MXPA97000886A - New oxazolidinones sustitui - Google Patents

Abstract

The present invention relates to novel substituted oxazolidinones, of general formula (I) in which the substituents have the meaning indicated in the description, process for their manufacture and their use as a medicament, especially as an antibacterial medicament

Description

New substituted oxazolidinones DESCRIPTION OF THE INVENTION The present invention relates to novel substituted oxazolidinones, a process for their production and their use as a medicament, especially as an antibacterial medicament. For the publications US 5 254 577, US 4 705 799, EP 311 090, EP 312 000 and C.H. Park et al., J. Med. Chem. 5., 1156 (1992), N-aryloxazolidinones with antibacterial activity are known. In addition, 3- (substituted nitrogen) -phenyl1-5-beta-a-idomethyl-oxazolidin-2-ones are known from EP 609 905 Al. Furthermore, in EP 609 491 and EP 657 440, oxazolidinone derivatives with an inhibiting action of monoamino-oxidases are disclosed and in EP 645 376 with action as an antagonist of the adhesion receptors. Also disclosed are oxazolidinone derivatives with antibacterial activity in our patent applications EP 694 543, EP 693 491, EP 694 544, EP 697 412 and EP 738 726. The present invention relates to novel substituted oxazolidinones of general formula (I) REF: 24088 in which A represents a 5-membered aromatic heterocycle directly attached through a carbon atom, with up to 3 heteroatoms of the group S, N and / or O, which may also possess a benzyl ring or • condensed naphthyl, or represents an aromatic heterocycle with a nitrogen atom, at least, of 6 links, attached directly through a carbon atom, or represents a bi- or tricyclic aromatic residue, each • of 6 links, attached directly through a carbon atom, with a ring, at least, containing nitrogen, or represents ß-carbolin-3-yl or indolizinyl attached directly through the 6-membered ring, the cycles being, if necessary, respectively up to trisustituldos by identical or different substituents carboxy, halogen, cyano, mercapto, formyl, phenyl, trifluoromethyl, nitro, alkoxy, alkoxycarbonyl, alkylthio or acyl, linear or branched, with up to 6 carbon atoms respectively, or by linear or branched alkyl or alkenyl with up to 6 carbon atoms respectively, which, in turn, can be substituted by phenyl, and / or are substituted by pyridyl which, in turn, can be substituted by linear or branched alkyl or alkoxy with up to 6 carbon atoms respectively, or represents a remainder of formula wherein R4, R5, R6 and R7 are the same or different and mean hydrogen or carboxy, halogen, cyano, formyl, trifluoromethyl, nitro, linear or branched alkyl with up to 6 carbon atoms or a group of formula -C0-NR13R, in where R13 and R are the same or different and mean hydrogen, linear or branched alkyl with up to 4 carbon atoms or phenyl, R2, R8, R9, R10, RH and R12 are the same or different and mean hydrogen, cycloalkylcarbonyl or cycloalkyl with 3 a 6 carbon atoms respectively, or alkoxycarbonyl or alkylthio, linear or branched, with up to 6 carbon atoms respectively, or means linear or branched alkyl with up to 10 carbon atoms which, if necessary, is substituted by cyano, trifluoromethyl, halogen, phenyl, hydroxyl, carboxyl, linear or branched alkoxycarbonyl with up to 6 carbon atoms, aryl with 6 to 10 carbon atoms, siloalkyl with 3 to 6 carbon atoms and / or a group of formula - (C0) c-NR1SR16, R, 7 -N-S02-R18, Rl9R20-N-SO2- or R21-S (0) d, where c means a number o or l, R15, R16 and R17 have the meaning indicated above for R13 and Rw and are the same or other than these, or form, together with the nitrogen atom, a saturated heterocycle of 5 to 6 links, optionally with another heteroatom of the series N, S and / or O which in turn may, if necessary, also be substituted in another nitrogen atom by linear or branched alkyl or acyl with up to 3 carbon atoms, R18 and R21 are the same or different and mean straight or branched alkyl with up to 4 carbon atoms, benzyl, phenyl or tolyl, or mean linear or branched acyl with up to 6 carbon atoms thatif appropriate, it is substituted by trifluoromethyl, .trichloromethyl or by a group of formula -OR22, where R22 means hydrogen or straight or branched alkyl with up to 6 carbon atoms which, if appropriate, is substituted by aryl with up to 10 carbon atoms. carbon atoms, or mean a group of formula - (CO ^ -NR ^ R24, NR - ^ - SO ^ 26, R27R28-NS02- OR R »-S (0) f where e has the meaning indicated above for cy is the same as or different from this, R23 and R24 and R25 have, respectively, the meaning indicated above for R15, R16 and R17 and are the same or different from these, R27 and R28 have the meaning indicated above for R13 and R14 and they are the same or different from these, f has the meaning indicated above for d and is the same or different from this, R26 and R29 have respectively the meaning indicated above for R18 and R21 and are the same or different from these, D means an atom of oxygen or a residue of the formula -S (0) f, where g means a number or 0, 1 or 2, E and L are the same or different and mean an oxygen atom or one of sulfur, G, M, T and Q are the same or different and mean an oxygen or sulfur atom or a group of formula -NR30, wherein R30 means hydrogen or linear or branched alkyl with up to 5 carbon atoms, a and b are the same or different and mean a number 1 or 2, represents a remainder of the formula wherein R31 means linear or branched alkyl with up to 7 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, phenyl or a group of formula -NR38R39, 'wherein R38 and R39 have the meaning indicated above for R13 and R14 and are the same or different from these, R32 means hydrogen , cyano, cycloalkyl with 3 to 6 carbon atoms, phenyl or linear or branched alkyl with up to 7 carbon atoms, R33 means hydrogen, linear or branched alkyl with up to 7 carbon atoms, phenyl, cycloalkyl with 3 to 6 carbon atoms or a group of formula -NR4 ^ 41, wherein R40 and R41 have the meaning indicated above for R13 and R14 and are the same or different from these, h means a number 1, 2, 3 6 4, R34 means hydrogen, linear or branched alkyl with up to 6 carbon atoms or benzyl, R35 and R36 are the same or different and mean hydrogen or linear alkyl or branched with up to 6 carbon atoms, or R1 represents cyano or represents a saturated, partially unsaturated or unsaturated heterocycle of 5 to 7 links with up to 3 heteroatoms of group S, N and / or 0 which, if necessary, is also up to which is unsubstituted by a N-function by the same or different substituents benzyl, halogen or by linear or branched alkyl with up to 5 carbon atoms and their salts. Physiologically innocuous salts of the substituted oxazolidinones can be salts of the substances according to the invention with mineral acids, carboxylic acids or sulfonic acids. Especially preferred are, for example, salts with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfadic acid, toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, acetic acid, propionic acid, lactic acid, tartaric acid, citric acid , fumaric acid, maleic acid or benzoic acid. Mention may be made, as salts, of salts with customary bases, such as, for example, salts with alkali metals (for example, sodium or potassium salts), alkaline earth salts (for example, calcium or magnesium salts) or ammonium salts, derived from ammonia or from organic amines such as, for example, diethylamine, triethylamine, ethyldiisopropylamine, procaine, dibenzylamine, N-methylmorpholine, dihydroabietylamine, 1-efenamine or methylpiperidine. In addition, reaction products with (C, -C 4) alkyl halides can also act as salts; they act especially with (C, -C4) alkyl iodides. Heterocycle represents, in general, a 5- to 6-membered, saturated or unsaturated ring which, as heteroatoms, can contain up to 3 oxygen, sulfur and / or nitrogen atoms. Preferred are thienyl, furyl, pyrrolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, thiazolyl, oxazolyl, imidazolyl, pyrrolidinyl, piperidinyl or piperazinyl.

