy radicals, wherein n is 0 or 1.

R @ 2 is preferably selected from the group consisting of hydrogen and halogen, or R @ 3 and R @ ₇ have a single carbon-oxygen bond by forming a ring structure.

Particularly preferred are compounds wherein R 1 and R 2 are independently selected from the group consisting of methyl and ethyl,

R 5 and R 6 are independently selected from the group consisting of hydrogen, chloro, bromo and methoxy.

Particular preference is given to compounds in which R 4 is

X

wherein X is selected from the group consisting of 2-chloro, 2-bromo, 2-fluoro- and Y is selected from the group consisting of 4-chloro, 4-bromo, 4-fluoro, 5-fluoro- and 4,5-methylenedioxy, wherein n is 0 or 1.

Particularly preferred are compounds in which R; and R 2 are methyl, R 3 and R 7 are hydrogen, or contain a carbon-oxygen bond that forms a ring structure.

r r

Examples of preferred compounds are 3-chloro-N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro N-hydroxy-N-phenyl-2,2-dimethylpropanamide, N- (2-bromophenyl) methyl-3-chloro-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N-hydroxy- 2,2-Dimethyl-N- (2-methylphenyl) methylpropanamide, 3-chloro-N-hydroxy-2,2, N-trimethylpropanamide, 3-chloro-N-hydroxy-2,2-dimethyl- N- (phenylmethyl) -propanamide, 3-chloro-N- (2,4-dichlorophenylmethyl) -N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N- (2-chlorophenyl) methyl 1N -methoxy-2,2-dimethylpropanamide, 3,3-dichloro-N (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N- (2-fluorophenyl) m ethyl 1-N-hydroxy-2,2-dimethylpropanamide, 3-bromo-N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, N-benzoyloxy-3-chloro-N- (2- chlorophenyl) methyl-2,2-dimethylpropanamide, N-acetoxy-3-chloro-N- (2-chlorophenyl) methyl-2,2-dimethylpropanamide, N- (chloroacetoxy) -3-chloro-N- (2-chlorophenyl) -m ethyl-2,2-dimethylpropanamide, 2- (2-chlorophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenyl-3-isoxazolidinone, 2- (2-bromophenyl) methyl- 4,4-dimethyl-3-isoxazolidinone, 4,4-dimethyl-2- (2-methylphenyl) methyl-3-isoxazolidinone, 2,4-trimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenylmethyl-3- isoxazolidinone, 2- (2,4-dichlorophenyl) -methyl-4,4-dimethyl-3-isoxazolidinone, 5-chloro-2- (2-chlorophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, 2- ( 2-chlorophenyl) methyl-5-methoxy-4,4-dimethyl-3-isoxazolidinone, 2- (2-fluorophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, N- [2- (2-chlorophenyl) methyl] -N, 3-dihydroxy-2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N- (methylaminocarbonyloxy) propanamide, 3-chloro-N [( 2-chlorophenyl) ethyl] -N - [(2-tetrahydrofuran-1-yl) oxy] -2,2-dimethylpropanamide,

3-Chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N- [dimethyl (1,1-dimethylethyl) siyloxy] propanamide, 3-acetoxy-N - [(2-chlorophenoxy) methyl -N-hydroxy-2,2-dimethylpropanamide, 2 - [(2-chloro-4-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone,

2 - [(2-chloro-5-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2,4,5-trifluorophenyl) methyl] -4,4-dimethyl- 3-isoxazolidinone, 2 - [(2-chloro-6-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-ethoxy-4,4-dimethyl- 3-isoxazolidione, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-phenylamino-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-hydroxy-4,4-dimethyl- 3-isoxazolidinone,

3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(phenylamino) carbonyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2 -dimethyl-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N-phenoxycarbonyloxy) propanamide, 3-chloro-N - [(2C-chlorophenyl) methyl] -N-ethoxycarbonyl- oxy-2,2-dimethyl propanamide, N-benzoyloxy-3,3-dichloro-N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, N - [(2-bromophenyl) methyl] - 3,3-Dichloro-N-hydroxy-2,2-dimethyl-propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N- (4-nitrobenzoyloxy) -2,2-dimethyl-propanamide, 3-chloro - N - ((2-chlorophenyl) methyl) -2,2-dimethyl-N - [(2-methylphenyl) carbonyloxy] propanamide,

3-chloro-N-dichloroacetoxy - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(4-methylphenyl) sulfonyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-1 - N - [(1,1-dimethylmethylene) carbonyloxy] propanamide, 3-chloro- N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(ethylthiocarbonyl) oxy] propanamide, 3-chloro-N - [(2,2,2-trichloroethoxy) carbonyloxy] -N - [(2-chlorophenyl) methyl] -2,3-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) aminocarbonyloxy)] - N - [(2-chlorophenyl) methyl] -2,2-dimethyl propanamide, 3-chloro-N - [(4-chlorophenyl) aminocarbonyloxy)] - N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2 2-dimethyl-N- (phenylmethoxy) propanamide, 3-chloro-N - [(2,4-dichlorophenoxy) acetoxy] -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro- N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(3-trifluoromethyl) benzoyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl N - [(4-methylphenyl) aminocarbonyl oxy)] propane amide, 3 -chloro-N - [(2-chlorophenylmethyl) -N - [(3,4-dichlorophenyl) aminocarbonyloxy)] - 2,2-dimethylpropanamide, 3-chloro-N- (3-chloro-2,2-dimethyl-1-oxopropoxy) ) -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N-hydroxy-

2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(2-fluorophenyl) aminocarbonyl-oxy] -2,2-dimethyl propanamide, 3-chloro-N- [(2-chlorophenyl) methyl] -N - [(4-methoxyphenyl) aminocarbonyloxy] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(3-trifluoro) methylphenyl) aminocarbonyloxy] -2,2-dimethyl propanamide, 3-bromo-N - [(2-chlorophenyl) methyl] -N- (methylaminocarbonyloxy) -2,2-dimethylpropanamide, 3-bromo-N- (2-chloroacetoxy) -N - [(2-chlorophenyl) methyl] -2,2-trimethyl propanamide, 3-chloro-N- [2,5-dichloro (formylamino) benzoyloxy] -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N-