These also include saturated 5- to 6-membered saturated heterocycles which can contain, as heteroatoms, up to 2 oxygen atoms, sulfur and / or nitrogen, such as, for example, piperidyl, morpholinyl or piperazinyl or pyrrolidinyl. Especially preferred are piperidyl, morpholinyl and pyrrolidinyl. Hydroxyl protecting group, in the context of the above definition, represents, in general, a protective group of the ratio: tri-ethylsilyl, triisopropylsilyl, t-butyl-dimethylsilyl, benzyl, benzyloxycarbonyl, 2-nitrobenzyl, 4-nitrobenzyl, t -butyloxycarbonyl, allyloxycarbonyl, 4-methoxybenzyl, 4-methoxybenzyloxycarbonyl, tetrahydropyranyl, formyl, acetyl, trichloroacetyl, 2,2,2-trichloroethoxycarbonyl, oxyethoxymethyl, (2- (trimethylsilyl) ethoxy) methyl, benzoyl, 4-methylbenzoyl, 4- nitrobenzoyl, 4-fluorobenzoyl, 4-chlorobenzoyl or 4-methoxybenzoyl. Acetyl, t-butyldimethylsilyl or tetrahydropyranyl are preferred. Amino protecting groups within the scope of the invention are the amino protecting groups commonly used in peptide chemistry. These include, preferably: benzyloxycarbonyl, 2,4-dimethoxybenzyloxycarbonyl, 4-methoxy-benzyloxycarbonyl, methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, allyloxycarbonyl, phthaloyl, 2,2,2-trichloroethoxycarbonyl, fluorenyl-9-methoxyxicarbonyl, formyl, acetyl, 2-chloroacetyl, 2, 2, 2-trifluoroacetyl, 2,2,2-trichloroacetyl, benzoyl, 4-chlorobenzoyl, 4-bromobenzoyl, 4-nitrobenzoyl, phthalimido, isovaleroyl or benzyloxymethylene, 4-nitrobenzyl , 2,4-dinitrobenzyl, 4-nitrophenyl, 4-methoxyphenyl or triphenylmethyl. The compounds according to the invention can exist in stereoisomeric forms which either behave as an object and its mirror image (enantiomers) or do not behave as an object and its mirror image (diastereomers). The invention relates both to the enantiomers or diastereomers and also to their respective mixtures. The racemic forms can be separated, as well as the diastereomers, in known manner, into the individual stereoisomeric components. Preferred are compounds of the general formula (I), in which A represents quinolyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, pyridyl, pyridazyl or thienyl linked respectively through a carbon atom which, if appropriate, are up to trisubstituted by identical substituents or various fluoro, chloro, bromo, phenyl or by alkyl or alkylthio, linear or branched, with up to 4 carbon atoms respectively, or by linear or branched alkenyl with up to 4 carbon atoms which, in turn, may be substituted by phenyl, and / or are substituted by pyridyl which, in turn, can be substituted by linear or branched alkyl or alkoxy with up to 5 carbon atoms respectively, or represents a radical of formula wherein G means an oxygen or sulfur atom, L means an oxygen or sulfur atom, R8 means linear or branched alkyl or alkylthio with up to 6 carbon atoms respectively, R3, R4 and R5 are the same or different and mean hydrogen -, fluorine, chlorine or bromine, represents a formula residue wherein R31 means straight or branched alkyl with up to 5 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or a group of formula -NR3R39, wherein R38 and R39 are the same or different and mean hydrogen, methyl or ethyl, R32 means hydrogen, cyano, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or straight or branched alkyl with up to 5 carbon atoms, R33 means hydrogen, linear or branched alkyl with up to 5 carbon atoms, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or a group of formula -NR4 ^ 41, wherein R40 and R41 have the meaning indicated above for R38 and R39 and are the same or different from these, h means a number 1, 2, 3 or 4, R34 means hydrogen, alkyl linear or branched with up to 4 carbon or benzyl atoms, R35 and R36 are the same or different and mean hydrogen or linear or branched alkyl with up to 4 carbon atoms, or RI represents cyano or rep The thienyl, oxazolyl, thiazolyl, isoxazolyl or pyrazolyl which, if appropriate, is also unsubstituted via an N-function by the same or different substituents benzyl, fluorine, chlorine, bromine or by linear or branched alkyl with up to 3 carbon atoms and its salts. Especially preferred are compounds according to the invention of general formula (I), in which they represent quinolyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, pyridyl, pyridazyl or thienyl linked respectively through a carbon atom which, if appropriate, are up to a by identical or different substituents fluoro, chloro, bromo, phenyl, by alkyl or alkylthio, linear or branched, with up to 3 carbon atoms respectively, or by linear or branched alkenyl with up to 3 carbon atoms which, in turn, may be substituted by phenyl, and / or substituted by pyridyl which, in turn, can be substituted by linear or branched alkyl or alkoxy with up to 4 carbon atoms respectively, or represents a radical of formula wherein G means an oxygen or sulfur atom, L means an oxygen or sulfur atom, R8 means linear or branched alkyl with up to 4 carbon atoms, R3, R4 and R5 are the same or different and mean hydrogen, fluorine, chlorine or bromine, represents a remainder of formula _C- 3"- <? -RM -« "- (CHA-O-R" wherein R31 means linear or branched alkyl with up to 4 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or a group of formula -NR38R39, wherein R38 and R39 are the same or different and mean hydrogen or methyl, R32 means hydrogen, cyano, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl , phenyl or linear or branched alkyl with up to 4 carbon atoms, R33 means hydrogen, linear or branched alkyl with up to 4 carbon atoms, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or a group of formula -NR4 * ^ 41, in where R4o and R4i have the meaning indicated above for R38 and R39 and are the same or different from these, h means a number 1, 2, 3 or 4, R34 means hydrogen, linear or branched alkyl with up to 3 carbon atoms or benzyl , R35 and R36 are the same or different and denote hydrogen or linear or branched alkyl with up to 3 carbon atoms, or R1 represents cyano or represents thienyl, thiazolyl, isoxazolyl or pyrazolyl which, given the It may also be up to and including N-substituted by identical or different substituents benzyl, fluorine, chlorine, bromine or by linear or branched alkyl with up to 3 carbon atoms and their salts. They are especially preferred, in addition, compounds of general formula (I) in which A represents quinolyl, pyridyl or pyridazyl linked respectively through a carbon atom which, if appropriate, are substituted as indicated above. Also especially preferred are compounds of general formula (I) in which A represents benzothiophenyl or thienyl linked respectively through a carbon atom which, if appropriate, are substituted as indicated above. Furthermore, compounds of general formula (I) in which A represents benzothiazolyl or benzoxazolyl linked respectively through a carbon atom which, if appropriate, are substituted as indicated above, are especially preferred. Also especially preferred are compounds of general formula (I) in which A represents a radical of formula wherein R3, R4, Rs and R8 may have the meanings indicated above. Also especially preferred are compounds of the general formula (I) in which R 1 represents a radical of the formula in which R 31 is defined as above. Further preferred are, in addition, compounds of general formula (I) in which R 1 represents a radical of formula wherein R32 and R33 are defined as above. Further preferred are, in addition, compounds of general formula (I) in which R 1 represents a radical of formula wherein h and R34 are defined as above. Further preferred are, in addition, compounds of general formula (I) in which R 1 represents a radical of formula wherein R3S and R36 are defined as above. Further preferred are, in particular, compounds of general formula (I) in which R 1 represents cyano or represents thienyl, thiazolyl, isoxazolyl or pyrazolyl which, if appropriate, may also be unsubstituted via an N function by the same or different substituents benzyl, fluorine, chlorine, bromine or linear or branched alkyl with up to 3 carbon atoms. A process for the production of the compounds according to the invention of general formula (I) was also found, characterized in that they are transformed: [A] Compounds of general formula (II) wherein A has the meaning indicated above, with compounds of general formula (III) R'-Y (III) in which R1 has the meaning indicated above, and Y represents, depending on R1, hydrogen, halogen or represents linear or branched C, -C 4 alkoxy or oxyalkoxycarbonyl, or [B] Compounds of general formula (IV) wherein A has the meaning indicated above, R37 represents (C, -c4) alkyl, with compounds of general formula (V) NH2-Rr (V) in which R1 'represents one of the heterocycles indicated above as R1 or with ethyl dithioacetate in inert solvents, optionally in the presence of a base, and in the case of the S-oxides, oxidation is carried out according to customary methods and, if appropriate, other substituents are introduced or derived. or functional groups already present following usual methods such as, for example, alkylation, redox reactions, substitution reactions and / or saponifications or addition and dissociation of protecting groups.

The processes according to the invention can be clarified in an exemplified manner by the following scheme of formulas: Co or solvent, depending on the individual process steps, ordinary solvents that do not change under the reaction conditions are suitable. These preferably include alcohols such as methanol, ethanol, propanol or isopropanol, or ethers such as diethyl ether, dioxane, 1,2-dimethoxyethane, tetrahydrofuran, glycol dimethyl ether or t-butyl methyl ether, or ketones such as acetone or butanone, or amides such as dimethylformamide or triamide. of hexamethylphosphoric acid, or hydrocarbons such as hexane, benzene, dichlorobenzene, xylene or toluene, or dimethylsulfoxide, acetonitrile, ethyl acetate, or halogenated hydrocarbons such as methylene chloride, chloroform or carbon tetrachloride, or pyridine, picoline or N-methylpiperidine. Mixtures of the solvents mentioned can also be used. As bases, the inorganic or organic base bases are suitable, depending on the individual process steps. These preferably include alkali hydroxides such as, for example, sodium or potassium hydroxide, or alkali carbonates such as sodium or potassium carbonate, or alkali alcoholates, such as, for example, sodium or potassium methanolate, or sodium or potassium ethanolate, or organic amines such as ethyldiisopropylamine, triethylamine, picoline, pyridine or N-methylpiperidine, or amides such as sodium amide or lithium-diisopropyl ida, or lithium-N-silylalkylamides such as, for example, lithium-N- (bis) triphenylsilylamide or alkyl lithium, as n- Butyl lithium The base is used in a ratio of 1 mol to 10 mol, preferred from 1 mol to 3 mol, respectively referred to 1 mol of the compounds of general formulas (III) and (IV). All the transformations are carried out, in general, at normal, high or reduced pressure (for example, from 0.5 bar to 5 bar). In general, normal pressure is used. The compounds of general formulas (III) and (V) are known or obtainable by customary methods. The compounds of general formula (II) are, in part, new and can be obtained by converting compounds of general formula (VI) wherein A has the meaning indicated above, by reaction with (C, -C 4) -alkyl- or -phenylsulfonyl chlorides, in inert solvents and in the presence of a base, in the corresponding compounds of general formula (IV) wherein A and R37 have the meaning indicated above, the azides of general formula (VII) being then obtained with sodium azide in inert solvents. wherein A has the meaning indicated above, in another step, by transformation with (C, -C4-0) 3-P or PPh3, preferably (CH30) 3P, in inert solvents, is transformed into the amines. As a solvent, ordinary solvents which do not change under the reaction conditions are suitable depending on the individual process steps. These preferably include alcohols such as methanol, ethanol, propanol or isopropanol, or ethers such as diethyl ether, dioxane, 1,2-dimethoxyethane, tetrahydrofuran, glycoli ethyl ether or t-butyl methyl ether, or ketones such as acetone or butanone, or amides such as dimethylformamide or hexamethylphosphoric acid triamide, or hydrocarbons such as hexane, benzene, dichlorobenzene, xylene or toluene, or dimethylsulfoxide, acetonitrile, ethyl acetate, or halogenated hydrocarbons such as methylene chloride, chloroform or carbon tetrachloride, or pyridine, picoline or N-methylpiperidine. Mixtures of the solvents mentioned can also be used. As bases, the inorganic or organic base bases are suitable, depending on the individual process steps. These preferably include alkali hydroxides such as, for example, sodium or potassium hydroxide, or alkali carbonates such as sodium or potassium carbonate, or alkali alcoholates, such as, for example, sodium or potassium methanolate, or sodium or potassium ethanolate, or organic amines such as ethyldiisopropylamine, triethylamine, picoline, pyridine or N-methylpiperidine, or amides such as sodium amide or lithium-diisopropylamide, or lithium-N-silylalkylamides such as, for example, lithium-N- (bis) triphenylsilylamide or alkyl lithium, such as n-butyl -lithium. The base is used in a proportion of 1 mol to 10 mol, preferably from 1 mol to 3 mol, based on 1 mol of the compounds of general formula (VI). All the transformations are carried out, in general, at normal, high or reduced pressure (for example, from 0.5 bar to 5 bar). In general, normal pressure is used. The reduction of the azides is carried out with (CH30) 3P and hydrochloric acid. The reduction is effected, in general, in a temperature range of -50QC to the respective boiling point of the solvent, preferably from -20AC to + 90ac. As a solvent, all inert organic solvents which do not change under the reaction conditions are suitable here. These preferably include alcohols such as methanol, ethanol, propanol or isopropanol, or ethers such as diethyl ether, dioxane, tetrahydrofuran, 1-methyl-1-di-1-ether, or diethylene glycol dimethyl ether or amides such as hexamethylphosphoric acid triamide or dimethylformamide, or acetic. It is also possible to use mixtures of the solvents mentioned. The compounds of general formulas (IV) and (VII) are new and can be obtained as described above. The compounds of general formula (VI) are, in part, novel and can be obtained [D] By converting compounds of general formulas (VIII) or (IX) AN = C = 0 (VIII) or A-CO-N3 (IX) in which A has the meaning indicated above, with lithium bromide / (C4H9) 3P (0) and epoxides of general formula (X) wherein Q represents (Cj-C6) acyloxy, in inert solvents, optionally in the presence of a base, leaving the free hydroxyl function by a typical saponification or by a typical transesterification, or [E] When converting compounds of general formula (XI) A-NH-C02-X (XI) in which A has the meaning indicated above, and X represents a typical protecting group, preferably benzyl, in inert solvents and in the presence of a base, for example alkylene-lithium or lithium-N-alkyl- or lithium-N-silylalkyl-amides, preferably N-butyl-lithium, with epoxides of general formula (X), or by first transforming compounds of general formula (IX) ), by dissociation of nitrogen in alcohols, in the compounds of general formula (Xla) A-NH-C02-Y (Xla) in which A has the meaning indicated above and Y represents (C2-C6) -alkyl or linear branched, preferably n-butyl, and transformed into a second step as described in (D), in inert solvents and in the presence of a base, preferably lithium-N-alkyl or lithium-N-silylalkyl-amides or n-butyl- lithium and epoxides of general formula (X) or (F) When converting compounds of general formula (XII) wherein A has the meaning indicated above, either directly with acids and diethyl carbonate, or by first obtaining, by transformation of the compounds of general formula (XII) with acids, the compounds of general formula (XIII) wherein A has the meaning indicated above, and then cyclizes in the presence of a coadjuvant agent, in inert solvents. As a solvent, ordinary solvents which do not change under the conditions of the process are suitable depending on the individual process steps. reaction. These preferably include alcohols such as methanol, ethanol, propanol or isopropanol, or ethers such as diethyl ether, dioxane, 1,2-dimethoxyethane, tetrahydrofuran, glycol dimethyl ether or t-butyl methyl ether, or ketones such as acetone or butanone, or amides such as dimethylformamide or triamide. of hexamethylphosphonic acid, or hydrocarbons such as hexane, benzene, dichlorobenzene, xylene or toluene, or dimethylsulfoxide, acetonitrile, ethyl acetate, or halogenated hydrocarbons such as methylene chloride, chloroform or carbon tetrachloride, or pyridine, picoline or N-methylpiperidine. Mixtures of the solvents mentioned can also be used. As bases, the inorganic or organic base bases are suitable, depending on the individual process steps. These preferably include alkali hydroxides such as, for example, sodium or potassium hydroxide, or alkali carbonates such as sodium or potassium carbonate, or alkali alcoholates, such as, for example, sodium or potassium methanolate, or sodium or potassium ethanolate, or organic amines such as ethyldiisopropylamine, triethylamine, picoline, pyridine or N-methylpiperidine, or amides such as sodium amide or lithium-diisopropylamide, or lithium-N-silylalkylamides such as, for example, lithium-N- (bis) triphenylsilylamide or alkyl lithium, such as n-butyl -lithium. The base is used in a proportion of 1 mol to 10 'mol, preferably from 1 mol to 3 mol, based on 1 mol of the compounds of general formulas (X) and (XI). All the transformations are carried out, in general, at normal, high or reduced pressure (for example, from 0.5 bar to 5 bar). In general, normal pressure is used. The process [D] is preferably carried out in xylene or dichlorobenzene, optionally in the presence of triethylamine, at reflux. The base-catalyzed transesterification is carried out with one of the alcohols indicated above, preferably methanol, in a temperature range from -ioac to + 402 C, preferably at room temperature. As the bases, sodium bicarbonate, sodium methanolate, hydrazine hydrate, potassium carbonate or cesium carbonate are generally suitable. Cesium carbonate is preferred. Process (E) is carried out in one of the ethers indicated above with alkyl lithium or lithium-N-silylamide compounds, such as, for example, n-butyllithium, lithium-diisopropylamide or lithium-bis-trimethylsilylamide, preferably in tetrahydrofuran. and lithium-bis-trimethylsilyl-amide or n-butyllithium, in a temperature range of -100 ° C to + 20 ° C, preferably -7 ° C to -4 ° C. For the process (F), the alcohols indicated above, in the case of the subsequent cyclisation, tetrahydrofuran are suitable for the 1st stage, preferably. Suitable bases for cyclization are, preferably, the lithium-N-silylalkyl compounds indicated above or n-butyllithium. Especially preferred is n-butyl lithium. The first stage of the reaction is carried out at the boiling temperature of the corresponding alcohol, the cyclization in a temperature range of -70 ° C to room temperature. Cyclization (F) is carried out in the presence of an adjuvant agent and / or in the presence of an acid. Suitable as acids are generally inorganic acids, such as, for example, hydrochloric acid or sulfuric acid, or organic carboxylic acids with 1-6 carbon atoms, optionally substituted by fluorine, chlorine and / or bromine, for example, acetic acid, trifluoroacetic acid, trichloroacetic acid or propionic acid, or sulfonic acids with (C, -C4) alkyl or aryl radicals such as, for example, methanesulfonic acid, ethanesulfonic acid, benzenesulfadic acid or toluenesulfonic acid. Hydrochloric acid is especially preferred. The acid is used in a proportion of 1 mol to 10 mol, preferably 1 mol to 2 mol, based on 1 mol of the compound of the general formula (XII). Suitable adjuvants are conventional reagents such as phosgene, carbonyldiimidazole or diethyl carbonate or trichloromethyl chloroformate. Preferred are carbonyldiimidazole, diethyl carbonate or trichloromethyl chloroformate. As a solvent, the halogenated hydrocarbons indicated above are suitable. Methylene chloride is preferred. The compounds of the general formula (IX) are known or can be obtained by customary methods. The compounds of general formula (XIII) are mostly new and can be obtained, for example, as described above. The compounds of general formula (VIII) are known in part or new and can then be obtained, for example, by converting the corresponding amines with trichloroethyl chloroformate into one of the solvents indicated above, preferably xylene, at the reflux temperature. The compounds of general formula (IX) are known in part or new and can then be obtained, for example, from the corresponding carboxylic acids, by converting well with isobutyl chloroformate / acetone, sodium azide / water or with diphenylphosphorylazide / tetrahydrofuran or with xylene or methylene chloride in the presence of one of the bases indicated above, preferably triethylamine, from-to room temperature. The compounds of the general formulas (XI) and (Xla) are - partially known or new and can be obtained either by nitrogen cleavage of the corresponding carboxylic acid azides and transformation with the corresponding alcohols or by transformation of the corresponding amines with esters of the chloroformic acid, preferably benzyl chloroformate in one of the solvents indicated above, preferably tetrahydrofuran or dioxane, in a temperature range from -ioac to 200 bc, preferably from oac to 150 ° C. The minimum inhibitory concentrations (MIC) were determined by the procedure of serial dilutions on Iso-Sensitest agar (Oxoid). For each tested substance, a series of agar plates containing, respectively, decreasing concentrations were prepared by double dilution of the active substance. The agar plates were inoculated with a Multipoint (Denley) inoculator.