2-Chloro-6-ethoxy-2,2-dimethyl-propanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N (methylcarbonyl oxy) -2,2-dimethyl-propanamide, 3-bromo N - [(2-bromophenyl) methyl] N - [(2-chlorophenyl) aminocarbonyl oxy] -2,2-dimethylpropanamide, 2 - [(2-chlorophenyl) methyl] -N-hydroxy-2,2 -dimethyl-3-methylthio-propanamide, 3-phenyl-carbonyloxycarbonyloxy-N - [(2-chlorophenyl) methyl] -N-hydroxy-2,2-dimethylpropanamide, 2 [(4-chlorophenyl) methyl] -4,4 -dimethyl-3-isoxazolidinone, 2 - [(3,4-dichlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3- isoxazolidinon-5-yl acetate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-ylbenzoate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl ethyl 3-isoxazolidinon-5-yl-dichloroacetate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-yl-phenylcarbamate,

2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-ylmethylcarbamate, 2 - ((2-chloro-4-cyanophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-5-methoxyphenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-4-methoxyphenyl) methyl] -4,4-dimethyl 1-3-isoxazolidinone, 2 - [(2,4-difluorophenyl) -triethyl] -4,4-dimethyl-

3-isoxazolidinone, 2 - [(4-bromo-2-chlorophenyl) methyl] -4,4-dimethyl-1-3-isoxazolidinone, 2 - [(2-bromo-4-fluorophenyl) methyl] -4,4- di-methyl-3-isoxazolidinone, 2 - [(6-chloro-

1,3-benzodioxo-5-yl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-phenoxy-3- isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-imety-1-5- (1-methyloxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-di methyl 5- (phenyl-1-methoxy) -3-isoxazolidinone, 2 - [(2-bromophenyl) methyl] -5-chloro-4,4-dimethyl-3-isoxazolidinone, 2 - [(2,5-dichlorophenyl) methyl -4,4-Dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) -methyl] -4,4-dimethylethoxy-3-isoxazolidinone, 2 [( 2-chloro-phenyl) -4,4-dimethyl-5- (2-propenyloxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2-propinyloxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-1-5- (2-methoxyethoxy) -3-isoxazolidinone, 2 - [(4-fluoro-2-iodophenyl) methyl] - 4,4-Dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-cyclopentoxy-4,4-dimethyl-1-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4 4-dimethyl-5- (4-nitrophenoxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-cyclopropylmethoxy-4,4-dimethyl-1-3-isoxazolidinone, 2 - [(2-bromophenyl) methyl] -4,4-dimethyl-5 (2-phenoxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (3-butyl) methyl Noxy) -4,4-diethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (2-butinoxy) -4,4-dimethyl-1-

3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (3-butenoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-pentoxy-4 4-Dimethyl-3-isoxazolidinone, 2 [(2-chlorophenyl) methyl] -5-hexoxy-4,4-dimethyl-1-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (1-methylpropoxy) -4,4-dimethyl 1-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (3-methyl 1-3-butenoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-fluorin-1-ol)

r r. f r <

tert -butylphenyl] -5-butoxy-4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -

4,4-dimethyl-3-isoxazolidinone.

Examples of the above definitions and suitable examples thereof are given below.

Acyl is a substituent that is derived from an acid, an organic carboxylic acid such as carbonic acid, carbamic acid or the individual aforementioned corresponding to a thioacid or an imidacid or an organic sulfonic acid, which acids include relevant organic, aromatic and / or heterocyclic groups such as carbamoyl or carbamimidoyl.

Suitable examples for these acyl groups are given in the following.

Aliphatic acyl groups are acyl residues derived from aliphatic acids and 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.); alkylcarbamoyl (e.g., methylcarbamoyl, etc.); (N-alkyl) -thiocarbamoyl (e.g., (N-methyl) -thiocarbamoyl, etc.); alkylcarbamimidoyl (e.g., methylcarbamimidoyl, etc.); oxalo; alkoxalyl (e.g., methoxalyl, etoxalyl, propoxalyl, etc.).

In the above examples of aliphatic acyl groups, the aliphatic hydrocarbon moiety, in particular the alkyl group and the carbohydrate moiety, may be aliphatic. an alkane radical, optionally having 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; preferred aliphatic acyl radicals with such substituents may be mentioned

C r e.g. amino, carboxy, amino and carboxy, halogen, acylamino or the like substituted alkanoyls.

Aromatic acyl radicals are those which are derived from an acid having a substituted or unsubstituted aryl group, wherein the aryl group may include phenyl, tolyl; xyl, naphthyl and the like; suitable examples are given in the following:

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 and 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 moiety (especially the aryl moiety) and / or the aliphatic hydrocarbon moiety (especially the alkane moiety) may optionally have one or more suitable substituents, such as those already mentioned as suitable substituents for the alkyl group and the alkyl group, respectively. alkane residue. Particularly and as examples of preferred aromatic acyl radicals with particular substituents, mention may be made of amino-, halo-hydroxy- or halo- and acyloxy-substituted aroyl and hydroxy-, hydroxyimino-, dihaloalkanoyloxyimino-substituted aralkanoyl and arylthiocarbamoyl (e.g. phenylthiocarbamoyl). );

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

A heterocyclic acyl radical is an acyl radical derived from an acid having a heterocyclic group; this includes:

heterocyclic carbonyl wherein the heterocyclic moiety is an aromatic or aliphatic 5- to 6-membered heterocycle with at least one heteroatom selected from nitrogen, oxygen and sulfur (e.g., thiophenyl, furoyl, pyrrolecarbonyl, nicotinoyl, etc.);

heterocycloalkanoyl wherein the heterocyclic moiety is an aromatic or aliphatic 5- to 6-membered heterocycle and has at least one nitrogen, oxygen and sulfur heteroatom (e.g., thiophenylacetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino-4-thiazolyl) (-2-methoxyiminoacetyl, etc.) and the like.