For the inoculation, overnight cultures of the pathogenic germs were used, which were previously diluted in such a way that each inoculation point contained about 1? 4 colony-forming particles. The inoculated agar plates were incubated at 37 ° C and the germ growth was read after about 20 hours. The MIC value (μg / ml) gives the lowest concentration of active substance at which no growth was recognizable at first sight. MIC values (μg / ml): S ph. SUph. T SUph. SUph. E. coll I Klcbt. Ptdm. Bonn Ex. No. 133 48N 25701 9TV Neumann I 57 USA 11 0.5 0.5 0.25 0.25 > 64 > 64 > 64 12 0.5 > 64 > 64 > 64 13 0.25 0.25 0.25 < > 64 > 64 > 64 0.125 14 0.5 > 64 > 64 64 15 0.25 0.5 0.25 < > 64 > 64 > 64 0.125 20 0.25 0.25 0.25 < 64 > 64 > 64 0.125 23 0.25 0.5 0.5 0.25 > 64 > 64 > 64 26 < 0.125 0.25 0.25 < > 64 > 64 > 64 0.125 42 < 0.125 > 0.125 > 0.125 < 64 64 > 64 0.125 43 0.5 0.5 0.5 0.5 > 64 > 64 > 64 For rapid growth mycobacteria, the MIC determination was carried out based on the method described by Swenson of Bouillon microdilution (see JM Swenson, C. Thornberry, UA Silcox, Rapidly growing mycobacteria.) Testing of susceptibility to 34 antimicrobial agents by broth microdilution ("Rapidly growing mycobacteria Susceptibility test to 34 antimicrobial agents by microdilution of the culture broth") Antimicrobial Agents and Chemotherapy, volume 22, 186-192 (1982)). The brain-heart extract medium was different, with the addition of 0.1% by volume of Tween 80. The strains of mycobacteria used were acquired in the DSM (Dt. Sammlung von Mikroorganismen ("German Collection of Microorganisms"), Braunschweig ). They were incubated in a humid chamber at 37 ° C. The MIC values were read after 2-4 days, when the exempt controls of preparation had become cloudy due to growth. The CMI value is defined as the lowest preparation concentration that completely inhibits macroscopically observable growth.

CMI Values: Mycobacterium smegmatis Determination of MIC with Mycoplasma pneumoniae The Pl 1428 strain of Mycoplasma pneumoniae was incubated, under aerobic conditions, in a PPLO medium to which 1% glucose, 2.5% yeast extract, 20% horse serum (donor) had been added. horse serum) and 0.002% phenol red. The CMI determinations were carried out based on the liquid microdilution method, described by Ter Laak and colleagues (EA ter Laak, A. Pijpers, JH Noordergraaf, E. Schoevers, JHM Verheijden: Comparison of Methods for in Laboratory Testing of Susceptibility of Porcine Mycoplasma Species to Antimicrobial Agents ("Comparison of methods for the in vitro assay of susceptibility of porcine mycoplasma species to antimicrobial agents"), Antimicrobial Agents and Chemotherapy, vol 35, 228-233 (1991)) . At the start of the turn, from red to yellow, the color of the control medium free of preparation was added 10% by volume of Alamar blue. Incubation at 37 ° C lasted for about 10 hours and MIC was defined as the value of the smallest preparation concentration at which the medium remained blue.

The compounds according to the invention of general formula (I) show, with low toxicity, a broad antibacterial spectrum, especially against gram-positive bacteria, as well as against mycobacteria, Haemophilus Influenzae, anaerobic organisms, against rapidly growing mycobacteria. These properties make possible its use as an active chemotherapeutic substance in medicine and veterinary medicine. The compounds according to the invention are especially active against bacteria and microorganisms analogous to bacteria, such as mycoplasmas. That is why they are especially well suited in medicine and veterinary medicine for the prophylaxis and chemotherapy of local and systemic infections, which are caused by such pathogenic germs. The present invention includes pharmaceutical preparations which, together with non-toxic, inert, pharmaceutically suitable excipients, contain one or more compounds according to the invention or which are composed of one or more active substances according to the invention, as well as the process for obtaining these preparations. The active substance (s) can also be present in microencapsulated form, optionally in one or more of the excipients mentioned above. Therapeutically active compounds should be present in the pharmaceutical preparations indicated above in a concentration between about 0.1 and 99.5% by weight of the total mixture, preferably between 0.5 and 95% by weight , approximately. The pharmaceutical preparations indicated above may also contain, in addition to the compounds according to the invention, other pharmaceutically active substances. It has been found advantageous in general, both in medicine and also in veterinary medicine, to administer the active substance (s) according to the invention in total amounts of from about 0.5 to about 500 mg / kg of body weight every 24 hours, preferably from 5 to 100 mg / kg, optionally in the form of several individual doses, to achieve the desired results. An individual dose contains the active substance or substances according to the invention, preferably in amounts of from about 1 to about 80 mg / kg of body weight, in particular from 3 to 30 mg / kg. The compounds according to the invention can also be combined with other antibiotics, in order to achieve the broadening of the activity spectrum and an increase in activity. Annex to the experimental part List of eluent mixtures used for chromatography I Dichloromethane: methanol II Toluene: ethyl acetate III Acetonitrile: water IV Ethyl acetate V Petroleum ether: ethyl acetate VI CH2Cl2: MeOH: NH3 (?) VII CH2Cl2: MeOH Abbreviations: z Benzyloxycarbonyl Boc t-butoxycarbonyl DMF Dimethylformamide Ph Phenyl Me Methyl THF Tetrahydrofuran CDI Carbonyldiimidazole DCE Dichloroethane Unless indicated otherwise, the examples given below can be obtained according to or analogously to the indications of EP 694 543, EP 693 491, EP 694 544, EP 697 412 and EP 738 726. Starting compounds Example I 5-bromo-2-isocyanato-pyridine hydrochloride HCI To a stirred solution of 100 g (0.58 mol) of 2-amino-5-bromopyridine in 400 ml of 1,2-dichloroethane is added dropwise, at the boiling temperature, 78.0 ml (0, 64 mol) of trichloroethyl chloroformate. After the addition, the mixture is refluxed for 2 hours, then the mixture is allowed to cool to room temperature. The precipitate that originates is separated by filtration, washed well with 100 ml of 1,2-dichloroethane and dried under high vacuum over sodium hydroxide. 98.3 g (72%) of the title compound are obtained as a yellow solid. P. of f .: 248-254ac (desco p.). Rf = 0.23 (ethyl acetate). MS (El) m / z = 198 (M) +. Example II (5R) -3- (5-Bromo-pyridin-2-yl) -5-butyryloxy-methyl-oxazolidin-2-one A suspension of 2.17 g (25 mmol) of lithium bromide and 5.46 g. g (25 mmol) of tributylphosphine oxide in 73 ml of xylene was boiled for 1 hour in a water separator. To this is added dropwise, at the boiling temperature, a mixture of 58.5 ml (0.42 mol) of triethylamine and 66.6 g (0.42 mol) of (R) -glycidyl butyrate. Simultaneously, 98.2 g (0.42 mol) of the compound of Example I are added in portions over 20 minutes. After the addition is complete, it is stirred at reflux for a further 1 hour. Allow to cool to room temperature and evaporate the solvent in vacuo. After chromatography of the residue on 1 kg of silica gel (toluene: ethyl acetate 95: 5), 37.9 g (26%) of the title compound are obtained in the form of an oil. Rf »0.43 (toluene: ethyl acetate 4: 1). MS (FAB) m / z-343 (M + H) +. ? -NRM (250 MHz, D6-DMSO): d = 0.81 (t, J = 7 Hz, 3H, CÜ3CH2); 1.5 (m, 2H, CHjCJHjCHjCO); 2.29 (t, J »7 Hz, 2H, CH 3 CH 2 CO 2CO); 3.91 (dd, J-7 Hz, 10 Hz, 1H, trans H-4); 4.25 (dd, J • 9 Hz, 10 Hz, 1H, H-4 cis); 4.36 (m, 2H, CH20); 4.97 (m, 1H, H-5); 8.08 (d, J • 1 Hz, 2H, H-3,4-pyridyl); 8.50 (d, J = 1 Hz, H-6 pyridyl). Example III (5R) -3- (5-bromo-pyridin-2-yl) -5-hydroxymethyl-oxazolidin-2-one A solution of 19.6 g (57.3 mmol) of the compound of Example II in 125 ml of water-free methanol is mixed with 185 mg (0.57 mmol) of cesium carbonate and stirred at room temperature for 5 hours. . The solvent is evaporated in vacuo and the residue is stirred with 30 ml of ether. The precipitate is separated by filtration, washed with 25 ml of water and 5 ml of ether and dried under high vacuum. 10.73 g (69%) of the title compound are obtained in the form of yellow crystals. Rf -0.09 (toluene: ethyl acetate 4: 1). MS (DCI, NH3) m / z-273 (M + H) +. 'H-NMR (200 MHz, CD30D): S = 3.68 (d, J-5.9 Hz, 1H, CH20); 3.87 (dd, J = 4.9 HZ, 1H, CH20); 4.06 (dd, J-7.10 Hz, 1H, trans H-4); 4.26 (dd, J-9.10 Hz, 1H, H-4 cis); 4.75 (m, 1H, H-5); 7.92 (dd, J-1.5 Hz, 10 Hz, 1H, H-3 pyridyl); 8.12 (d, J-10 Hz, 1H, H-4 pyridyl); 8.40 (d, J-1.5 Hz, 1H, H-6 pyridyl).

Example IV 5- (2-pyridyl) -thiophene-2-carbonylazide g (97.45 mmol) of 5- (2-pyridyl) -thiophene-2-carboxylic acid are dissolved in 200 ml of acetone, mixed with 15.94 ml (115 mmol) of Et 3 N and cooled to 0 ° C. To the reaction solution thus obtained, a solution of 14.85 ml (115 mmol) of isobutyl chloroformate in 88 ml of acetone is slowly added dropwise with stirring. After 1 hour at 0 ° C a solution of 9.5 g (146 mmol) of sodium azide in 44 ml of water is added dropwise, the mixture is then stirred for 1 hour at 0 ° C and allowed to reach room temperature. The reaction mixture is poured into ice water and filtered under vacuum and further processed. Yield: 21 g of wet powder. Example V 5- (2-pyridyl) -butyloxycarbonylamino-thiophene Over 400 ml of boiling n-butanol, 21 g of the compound of example IV are added in portions. After cessation of gas evolution, it is stirred at reflux for 15 minutes. After cooling to room temperature it is concentrated, the residue is stirred with ether, filtered in vacuo and dried at 50 ° C. in a drying cabinet with air circulation. Yield: 18.8 g (75% of theory). 'H-NMR (200 MHZ, D6-DMS0): δ-10.8 (s, 1H); 8.45 (d, J-5 Hz, 1H); 7.68-7.85 (m, 2H); 7.5 (d, J-5 Hz, 1H); 7.1-7.2 (m, 1H); 6.57 (d, J-5 Hz, 1H); 4.14 (t, J = 7 Hz, 2H); 1.62 (q, J-7 Hz, 2H); 1.39 (h, J-7 Hz, 2H); 0.92 (t, J «7 Hz, 3H). Example VI (5R) -3- (5- (2-pyridyl) -thien-2-yl) -5-hydroxymethyl-oxazolidin-2-one 18.8 g (68 mmol) of the compound of Example V are dissolved in 190 ml of absolute THF, mixed with 10 mg of 1,10-phenanthroline hydrate and cooled to -70 ° C. Then, approximately 27 ml of 2.5 N solution of n-butyl lithium in hexane are added slowly, dropwise until the color changes to red. Then 9.6 ml (68 mmol) of (R) -glycidyl butyrate are added dropwise. Allow to reach room temperature, mix with saturated ammonium chloride solution, separate the organic phase and extract the aqueous phase twice with methylene chloride. The combined organic phases are dried (S04Na2) and concentrated. The residue is stirred with ether and filtered in vacuo. Yield: 15.3 g (81.5% of theory). Rf -0.06 (CH2C12: CH30H = 100: 3). P. of f. : 19iac. ? -NRM (200 MHZ, D6-DMSO): S-8.45 (d, J-5 Hz, 1H); 7.7-7.9 (m, 2H); 7.6 (d, J-5 Hz, 1H); 7.15-7.25 (m, 1H); 6.58 (d, J-5 Hz, 1H); 5.28 (t, J = 7 Hz, 1H); 4.77-4.9 (m, 1H); 4.13 (dd, J-10 Hz, 9 Hz, 1H); 3.86 (dd, J-10 Hz, 6 HZ, 1H); 3.55-3.78 (m, 2H). Example VII 6- (benzyloxycarbonylamino) -3-methyl-2-benzothiazolinone To the mixture dropwise, to oac, 1.76 g (8.12 mmol) of 6-amino-3-methyl-2 (3i) -benzothiazolone hydrochloride in 17 ml of water, 14 ml of THF and 17 ml of solution are mixed. saturated NaHCO3 with 1.3 ml (9.10 mmol) of benzyl chloroformate. After 1 hour, add 120 ml of water, evaporate the THF in vacuo, filter the precipitate in vacuo, wash three times with water, twice with petroleum ether and dry at 60 ° C. Yield: 2.44 g (96%). P. of f. : 183SC. Rf (II, 7: 3) «0.39. ? -NMR ([D6] DMSO): S-7.77 (d, J = 1 Hz, 1H, 7-H benzothiazolinone); 7.23-7.45 (m, 6H, Ph); 7.22 (d, J = 6 Hz, 1H, 4-H benzothiazolinone); 5.15 (s, 2H); 3.38 (s, 3H-CH3). EXAMPLE VIII (5R) -3- [3-Methyl-2-benzothiazolinon-6-yl] -5-hydroxymethyl-oxazolidin-2-one The 26.76 g (85.12 mmol) of the compound of Example VII are dissolved in 400 ml of THF, mixed with 10 mg of 1,10-phenanthroline hydrate and cooled to -70 ° C. Then, 34 ml of a 2.5 N solution of n-butyllithium in hexane are slowly added dropwise until the color changes to red.