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

Alkyl, unless otherwise defined, is an alkyl radical of up to 26 carbon atoms, straight or branched chain such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl and the like. It may be substituted e.g. hydroxy, amino, halogen- (e.g. fluorine, bromine, chlorine), oxo and alkoxy radicals such as methoxy, ethoxy radicals.

The alkoxy radical, unless otherwise defined, is an alkoxy radical of up to 26 carbon atoms, straight-chain or branched such as methoxy, ethoxy and the like. It may be substituted by hydroxy, amino, halogen, oxo and alkoxy radicals such as methoxy, ethoxy.

Alkoxy- (C 0-6) -alkyl groups are alkoxy radicals which can be attached to the basic skeleton via an alkyl radical. Alkyl and alkoxy groups are as defined above.

Cycloalkyl- (C 0-6) -alkyl radicals, unless otherwise defined, are cyclic compounds having 3 to 8 carbon atoms, which are bonded to the backbone directly or via an alkylene moiety. The alkylene moiety may be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloalkyl radical are, inter alia, alkoxy radicals, alkyl radicals, hydroxyl radicals, halogen radicals, amino radicals, oxo radicals. Cycloalkyl groups can also be aromatic with the appropriate number of double bonds. be aryl- (C 0-2) -alkyl radicals (e.g., phenyl, pyridyl, naphthyl, etc.). Particularly aromatic cyclic compounds may further contain substituents such as nitro, CF 3 and phenyl residues.

Cycloalkoxy- (C 0-26) -alkyl groups are cyclic compounds having 3 to 8 carbon atoms, which are bonded to the backbone directly via oxygen or via an alkylene moiety. The alkylene moiety may be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloalkyl radical are, inter alia, alkoxy radicals (also alkylenedioxy radicals, such as methylenedioxy-), alkyl radicals, hydroxyl radicals, halogen radicals, amino radicals, oxides. Cycloalkyl groups can also be more cyclic and aromatic with the appropriate number of double bonds (e.g., phenoxy, pyridoxy, naphthoxy, etc.). Particularly aromatic cyclic compounds may further contain substituents such as nitro, CF 3 and phenyl radicals.

For example, amino radicals may be substituted with alkyl radicals or cycloalkyl- (C 0-6) -alkyl radicals as defined above.

Amino- (Co-26) -alkyl groups are amino radicals which can be attached to the basic skeleton via an alkyl radical. Alkyl and amino groups are as defined above.

For example, silyl radicals may be substituted with alkyl radicals or cycloalkyl- (C 0-26) -alkyl radicals as defined above.

Silyl- (Co-26) -alkyl groups are silyl radicals which can be attached to the basic skeleton via an alkyl radical. Alkyl and silyl groups are as defined above.

For example, thio- (C 0-6) -alkyl groups may be substituted by alkyl radicals as defined above or by cycloalkyl- (C 0-26) -alkyl radicals. (Co26) -alkyl groups are straight-chain or branched alkylene radicals, such as methylene, ethylene, propylene, isopropylene, butylene, isobutylene, isobutylene, pentylene, hexylene and the like. They may contain double or triple bonds and may be substituted by e.g. hydroxyl residues, amino residues.

r f e r> 'e r r <t ·. ·

Π r: rr <rrrcr <nrr · f. ^r r

.......

halogen residues (e.g., fluorine, bromine, chlorine), oxides and alkoxy residues such as methoxy, ethoxy.

Compounds of formula I according to the invention containing, for example, double bonds or chiral R1 groups to R7 allow the presence of spatial isomers. The use of the compounds of the invention encompasses all the spatial isomers as well as the pure compounds in the form of mixtures thereof.

The compounds are particularly useful for the therapeutic and prophylactic treatment of human and animal in infections caused by bacteria, monocell and multicellular parasites and fungi.

The compounds are effective against unicellular parasites (protozoa), in particular against agents of malaria and sleeping sickness, as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcardiosis, coccorosis, acantamebosis, acantamebebosis .

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

The active compounds according to the invention are particularly useful against the following bacteria:

bacteria of the family Propionibacterium, in particular the genus Propionibacterium, in particular the species Propionibacterium acnes, bacteria of the family Actinomycetaceae particular genus Actinomyces, bacteria of the genus Corynebacterium, particularly Corynebacterium diphtheriae and Corynebacterium pseudotuberculosis, bacteria of the family Mycobacteriaceae, genus Mycobacterium, in particular Mycobacterium leprae, Mycohacterium tuberculosis, Mycobacterium bovis and Mycobacterium avium, bacteria of the family Chlamydiaceae, in particular species Chlantydia trachomatis and Chlamydia psittaci, bacteria of the genus Listeria in particular of the species Listeria monocytogenes, bacteria of the genus Erysipelthrix rhusiopathiae, bacteria of the genus Clostridium, bacteria of the genus Yersinia, Yersinia ' >

r i: '<. r ir rr <crc * enterocolitica and Yersinia ruckeri, bacteria of the family Mycoplasmataceae, genera Mycoplasma and Ureaplasma, in particular Mycoplasma pneumoniae, bacteria of the genus Brucella, bacteria of the genus Bordetella, bacteria of the family Neisseriaceae and Neisseriaceae, especially Neisseriaceae, and Moraxella bovis, bacteria of the family Vibrionaceae, in particular genera Vibrio, Aeromonas, Plesiomonas and Photobacterium, in particular Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas, bacteria of the Campylobacter species, in particular Campylobdcter jejuni species, Campylobacter fetus rhodium, Campylohacter coli, Campylohacter Helicobacter pylori, bacteria of the family Spirochaetaceae and Leptospiraceae, in particular of the genera Treponema, Borrelia and Leptospira, especially Borrelia burgdorferi, bacteria of the genus Actinobacillus, bacteria of the family Legionellaceae, genus Legionella, bacteria of the family Redeettse Nocardia and Rhodococcus strains, Dermatophilus spp., Pseudomonadaceae, in particular Pseudomonas and Xanthomonas spp., Enterobacteriaceae spp. Micrococcaceae, especially the genera Micrococcus and Staphylococcus, bacteria of the family Streptococcaceae, especially the genera Streptococcus and Enterococcus, and bacteria of the family Bacillaceae, especially the genera Bacillus and Clostridium.