Then 12 ml (85.12 mmol) of (R) -glycidyl butyrate are added dropwise. The TA is allowed to reach, mixed with saturated ammonium chloride solution and the THF evaporated in vacuo. The resulting precipitate is filtered under vacuum, washed with water and with ether and dried under high vacuum. Yield: 17.93 g (75%). P. of f .: 166ac. Rf (II, 1: 1) = 0.09. 'H-NMR ([D6] DMSO): S-7.80 (d, J-1 HZ, 1H, 7-H benzothiazolinone); 7.60 (dd, J = 6, J "1 Hz, 1H, 5-H benzothiazolinone); 7.32 (d, J = 6 Hz, 1H, 4-H benzothiazolinone); 5.23 (t, J = 6 Hz, 1H, OH); 4.62-4.80 (m, 1H, 5-H); ); 4.10 (t, J-9 Hz, 1H, 4-H); 3.85 (dd, J = 9, J = 5 HZ, 1H, 4-H); 3.48-3.75 (m, 2H, CH20); 3.40 (S, 3H, CH3). Method B 9.3 g (0.03 mol) of the compound of Example VII are dissolved in 150 ml of THF and cooled to -70 ° C. Then 4 ml (0.01 mol) of 2.5M solution of n-butyllithium in hexane are added dropwise. After this, another 8 ml (0.02 mol) of n-butyllithium and 4.23 ml (0.03 mol) of (R) -glycidyl butyrate are slowly added dropwise simultaneously. It is allowed to reach room temperature and is then stirred for three hours. The processing is carried out as described for method A. Yield: 6 g (72%). Analogously to the recipes of Examples I to VIII, the compounds indicated in Table I are synthesized: Table I Table I (continued) EXAMPLE XXIII (5R) -3- (5-bromo-pyridin-2-yl) -5-methanesulfonyloxy-methyl-oxazolidin-2-one A solution of 10.5 g (38.44 mmol) of the compound of Example III and 6.40 ml (46.14 mmol) of triethylamine in 36 ml of water-free dichloromethane, cooled to 0 c, is slowly mixed with 3, 27 ml (42.28 mmol) of methanesulfonyl chloride. It is then stirred for 10 minutes at 0-5 and the mixture is stirred with 50 ml of ice water. The organic phase is separated, washed with 20 ml of saturated NaHCO3 solution and 20 ml of ice water and dried over S04Mg. The solvent is evaporated in vacuo and the residue is stirred with 50 ml of ether, filtered in vacuo and dried under high vacuum. 12.8 g (95%) of the title compound are obtained in the form of colorless crystals. P. of f. : 138-138, 5ac. Rf = 0.65 (dichloromethane: methanol 95: 5). MS (DCI, NH3) m / z = 351 (M + H) +. H-NMR (250 MHZ, D6-DMS0): δ-3.25 (S, 3H, OS02CH3); 3.91 (dd, J = 7.10 Hz, 1H, trans H-4); 4.27 (dd, J-10.10 Hz, 1H, H-4 cis); 4.52 (m, 2H, CH20); 5.02 (m, 1H, H-5); 8.09 (s, 2H, H-3,4 pyridyl); 8.52 (s, 1H, H-6 pyridyl). EXAMPLE XXIV (5R) -3- (5-Bromo-pyridin-2-yl) -5-azidomethyl-oxazolidin-2-one A stirred solution of 12.5 g (35.6 mmol) of the compound of Example XXIII in 48 ml of DMF free of water is mixed with 3.01 g (46.28 mmol) of sodium azide and stirred at 7oac for 3 hours. Allow to cool to room temperature and stir with 100 ml of ice water. The precipitate that originates is separated by filtration, washed with 50 ml of water and 20 ml of petroleum ether and dried in air. 10.1 g (95%) of the title compound are obtained in clear crystals form. P. of f. : 64-67BC.

Rf = 0.63 (toluene: ethyl acetate 2: 3). MS (DCI, NH3) m / Z = 298 (M + H) +. 'H-NMR (250 MHZ, D6-DMSO): < 5"3.73 (m, 2H, CH2N3); 3.87 (dd, J = 6.8 Hz, 1H, trans H-4); 4.22 (dd, J = 8.8 Hz, 1H, H-4 cis); 4.92 (m, 1H, H-5); 8.08 (S, 2H, H-3, 4-pyridyl); 8.51 (s, 1H, H-6 pyridyl). Example XXV (5S) -3- (5-bromo-pyridin-2-yl) -5-aminomethyl-oxazolidin-2-one hydrochloride A stirred solution of 10.1 g (33.9 mmol) of the compound of Example XXIV in 16.5 ml of 1,2-dimethoxyethane is heated to 50ac. 4.68 ml (4.70 mmol) of trimethyl phosphite (gas evolution) are slowly added dropwise, and after the addition is complete, it is stirred at 90 ° C. for 2 hours. 6.6 ml of 6H-CH2 are then added dropwise and the mixture is again stirred at 90 ° C. for a further 2 hours. It is allowed to cool to room temperature, the precipitate is separated by filtration, washed with 2 x 10 ml of 1,2-dimethoxyethane and dried under high vacuum over NaOH. 8.9 g (85%) of the title compound are obtained in the form of colorless crystals. P. of f. : 260-262BC.

Rf = 0.53 (acetonitrile: water 4: 1). MS (El) m / z = 271 (M) +. ? -NMR (250 MHZ, D6-DMSO): λ = 3.28 (m, 2H, C_H? NH7); 3.93 (dd, J = 7.9 Hz, 1H, trans H-4); 4.28 (dd, J-9.9 Hz, 1H, H-4 cis); 5.00 (m, 1H, H-5); 8.05 (s, 2H, H-3, 4-pyridyl); 8.5 (m, 3H, NH2, H-6 pyridyl). EXAMPLE XXVI (5S) -3- (5-Bromo-pyridin-2-yl) -5- ((t-butyloxy) carbonyl) -aminomethyl-oxazolidin-2-one B 4.7 g (15 mmol) of the compound of Example XXV are suspended in 100 ml of CH2C12. Then 2.2 ml (16 mmol) of triethylamine are added, resulting in a solution. It cools to oac. Then 3.5 g (16 mmol) of Boc anhydride are added so that the temperature does not exceed + 5 ° c and is left overnight, stirring, at room temperature. The organic phase is washed with saturated NaCl solution, dried over S04Mg and concentrated. 5.4 g (97% of theory) of the product are obtained in the form of a white solid. P. of f. : 184ac. Rf value (petroleum ether: ethyl acetate 10: 4) = 0.30.

Example XXVII ((5S) -3- (5- [3-pyridyl] -pyridin-2-yl) -5- ((t-butyloxy) -carbonyl) aminomethyl-oxazolidin-2-one .3 g (14.24 mmol) of the compound of Example XXVI and 2.81 g of diethyl- (3-pyridyl) borane are placed in 100 ml of absolute THF., in an argon atmosphere. A solution of 0.5 g (0.43 mmol) of ((PPh3) 4Pd) in 90 ml of THF and 4.9 ml (9.83 mmol) of 2M sodium carbonate solution is added. The mixture is stirred under reflux for 5 days. After cooling to RT, 10 g of diatomaceous earth are added and concentrated. The residue is applied to a column filled with silica gel and eluted with ethyl acetate. 4 g (76% of theory) of the title compound are obtained. P. of f .: 163ßc. Value f -0.36 (CH2Cl2: Me0H 100: 5).

Example XXVIII (5S) -3- (5- [3-pyridyl] -pyridin-2-yl) -5-aminomethyl-oxazolidin-2-one trichlorohydrate 3.8 g (10.3 mmol) of the compound of example XXVII are suspended in 25 ml of dioxane. 32.1 ml of a 4M solution of C1H in dioxane are added and left overnight, with stirring, at room temperature. The residue is concentrated and the residue is stirred with ether. The solid substance is then filtered under vacuum through a fritted glass filter and then washed with ether. Dry in high vacuum and obtain 3.7 g (95% of theory) of the title compound. P. of f. : > 250ßc MS (El) m / z-271 (M +), 172.? -NMR (200 MHz, DMSO-dβ): d-9.35 (s, 1H); 8.93 (m, 3H); 8.6 (width, 3H); 8.42 (dd, J-9, J-3, 1H); 8.24 (d, J-9, 1H); 8.11 (dd, J-7.5, J «6.5, 1H); 6.7-5.3 (width, 2H); 5.06 (m, 1H); 4.38 (tr, J-10, 1H); 4.03 (dd, J-10, J-7.5, 1H); 3.29 (m, 2H). Analogously to the recipes of examples XXIII to XXVIII, the compounds indicated in Table II were synthesized: Table II Table II (continued): E-Temolo XLV (5S) -3- (3-isopropyl-2-benzoxazolinon-6-yl) -5-aminomethyl-2-oxazolidinone hydrochloride Analogously to the recipe of Example IV, starting from 3-benzyloxy-4-nitro-benzoic acid, the corresponding azide is synthesized (quantitative yield). Analogously to the recipe of Example V, from the 3- benzyloxy-4-nitro-benzoylazide the corresponding butylcarbamate is synthesized (yield: 63%, R, (VII, 95: 5) = 0.51). The 3-benzyloxy-l-butoxycarbonylamino-4-nitrobenzene is converted, analogously to the recipe of Example VI, into the corresponding oxazolidinone (yield: 73%, Rf (II, 1: 4) = 0.24). Analogously to the recipes of examples XXIII a XXVIII, starting from (5R) -3- (3-benzyloxy-4-nitrophenyl) -5-hydroxymethyl-3-oxazolidinone, the corresponding amine is synthesized (yields: 92%, 92% or 83%, Rf (VIII , 85: 10: 5) = 0.08). A mixture of (5S) -3- (3-benzyloxy-4-nitrophenyl) -5-aminomethyl-2-oxazolidinone (20.6 g, 0.06 mol) and di-t-butyl dicarbonate (14.4 g , 0.066 mol) in dichloromethane (300 ml), stirred at oac for 14 hours. The reaction mixture is concentrated and the product is precipitated with petroleum ether (yield: 25.4 g (95%), Rf (I, 10: 1) = 0.80). It is stirred under a hydrogen atmosphere (1 atm) for 14 hours (5S) -3- (benzyloxy-4-nitrophenyl) -5- (t-butoxycarbonyl-aminoethyl) -2-oxazolidinone (25.3 g, 0.057 mol) in Ethanol / THF (2: 3, 500 ml), with Pd / C (10%, 0.5 g). The catalyst is then filtered and the solvent is evaporated (yield: 18.9 g (quantitative), Rf (I, 10: 1) - 0.28). To a mixture of (5S) -3- (4-amino-3-hydroxyphenyl) -5- (t-butoxycarbonylaminomethyl) -2-oxazolidinone (18.9 g, 0.058 mol), acetone (8.6 ml, 0.116 mol) ) and THF (500 ml) is added, to oac, borane-tetrahydrofuran complex (64 ml, 64 mmol) and stirred at room temperature for another 24 hours. The solution is mixed with IVM sodium hydroxide (58 ml, 58 mmol), dried (S04Na2) and the solvent evaporated in vacuo (yield: 16.1 g (quantitative), Rf (I, 10: 1) -0, 53). A solution of (5S) -3- (4-isopropylamino-3-hydroxy-phenyl) -5- (t-butoxycarbonylaminomethyl) -2-oxazolidinone (8.8 g, 24 mmol) and carbonyldiimidazole (CDI, 4.1 g 25.2 g) in DMF (200 ml) is stirred at room temperature for 4 hours.The mixture is poured into ice water and the precipitate that is deposited is filtered in vacuo (yield: 9.0 g (96%). ), R, (I, 10: 1) = 0.71) A suspension of (5S) -3- (isopropyl-2-benzothiazolinon-6-yl) -5- (t-butoxycarbonylaminomethyl) -2-oxazolidinone ( 9.0 g, 23 mmol) and dioxane (200 ml) is mixed with 4M-C1H (in dioxane, 72 rol, 287 mmol) and stirred at room temperature for 14 hours The precipitate that is deposited is filtered under vacuum, Wash with ether (2 times) and dry Yield: 7.4 g (99%) .MS (Cl, NH3) m / z = 309 (M-C1 + NH4 +). 'H-NMR (200 MHZ, [ D6] DMSO): * * 8.5 (bs, 3H, NH3C1); 7.62 (d, 1H, Ar-H); 7.45 (d, 1H, Ar-H); 7.25 (dd, 1H, Ar-H); .00 (m, 1H, 5-H); 4.45 (m, 1H, HCMe2); 4.31 (t, 1H, 4-H); 3.90 (dd, 1H, 4-H); 3.20 (d, 2H, CH2N); 1.45 (d, 6H, CH3).