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

Furthermore, the use of Helicobacter eradication in gastric and intestinal ulcers is beneficial.

Combinations with another antibiotic may also be used to treat the above-mentioned diseases. Isoniazide, rifampicin, etambutol, pyrazinamide, streptomycin, protonamide and dapson are particularly suitable for the combination of preparations with other antiinfectives for the treatment of tuberculosis.

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

Pharmaceutically acceptable salts of the compounds include those which, in their protonated form, form 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.

Also particularly pharmaceutically suitable are salts such as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylammonium salt, dicyclohexylamine salt, and amino acid salts such as arginine salt, aspartic acid salt, glutamic acid salt.

The activity of the substances is determined by a system of experiments. This system is based on measuring the inhibition of the growth of bacteria, parasites or fungi in vitro. Experimental procedures which are well known to those of ordinary skill in the art are used in part.

For example, inhibition of malaria parasite growth in blood cultures is determined to determine antimalarial activity.

The determination of antibacterial activity is based on the measurement of bacterial growth inhibition on nutrient media and in liquid cultures.

The determination of fungicidal activity is based on the inhibition of fungal growth on the culture medium and in liquid cultures.

Some of the microorganisms to be studied can only be studied in animal models. The corresponding models will be used here.

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

Pharmaceutically active compositions may be prepared in the form of pharmaceutical preparations in dosage units. That is, the composition is available in the form of individual particles, e.g. dragée tablets, capsules, pills, suppositories and ampoules, in which the active substance content corresponds to a fraction or more of a single dose. Dosage units may contain e.g. 1, 2, 3 or 4 single doses or 'Λ,' / ₃ or% of a single dose. A single dose contains the best amount of active ingredient to be administered when administered, which generally corresponds to half or a third or a quarter of the daily dose.

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

Pharmaceutical preparations include tablets, coated tablets, capsules, pills, granules, lace, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays. Tablets, dragees, capsules, pills, and granules may contain the active ingredients in addition to conventional carriers such as (a) fillers and extenders, e.g. starches, milk sugar, raw sugar, glucose, mannitol and silicic acid, (b) binders, e.g. carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, (c) humectants, e.g. (d) raising agents, e.g. agar-agar, calcium carbonate, sodium carbonate, (e) retardants, e.g. (f) resorption accelerators e.g. quaternary ammonium compounds; (g) wetting agents, e.g. cetyl alcohol, glycerol monostearate, (h) adsorbents, e.g. kaolin and bentonite; and (i) antiadhesives, e.g. talc, calcium and magnesium stearate and solid polyethylene glycols, or mixtures of the substances mentioned under (a) to (i).

r. yyy • s cerr · e * yy yy f! frr r. · ^r ^ ''

Tablets, dragees, capsules, pills, and granules may optionally be provided with coatings and shells containing opalescent agents, and may also be formulated to deliver the active ingredients only or preferably in a certain part of the intestinal tract, optionally elongated, e.g. . polymeric substance and waxes.

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

The suppositories may contain, in addition to the active ingredients, conventional, water-soluble or water-insoluble carriers, e.g. polyethylene glycols, fats, e.g. cocoa butter and higher esters (e.g., C 14 -alcohol with C 16 -fatty acid) or mixtures thereof.

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

Powders and sprays may contain, in addition to the active ingredients, conventional carriers, e.g. milk sugar, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures thereof. Sprays may additionally contain conventional propellants, e.g. chlorofluorocarbons.

The solutions and emulsions may contain, in addition to the active ingredients, conventional carriers such as solvents, solubilizers and emulsifiers, e.g. water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, glycerol, , tetrahydrofurfuryl alcohol, polyethylene glycols and sorbitan fatty acid esters or mixtures thereof.

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

• err _; nrrrrc

- .. - ·;

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

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

In particular, the active compounds of the formula I are to be present in the abovementioned pharmaceutical preparations in a concentration of from about 0.1 to 99.5% by weight, preferably from about 0.5 to 95% by weight of the total mixture.

In addition to the compounds of formula I, the pharmaceutical preparations may also contain other pharmaceutically active substances.

The compounds can be used together with the antibacterial substances described so far; antiviral, antifungal and antiparasitic properties. In particular, these include compounds which have already found use in therapy or are still in use. Particularly suitable for this purpose are the substances listed together in Rote Liste or Simon / Stille, Antibiotics-Therapy in Klinik und Praxis,

9. vyd. 1998 ,, Schattauer Verlag or under http: Zwww.customs.treas.gov/impexp/ruling/harmoniz/hrm 129.html on the Internet. In particular, they may be penicillin derivatives, benzylpenicillin (penicillin G), phenoxypenicillins, isoxazolylpenicillins, aminopenicillins, ampicillin, amoxixillin. bacampicillin, carboxypenicillin, ticarcillin, temocillin, acyalaminopenicillins, azlocillin, meslocillin, piperacillin, apalcillin, mecilinam, cephalosporins, cefazoline group, cefuroxime group, cefoxitin, cefoxime, cefotime, cefotime, , cefpirom, cefepime, other cephalosporins, cefsulodine, cefoperazone, cephalexin group oralcephalosporins, loracarbef, cefprozil, new extended spectrum oralcephalosporins, cefixime, cefpodoxime-proxetil, cefuroxime-cetime, cefuroxime-axetil, cefuroxime-axetil, , carbapenem, imipenem / cilastatin, meropenem, biapenem, aztreonam, an inhibitor of β-lactamase, acid • t ^rr '' lina clavulanate / amoxicillin, clavulanic acid / ticarcillin, sulbactam / ampicillin, tazobactam / piperacillin, tetracycline, oxytetracycline, rolitetracycline, doxycycline, minocycline, chloramphenicol, aminoglycosides dyamycin, tobramycin, netilmicin, amikacin, spectinomyxin, macrolides, erythromycin, clarithromycin, roxithromycin, azithromycin, dirithromycin, spiramycin, josamycin, linkosamide, cleptamycin, glycidicin, fusidinicin, fusidinicin, fusidinicin foliage, sulfonamides, Co-trimoxazole, trimethoprim, other combinations of diaminopyridine-sulfonamide, nitrofurans, nitrofurantoin, nitrofurazone, gyrase inhibitors (quinolones), norfloxacin, ciprofloxacin, ofloxacin, sparfloxacin, foxloxacin, foxloxacin, enoxacin, enoxacin, enoxacin -bacterial agents, isoniazid, rifampicin, rifabutin, etambutol, pyrazinamide, streptomycin, capreomycin, protonamide, terizidone, dapson, clofazimine, topical antibiotics, bacitracin, tyrotricin, polymyxins, antiviromycin, acomycin, acamycin, kanamycin, kanamycin, clovir, azidothymidine, didanosine, zalcitabine, tiacytidine, stavudine, ribavirin, idoxuridine, trifluridine, foscarnet, amantadine, interferons, tibolderivatives, proteinase inhibitors, antifungals, polyenes, amphotericin B, nyazin, azazole, azazole, terametium, natamycin , itraconazole, fluconazole, UK-109.496, topical azoles, clotrimazole, econazole, isoconazole, oxiconazole, bifonazole, flucytosine, griseofulvin, ciclopiroxolamine, tolnaftate, naphthifine, terbinafine, amorolfine, anthraquinones, anthraquinones, betrachinones, betrachinones, betrachinones, betrachinones, betrachinones, betrachinones , quinine, quinidines, mefloquine, halofantrine, chloroquine, amodiaquine, acridine, benzonaphthyridine, mepacrine, pyronaridine, dapson, sulfonamides, sulfadoxin, sulfalene, trimethoprim, proguanil, chloroproguanil, diaminopyrimidine, priminopyrrine, pyracholine, pyrachetamine, pyrachinamine, pyracholine clindamycin, norfloxacin, ciprofloxacin, ofloxacin, ar temizinin, dihydroartemizinin, 10b artemether, arteether, atrtesunat, atovaquone, suramine, melarsoprol, nifurtmox, sodium stibogluconate, pentamidine, amphotericin B, metronidazole, clioquinol, mebendazole, niclozamide, pyazranquine, tazranquelbine, praziquantin, , piperazine, embonate.

r r

Furthermore, the phosphororganic compounds may exist in the pharmaceutical compositions in combination with sulfonamide, sulfadoxin, artemisinin, atovaquone, quinine, chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesine, tetracycline, methoxylcillazole, proxycyclazolide, proxycyclazolide, , diethylcarbazine, piperazine, pyrivinum, metrifonate, oxamnichine, bitionol or suramine or in combination with a plurality of such substances.

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

Said preparations may be used in humans and animals either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously), intracisternally, intravaginally, intraperitoneally, locally (powders, ointments, drops) and for the treatment of infections in the hollow areas, body cavities. Injectable solutions, solutions and suspensions for oral therapy, gels, poured formulations, emulsions, ointments or drops are suitable formulations. Ophthalmic and dermatological formulations, silver and other salts, ear drops, eye ointments, powders or solutions can be used for topical therapy. In animals, intake can also take place in suitable formulations in feed or drinking water. Gels, powders, powders, tablets, prolonged-action tablets, premixes, concentrates, granules, pellets, tablets, boluses, capsules, aerosols, sprays, inhalants can also be used in humans and animals. The compounds of the invention may be further incorporated into other carrier materials such as e.g. Synthetic materials (plastic chains for local therapy), collagen or bone cement.

In general, in both human and veterinary medicine, it has proven advantageous to administer the active compound (s) of formula I in total amounts of from about 0.05 to about 600, in particular 0.5 to 200 mg / kg of body weight for 24 hours to achieve the desired results. hours, optionally in the form of multiple individual doses. A single dose contains the active compound (s) in particular in amounts of from about 1 to about 200, in particular from 1 to 60 mg / kg body weight. However, it may be desirable to deviate from the aforementioned dosage, depending on the type and body weight of the patient to be treated, the type and severity of the disease, the type of preparation and the administration of the medicament, as well as the time span, respectively. the interval within which the administration takes place. Thus, in some cases, it may be sufficient to start with less than the amount of active ingredient given above, while in other cases the amounts of active ingredient must be exceeded. The precise determination of the optimal dosage required and the method of application of the active ingredients can be made by the skilled person on the basis of his expert knowledge.

The compounds of the invention may be administered to animals in the usual concentrations and formulations together with feeding and / or feeding. feedingstuffs or drinking water.

Methods for preparing compounds of the invention are known to those skilled in the art, e.g. from US-P-4,405,357.

DETAILED DESCRIPTION OF THE INVENTION

The following illustrates the efficacy of some of the compounds of the invention by way of examples.

The following compounds have been studied:

Substance 2:

r r e t r

i * e r r r t r e · r c p r r.

e c <yy yy

Substance 3:

Experiments have shown that the effect of the compounds is to inhibit the metabolism of 1-desoxy-D-xylulose-5-phosphate (DOXP), which can be detected in bacteria, parasites and fungi, but not in humans. The following example accordingly shows the effect of the compounds of the invention on DOXP-reductoisomerase.