Use XLVI (5S) -3- (3-isopropyl-2-benzyloxazolinon-6-yl) -5- (benzyloxy-acetylaminomethyl) -2-oxazolidinone Analogously to the recipe of Example 3, the title compound is synthesized from the corresponding hydrochloride (example XLV) and benzyloxyacetyl chloride. Yield: 93%. Rf (I, 10: 1) - 0.69. Preparation Examples Example 1 (5S) -3- (5- [3-pyridyl] -pyridin-2-yl) -5- (2-nitro-prop-l-en-l-yl-aminomethyl) -oxazolidin-2 -one Under an argon atmosphere, 100 mg (0.37 mmol) of the compound of example XXVIII (free base, obtained by dissolving in water, adding aqueous NH.sub.2 to pH ll, extracting with CH2C12, drying over S04Mg and concentrating are dissolved. ) in 1 ml of DMF and 200 mg (1.11 mmol) of 2- (2-nitro-prop-1-en-1-yl-amino) -pyridine are added and the mixture is stirred overnight. It is mixed with water, extracted 3 times with ethyl acetate, the organic phase is washed with saturated solution of CINa and dried over S0Mg. Concentrate and purify by column chromatography on silica gel (eluent CH2Cl2: MeOH 100: 5). 126 mg (96% of theory) of the title compound are obtained. P. of f. : 207ac. Rf value (CH2Cl2: MeOH 10: 1) - 0.57. MS (DCI): 356 (M + H) +. 'H-NMR (200 MHZ, DMS0-d6): d-8.95 (d, J-2, 1H); 8.79 (d, J-2, 1H); 8.60 (dd, J = 5, J-2, 1H); 8.4-7.9 and 7.6-7.4 (m, total 6H); 4.9 (m, 1H); 4.3 (m, 1H); 4.05 (m, 1H); 3.7 (m, 2H); 1.95 and 1.93 (s, 3H total). Example 2 (5R) -3- (2-Methyl-benzo [4,5-d] thiazol-6-yl) -5- (2-thiazolyl-aminomethyl) -oxazolidin-2-one In an argon atmosphere, 292 mg (2.92 mrool) of 2-aminothiazole are placed in 5 ml of absolute THF and, at -78 [deg.] C., mixed with 1.33 ml (2.92 mmol) of 2.2 M solution. of n-butyl-lithium. Stir at -78ac for 30 minutes. 0.5 g (1.46 mmol) of (5R) -3- (2-methyl-benzo [4,5-d] thiazol-6-yl) -5-methoxysulfonyloxymethyl-oxazolidin-2-one dissolved in 5 ml of absolute THF and stir at -78ac for 1 hour. The cooling bath is separated and stirred overnight. Add C1NH4 solution and C1H solution (to pH 3), extract with chloroform, dry over S04Mg and concentrate. The substance is purified by column chromatography over silica gel (eluent CH2Cl2: MeOH 100: 1 to 100: 3). 193 mg (38% of theory) of the title compound are obtained. P. of f .: 207ßc. Rf »0.47 (CH2Cl2: MeOH 10: 1). Example 3 (5R) -3- (5- (2-pyridyl) -thien-2-yl) -5-thioacetylaminomethyl-oxazolidin-2-one 3.48 mg (1 mmol) of the compound of the example are mixed.

XXIX with 4 ml of THF and 0.24 ml (1.7 mmol) of triethylamine.

To the reaction mixture thus obtained is added, with stirring, 152 μl (1.1 mmol) of ethyl dithioacetate and is kept at room temperature for 24 hours. After concentrating, chromatography on silica gel with methylene chloride / methanol (100: 2). Yield: 100 mg (36% of theory). P. of f .: 18iac (decomp.). Rf -0.36 (I, 100: 5). 'H-NMR (D6-DMSO, 300 MHZ): or * «10, 37 (br, 1H); 8.47 (d, J = 5 Hz, 1H); 7.75-7.88 (m, 2H); 7.62 (d, J-5 Hz, 1H); 7.2 (m, 1H); 6.58 (d, J - *** • 5 Hz, 1H); 5.03-5.13 (m, 1H); 4.21 (dd, J-10 HZ, 9 Hz, 1H); 3.95 (t, J = 6 Hz, 2H); 3.85 (dd, J-10 HZ, 6 Hz, 1H); 2.45 (s, 3H). Analogously to the recipes of Examples 1 to 3, the compounds indicated in Table 1 are synthesized: Table 1 Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued) Table 1 (continued) Example 63 (5S) -3- (3-isopropyl-2-benzoxazolinon-6-yl) -5-hydroxyacetylamino-methyl-2-oxazolidinone The compound of Example XLVI (390 mg, 0.89 mmol) in THF (10 mL) and ethyl acetate (10 mL) is stirred with Pd (OH) 2 / C (5%, 30 mg) under a hydrogen atmosphere. to 3 bars. The catalyst is filtered, the residue is washed with THF, the filtrate is concentrated and stirred with dichloromethane. 36 mg (11%) of the title compound are obtained as a white solid. Yield: 11%. Value fi (I, 10: 1) = 0.23. MS (Cl) = 367 (M + NH 4 +). ? -NMR (200 MHz, [D6] DMSO): d = 10, 37 (bt, 1H); 7.62 (dd, 1H) / 7.43 (d, 1H); 7.23 (dd, 1H); 5.60 (t, 1H, OH); 4.75 (m, 1H); 4.50 (m, 1H); 4.20 (t, 1H); 3.80 (, 3H); 3.50 (m, 2H); 1.50 (d, 6H). It is noted that, in relation to this date, the best method known to the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims (1)