Example 1

DOXP-reductoisomerase from Escherichia coli was expressed in E. coli as a recombinant protein. DOXP-reductoisomerase activity was determined in a batch containing 100 mM Tris-HCl (pH = 7.5), 1 mM MnCH, 0.3 mM NADPH, and 1 mM DOXP. The oxidation of NADPH was measured with a 265 nm spectrometer. To perform inhibition studies, DOXP reductoisomerase activity was measured in the presence of substances 1-4 at various concentrations between 0.1 and 100 gmol / L. From the measured values, the concentration at which the enzyme is half inhibited (IC 50) was determined. Results ie. IC50 values are given in the table.

re ^rr '

Example 2

Malaria efficacy of Substance 1 to 4 was determined in vitro on Plasmodium falciparum cultures of malaria. Wells in a 96-well microtiter plate were equipped with 200 μΐ asynchronous culture of Plasmodium falciparum at 0.4% parasitemia and 2% hematocrit. Subsequently, a series of series of substance dilutions between concentrations of 100 to 0.14 μηιοί / ΐ were made in triplicate systems. Plates were incubated at 37 ° C, 3% CO 2 and 5% O ₂ for 48 hours. Then, 30 μΐ of medium supplemented with 27 μϋΐ / ιηΐ [ ³ H] -hypoxanthin was added to each well. After 24-hour incubation, the parasites were collected by filtration on glass fiber filters and the incorporated radioactivity was measured. Inhibition of parasite growth was measured as percent inhibition of tritium incorporation. Inhibition of parasite growth was, as a percentage inhibition of tritium incorporation, relative to no substance comparison. By extrapolating the values, half the maximum inhibitory concentration (IC 50) of the substance was determined. Results ie. IC50 values are given in the table below:

Claims (12)

PATENT CLAIMS Use of at least one compound of formula I R5 Ri QR ₄ where R ₃ is selected from the group consisting of hydrogen, alkyl, alkoxy (Co-26) -alkyl, C ₃ .i4-cycloalkyl- (Co-26) alkyl, cycloalkoxy (Co-6 2) -al alkyl group, and m neno- (C 0-6) -alkyl, silyl- (C 0-2) -alkyl and thio- (C 0-6) -alkyl, wherein each alkyl radical and each alkoxy radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl saturated or unsaturated, with one or more double or triple bonds and substituted with hydroxy, amino, halogen, oxo and alkoxy radicals, and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or S, R 4 is selected from the group consisting of hydrogen, alkyl radicals, acyl radicals and cycloalkyl- (. ₂ 6) -alkyl, which may each alkyl radical and each acyl radical branched or straight and each alkyl radical, each acyl radical and each saturated or unsaturated cycloalkyl with one or more double or triple bonds and substituted with hydroxy, amino, halogen, oxo and alkoxy radicals and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, R 1 and R 2 are the same or different and are selected from the group consisting of hydrogen, hydroxy-, halogen-, substituted and unsubstituted amino groups, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, and substituted and unsubstituted cycloalkyl- (C 0-6) each alkyl radical and each alkoxy radical may be branched or unbranched and each alkyl radical, each alkoxy radical and each cycloalkyl radical may be saturated or unsaturated, with one or more double or triple bonds, and one or two carbon atoms cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms, R 5, R 6 and R 7 are the same or different and are selected from the group consisting of hydroxy, halogen, substituted and unsubstituted C 1-6 -alkyl, substituted and unsubstituted cycloalkyl- (C 0-2) alkyl, substituted and unsubstituted cycloalkoxy- (Co-26) alkyl groups, substituted and unsubstituted cycloalkoxy- (Co-26) alkyl groups, substituted and unsubstituted amino groups, and substituted and unsubstituted thio- (Co-26) -alkyl groups, and substituted and unsubstituted acyl radicals, each of which may be an alkyl radical, each alkoxy radical and each acyl radical branched or unbranched, and each alkyl radical, each alkoxy radical and each cycloalkyl group may be saturated or unsaturated, with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl group may be replaced by nitrogen, oxygen or sulfur, alternating R ₅ with R 1 may form a ring and R 3 and R 7 may show a single carbon-acid bond to form a ring structure, or a pharmaceutically acceptable salt, ester or ester salt thereof, for the prophylactic or therapeutic treatment of infections that are induced bacteria, parasites or fungi. t * r y r y r y r y y,, r 25 ú / '/ Use according to claim 1, wherein R 1 and R 2 are or different and selected from the group consisting of substituted and unsubstituted alkyl groups, preferably C 1 -C 4 -alkyl groups. Use according to any one of the preceding claims, wherein R 3 is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl, preferably C 1 -C 4 -alkyl, substituted and unsubstituted aromatic C 7 -C 14 -cycloalkyl, pyranyl, tert-butyldimethylsilyl and -c —R ₈ wherein R 8 is selected from the group consisting of substituted and unsubstituted, preferably halogen substituted alkyl, substituted and unsubstituted cycloalkyl- (C 0-6) -alkyl, substituted and unsubstituted amino, substituted and unsubstituted alkoxy, substituted, and unsubstituted, substituted and unsubstituted alkylthio groups, substituted and unsubstituted aromatic cycloalkylthio groups, preferably aromatic cycloalkylthio groups, which are substituted or unsubstituted by halogen-, methyl-, methoxy, nitro-, amino- or CF3- groups Use according to any one of the preceding claims, wherein R ₄ is selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted phenyl radicals, and wherein X is selected from the group consisting of hydrogen, halogen, C 1 -C 4 alkyl radicals and phenyl radicals and Y is selected from the group consisting of tert hydrogen, halogen, C 1 -C 4 -alkyl radicals, nitro radicals, methoxy radicals, methylenedioxy radicals, wherein n is 0 or 1. Use according to claim 4, wherein X is selected from the group consisting of chloro, bromo, fluoro and Y is selected from the group consisting of 4-chloro, 4-bromo, 4-fluoro, 5-fluoro- and 4,5 - methylenedioxy, wherein n is 0 or 1. Use according to any one of the preceding claims, wherein R 2 is selected from the group consisting of hydrogen and halogen, or R 3 and R 7 show a single carbon-oxygen bond in such a way as to form a ring structure. Use according to any one of the preceding claims, wherein R 1 and R ₂ are independently selected from the group consisting of methyl and ethyl, R 5 and R 6 are selected from the group consisting of hydrogen, chloro, bromo and methoxy. The use according to any one of the preceding claims, wherein R 1 and R ₂ are methyl, R 3 and R 7 are hydrogen or contain a carbon-oxygen bond which forms a ring structure. Use according to claim 8, characterized in that it contains at least one substance selected from the group consisting of 3-chloro-N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, N- ( 2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N-hydroxy-N-phenylc 27 .... 2,2-dimethylpropanamide, N- (2-bromophenyl) methyl-3-chloro-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N-hydroxy-2,2-dimethyl-N- (2-methylphenyl) methylpropanamide , 3-chloro-N-hydroxy-2,2-N-tri-methyl propanamide, 3-chloro-N-hydroxy-2,2-dimethyl-N- (phenylmethyl) propanamide, 3-chloro-N- (2,4- dichlorophenyl 1-methyl) -N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N- (2-chlorophenyl) methyl-N-methoxy-2,2-dimethylpropanes d 3,3-dichloro-N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N- (2-fluorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, 3-bromo-N- (2-chlorophenyl) methyl-N-hydroxy-2,2-dimethylpropanamide, N-benzoyloxy-3-chloro-N (2-chlorophenyl) methyl-2,2-dimethylpropanamide , N-acetoxy-3-chloro-N- (2-chlorophenyl) methyl-2,2-dimethylpropanamide, N- (chloroacetoxy) -3-chloro-N- (2-chlorophenyl) methyl-2,2-dimethylpropanamide, 2- (2 (chlorophenyl) methyl 1-4,4-dimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenyl-3-isoxazolidinone, 2- (2-bromophenyl) methyl-4,4-dimethyl-1-3-isoxazolidinone, 4 4-Dimethyl-2- (2-methylf enyl) methyl-3-isoxazolidinone, 2,4-trimethyl-3-isoxazolidinone, 4,4-dimethyl-2-phenylmethyl-3-isoxazolidinone, 2- (2,4-dichlorophenyl) methyl-4,4-methyl-1- 3-isoxazolidinone, 5-chloro-2- (2-chlorophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, 2- (2-chlorophenyl) methyl-5-methoxy-4,4-dimethyl-3-isoxazolidinone, 2- ( 2-fluorophenyl) methyl-4,4-dimethyl-3-isoxazolidinone, N [2- (2-chlorophenyl) methyl] -N, 3-dihydroxy-2,2-dimethylpropanamide, 3-chloro N - [(2-chloro) (phenyl) methyl] -2,2-dimethyl-N- (methyl aminocarbonyloxy) propane d, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(2-tetrahydropyrano) oxy] -2,2-dimethyl-propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N [dimethyl (1,1-dimethylethyl) silyloxy] propanamide, 3-acetoxy-N - [(2) -chlorophenoxy) methyl] -N-hydroxy-2,2-dimethyl propanamide, 2 - [(2-chloro-4-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro-5-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2,4,5-trichlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone 2 - [[2-chloro-6-fluorophenyl) met yl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-ethoxy-4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4 4-dimethyl-5-phenyl-1-amino-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5-hydroxy-4,4-dimethyl-3-isoxazolidinone, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(phenylamino) carbonyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2 2-dimethyl-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N-phenoxycarbonyloxy) propanamide, 328 chloro-N - [(2-chlorophenyl) methyl] -N-ethoxycarbonyloxy-2,2-dimethylpropanamide, N-benzoyloxy-3,3-dichloro-N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, N - [(2-bromophenyl) methyl] -3,3-dichloro-N-hydroxy- 2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N- (4-nitrobenzoyloxy) -2,2-dihydroxypropanamide, 3-chloro-N - [(2-chlorophenylmethyl) -2, 2-Dimethyl-N - [(2m ethylphenyl) carbonyloxy] propanamide, 3-chloro-N-dichloroacetoxy - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl 1] -2,2-dimethyl-N - [(4-methylphenyl) sulfonyloxy] propanamide, 3-chloro-N [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(1) , 1-dimethylethyl) carbonyloxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(ethylthiocarbonyl) oxy] propanamide, 3-chloro-N - [(2, 2,2-trichloroethoxy)] -N- [(2-c chlorophenyl) methyl] -2,3-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) aminocarbonyloxy)] - N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N- [ (4-chlorophenyl) aminocarbonyloxy)] - N - [(2-chlorophenyl) methyl] - 2,2-di-methyl propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N (phenylmethoxy) propanamide, 3-chloro-N - [(2,4-dichlorophenoxy) acetoxy N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(3) -trifluoromethyl) benzoyl oxy] propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -2,2-dimethyl-N - [(4-methylphenyl) aminocarbonyloxy)] propanamide, 3-chloro-N - [(2 -chlorophenylmethyl] -N - [(3,4-dichlorophenyl) aminocarbonyloxy)] - 2,2-dimethylpropanamide, 3-chloro-N- (3-chloro-2,2-dimethyl-1-oxopropoxy) -N - [(2- chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N-hydroxy-2,2-dimethylpropanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(2-fluorophenyl) aminocarbonyloxy] - 2,2-methyl propanamide, 3-chloro-N - [(2-chlorophenyl) methyl] -N - [(4-methoxyphenyl) aminocarbonyloxy] -2,2-dimethylpropanamide, 3-chloro-N - [(2-chloro) (phenyl) methyl] -N - [(3-trifluoromethylphenyl) amino carbonyloxy] -2,2-dimethylpropanamide, 3-bromo-N - [(2-chlorophenyl) methyl] -N- (methylaminocarbonyloxy) -2,2-dimethylpropanamide, 3-bromo-N- (2-chloro-acetoxy) -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-chloro-N- [2,5-dichloro (formyl-amino) benzoyloxy] -N - [(2-chlorophenyl) methyl] -2,2-dimethylpropanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N-2-chloroacethoxy -2,2-dimethylpropanamide, 3-bromo-N - [(2-bromophenyl) methyl] -N- (methylcarbonyloxy) -2,2-dimethylpropanamide; 3-Bromo-N - [(2-bromophenyl) methyl] -N - [(2 chlorophenyl) aminocarbonyloxy] -2,2-dimethylpropanamine 1,2 - ((2-chlorophenyl) methyl) -N-hydroxy-2, 2-dimethyl-3-methylthiopropanamide, 3-phenylcarbonyloxy-N - [(2-chlorophenyl) methyl] -N-hydroxy-2,2-dimethylpropanamide, 2 - ((4-chlorophenyl) methyl) -4,4-dimethyl -3-isoxazolidinone, 2 - ((3,4-dichlorophenyl) methyl] -4,4-dimethyl 1-3-isoxazolidinone, 2 - [(chlorophenyl) methyl] -4,4-dimethyl- 3-isoxazolidinon-5-yl acetate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-1-3-isoxazolidinon-5-yl benzoate, 2 - [(chlorophenyl) methyl] -4, 4-Dimethyl-3-isoxazolidinon-5-yl-dichloroacetate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-1-3-isoxazolidinon-5-yl-phenylcarbamate, 2 - [(chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinon-5-ylmethylcarbamate, 2 - [(2-chloro-4-cyanophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chloro- 5-methoxyphenyl) methyl] -4,4-dimethyl- 3-isoxazolidinone, 2 - [(2-chloro-4-methoxyphenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - ((2,4-difluorophenyl) methyl] -4,4- di-methyl-3-isoxazolidinone, 2 [(4-bromo-2-chlorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-bromo- 4-fluorophenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(6-chloro-1,3-benzdioxol-5-yl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5-phenoxy-3-isoxazolidinone, dimethyl-5- (1-methylethoxy) -3-isoxazolidinone, dimethyl 1-5- l-methoxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,42 - [(2-chlorophenyl) methyl] -4,42 - [(2-bromophenyl) methyl] -5-chloro-4,4-dimethyl-3-isoxazolidinone, 2 - ((2,5-Dichloro-phenyl) methyl] -4,4-dimethyl-3-isoxazolidinone, 2 - ((2-chlorophenyl) methyl) -4,4-dimethyl-5-propoxy-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2 -propenyloxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (2-piperinyloxy) -3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4, 4-Dimethyl-5- (2-methoxyethoxy) -3-isoxazolidinone, 2 - [(4-fluoro-2-iodophenyl) methyl] -4,4-dimethyl-1-3-isoxazolidinone, 2 - [(2- chlorophenyl) methyl] -5-cyclopentoxy-4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl-5- (4-nitrophenoxy) -3-isoxazolidinone, 2- [ (2-chlorophenyl) methyl] -5-cyclopropylmethoxy-4,4-dimethyl-3-isoxazolidinone, 5- (2-propinoxy) -3-isoxazolidinone, xyl) -4,4-dimethyl-1-3-isoxazolidinone, xyl) -4,4-dimethyl-1-3-isoxazolidinone, oxy) -4,4-di methyl-3-isoxazolidinone. 2 - [(2-bromophenyl) methyl] -4,4-dimethyl- 2 - [(2-chlorophenyl) methyl] -5- (3-butino2 - [(2-chlorophenyl) methyl] -5- (2-butino2 - [(2-chlorophenyl) methyl] -5- (3-buten2- [(2-chlorophenyl) methyl] -5-pentoxy-4,4-dimethyl-3-isoxazolidinone, 2 - ((2-chlorophenyl) methyl] -5-hexoxy-4,4'-trans; 4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] -5- (1-methylpropoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenyl) methyl] 5- (3-methyl- 3-butenoxy) -4,4-dimethyl-3-isoxazolidinone, 2 - [(2-chlorophenylmethyl) -5-butoxy-4,4-dimethyl-3-isoxazolidinone, and 2 - [(2-chlorophenyl) methyl] -4,4-dimethyl 3-isoxazolidinone. Use according to any one of claims 1 to 9 for the prophylaxis and treatment of infections caused by unicellular parasites, in particular agents of malaria, sleeping sickness, Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, balantidiosis, cryptantebebebrosis, sptaposporebebis. naeglerosis, coccidiosis, giardiasis and lambliosis. Use according to any one of claims 1 to 9 for the prophylaxis and treatment of infections caused by bacteria selected from the group consisting of bacteria of the family Propionibacteriaceae, in particular of the genus Propionihacterium, in particular of the species Propionibacterium acnes, bacteria of the family Actinomycetaceae, in particular of the genus Actinomycesory. in particular Corynebacterium diphteriae and Corynebacterium pseudotuberculosis species, Mycobacteriaceae genus, Mycobacterium genus, in particular Mycobacterium leprae species, Mycobacterium tuberculosis species, Mycobacterium bovis species and Mycobacterium aviurn species, Chlamydia bacterium species Chlamydia bacteria, Chlamydia bacteria, Chlamydia bacteria , Erysipelthrix rhusiopathiae, Clostridium, Yersinia, Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica and Yersinia ruckeri, Mycoplasmataceae, Mycop lasma and Ureaplasma, in particular Mycoplasma pneumoniae, Brucella, Bordetella, Neisseriaceae, in particular Neisseria and Moraxella, in particular Neisseria meningitides, Neisseria gonorrhoeae and Moraxella bovis, Vihrionaceae in particular, Vihrionaceae, Vihrionaceae, Vihrionaceae, Vihrionaceae, and Photobacterium, especially species. Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas, Campylobacter species, in particular Campylobacter jejuni, Campylobacter coli and Campylobacter fetus, Helicobacter spp., Especially Helicobacter pylori spp. , bacteria of the genus Actinobacillus, bacteria of the family Legionellaceae, genus Legionella, bacteria of the family Rickettsiaceae and family Bartonellaceae, bacteria of the genera Nocardia and Rhodococcns, bacteria of the genus Dermatophilus, bacteria of the family Pseudomonadaceae, in particular genus Pseudomonadaceae, , Providencia, Salmonella, Serratia and Shigella, bacteria of the family Pasteurellaceae, in particular of the genus Haemophibus, bacteria of the family Micrococcaceae, in particular of the genera Micrococcus and Staphylococcus, bacteria of the family Streptococcaceae, in particular of the genera Streptococcus and Enterococcus and bacteria of the family Bacillaceae, in particular of the genera Bacillus and Clostridium, and in the eradication therapy of Helicobacter in gastric and intestinal ulcers. A method of treating infectious diseases caused by bacteria, fungi or parasites, characterized in that a therapeutically effective amount of a compound according to any one of claims 1 to 11 is administered to a patient having a disease caused by an infection caused by bacteria, fungi or parasites.