CLAIMS 1. Substituted oxazolidinones of the general formula (I) characterized in that A represents a 5-membered aromatic heterocycle attached directly through a carbon atom, with up to 3 heteroatoms of the group S, N and / or O, which may further possess a benzyl or condensed naphthyl ring, or represents an aromatic heterocycle with a nitrogen atom, at least, of 6 links, directly attached through a carbon atom, or represents a bi- or tricyclic aromatic residue, each of 6 links, attached directly through an atom of carbon, with at least one ring containing nitrogen, or represents ß-carbolin-3-yl or indolizinyl linked directly through the 6-membered ring, the rings being, if appropriate, respectively up to trisubstituted by identical substituents or various carboxy, halogen, cyano, mercapto, formyl, phenyl, trifluoromethyl, nitro, alkoxy, alkoxycarbonyl, alkylthio or acyl, linear or branched, with up to 6 carbon atoms respectively, or or linear or branched alkyl or alkenyl with up to 6 carbon atoms respectively, which, in turn, can be substituted by phenyl, and / or are substituted by pyridyl which, in turn, can be substituted by linear or branched alkyl or alkoxy with up to 6 10 carbon atoms respectively, or represents a remainder of the formula Wherein R3, R4, R5, R6 and R7 are the same or different and mean hydrogen or carboxy, halogen, cyano, formyl, trifluoromethyl, nitro, linear or branched alkyl with up to 6 carbon atoms or a group of formula wherein R13 and R14 are the same or different and mean hydrogen, linear or branched alkyl with up to 4 carbon atoms or phenyl, R2, R8, R9, R10, R "and R12 are the same or different and mean hydrogen, cycloalkylcarbonyl or cycloalkyl with 3 a 6 carbon atoms respectively, or alkoxycarbonyl or Alkylthio, linear or branched, with up to 6 carbon atoms respectively, or means straight or branched alkyl with up to 10 carbon atoms which, if appropriate, is substituted by cyano, trifluoromethyl, halogen, phenyl, hydroxyl, carboxyl, alkoxycarbonyl linear or branched with up to 6 carbon atoms, aryl with 6 to 10 carbon atoms, cycloalkyl with 3 to 6 carbon atoms and / or a group of formula R17-N-S02-Rlg, Rl9R20-N-SO2- OR R21-s (?) D, wherein c means a number 0 or 1, R15, R16 and R17 have the meaning indicated above for R13 and R14 and are the same or different from these, or form, together with the atom of nitrogen, a saturated heterocycle of 5 to 6 links, if necessary with another The heteroatom of the series N, S and / or O which, if appropriate, can also be substituted on another nitrogen atom by linear or branched alkyl or acyl with up to 3 carbon atoms, R19 and R20 have the meaning indicated above for R13 and R14 and are the same or different from these, d means a number 0, 1 or 2, R and R21 are the same or different and mean straight or branched alkyl with up to 4 carbon atoms, benzyl, phenyl or tolyl, or 25 means straight or branched acyl with up to 6 carbon atoms which, if appropriate, is substituted by trifluoromethyl, trichloromethyl or by a group of formula -OR22, wherein R22 means hydrogen or linear or branched alkyl with up to 6 carbon atoms which, if appropriate, is substituted by aryl with up to 10 carbon atoms, or means a group of formula - (CO) e-NR * ° R24, where e has the meaning indicated above for cy is same or different from this e, R23 and R24 and R23 have, respectively, the meaning indicated above for R15, R16 and R17 and are the same or different from these, R27 and R28 have the meaning indicated above for R13 and R14 and are the same or 20 different to these, f has the meaning indicated above for dy and is the same or different from it, R26 and R29 have respectively the The meaning indicated above for R and R21 and are the same or different from these, D means an oxygen atom or a residue of the formula -S (0) f, wherein 5 g means a number 0, 1 or 2, E and L are the same or different and mean an oxygen atom or one of sulfur, G, M, T and are the same or different and mean an oxygen atom or a sulfur atom or a group of formula -NR30, wherein R30 means hydrogen or linear or branched alkyl with up to 5 carbon atoms, 15 a and b are the same or different and represent a number 1 6 2, R 1 represents a radical of formula • C- 31 • C- C- (CHA-O-R 34 II II, 32 II 2 h S. NR ", or 20 wherein R31 means linear or branched alkyl with up to 7 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, phenyl or a group of formula -NR38R39, wherein R38 and R39 have the meaning indicated above for R13 and R14 and are the same or different from these, > 32 means hydrogen, cyano, cycloalkyl with 3 to 6 carbon atoms, phenyl or linear or branched alkyl with up to 7 10 carbon atoms, R33 means hydrogen, linear or branched alkyl with up to 7 carbon atoms, phenyl, cycloalkyl with 3 to 6 carbon atoms or a group of formula -NR * ° R * 1, 15 where R4o and R4i have the meaning indicated above for R13 and R14 and are the same or different from these, h means a number 1, 2, 3 or 4, R34 means hydrogen, straight or branched alkyl with up to 6 carbon atoms or benzyl, R35 and R36 they are the same or different and denote hydrogen or linear or branched alkyl with 25 to 6 carbon atoms, or R1 represents cyano or represents a saturated, partially unsaturated or unsaturated heterocycle of 5-7 links with up to 3 heteroatoms of the group S, N and / or that, if appropriate, is also substituted by a N-function with identical or different substituents benzyl, halogen or by linear or branched alkyl with up to 5-carbon atoms, and their stereoisomers, mixtures of stereoisomers eros and salts. Compounds of the general formula (I), according to claim 1, characterized in that A represents quinolyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, pyridyl, pyridazyl or thienyl linked respectively through a carbon atom which, given the case, are up to three-substituted by identical or different substituents fluoro, chloro, bromo, phenyl or by alkyl or alkylthio, linear or branched, with up to 4 carbon atoms respectively, or by linear or branched alkenyl with up to 4 carbon atoms which, in turn, may be substituted by phenyl, and / or are substituted by pyridyl which, in turn, can be substituted by linear or branched alkyl or alkoxy with up to 5 carbon atoms respectively, or represents a radical of formula where G means an oxygen or sulfur atom, 10 L means an oxygen or sulfur atom, R8 means linear or branched alkyl or alkylthio with up to 6 carbon atoms respectively, R3, R4 and R5 are the same or different and mean Hydrogen, fluorine, chlorine or bromine, represents a radical of formula 31 33-C-R • C-R '-C- (CH,) h- O- R II "32 S NR32 O wherein R31 means straight or branched alkyl with up to 5 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or a group of formula -NR38R39, wherein R38 and R39 are the same or different and 5 means hydrogen, methyl or ethyl R32 means hydrogen, cyano, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl or straight or branched alkyl with up to 5 carbon atoms, R33 means hydrogen, straight or branched alkyl with up to 5 carbon atoms, phenyl, cyclopropyl, cyclobutyl, scyclopentyl, cyclohexyl or a group of formula -NR4 ^ 41, wherein R40 and R41 have the meaning indicated above for R38 and R39 and are the same or different from these, h means a number 1, 2, 3 or 4, R34 means hydrogen, linear or branched alkyl with up to 4 carbon atoms or benzyl, R35 and R36 are the same or different and mean hydrogen or linear or branched alkyl with 25 to 4 carbon atoms, Rl represents cyano or represents thienyl, oxazolyl, thiazolyl, isoxazolyl or pyrazolyl which, if appropriate, is also unsubstituted through a N-function by the same or different substituents benzyl, fluorine, chlorine, bromine or by linear or branched alkyl with up to 3 carbon atoms, and their stereoisomers, mixtures of stereoisomers and you go out. Compounds of the general formula (I), according to claim 1, characterized in that A represents quinolyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, pyridyl, pyridazyl or thienyl linked respectively through a carbon atom which, if appropriate, are up-substituted by identical or different substituents fluoro, chloro, bromo, phenyl, by alkyl or alkylthio, linear or branched, with up to 3 carbon atoms respectively, or by linear or branched alkenyl with up to 3 carbon atoms which, in turn, may be substituted by phenyl, and / or substituted by pyridyl which, in turn, can be substituted by linear or branched alkyl or alkoxy with up to 4 carbon atoms respectively, or represents a radical of formula wherein G means an oxygen or sulfur atom, L means an oxygen or sulfur atom, R8 means linear or branched alkyl with up to 4 carbon atoms, R3, R4 and R5 are the same or different and mean hydrogen, fluorine, chlorine or bromine, represents a radical of formula where > 31 means straight or branched alkyl with up to 4 carbon atoms, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 25 phenyl or a group of formula -NR38R39, wherein R38 and R39 are identical or different and denote hydrogen or methyl, R32 is hydrogen, cyano, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo, phenyl or linear or branched alkyl having up to 4 carbon atoms carbon, R33 is hydrogen, linear or branched alkyl having up to 4 carbon atoms, phenyl, cyclopropyl, cyclobutyl, cyclopentyl, ciciohexilo or a group of formula -NR4 ^ 41 wherein R40 and R41 are as defined above for R38 and R39 and are identical or different to these, h denotes a number 1, 2, 3 6 4, R34 is hydrogen, linear or branched alkyl having up to 3 carbon atoms or benzyl, R3j and R36 are identical or different and are hydrogen or alkyl linear or branched with up to 3 carbon atoms, or R1 represents cyano or represents thienyl, thiazolyl, isoxazolyl or pyrazolyl which, if appropriate, can also be up to aubstituted by a N-function by the same or different substituents benzyl, fluorine, chlorine, bromine or by linear or branched alkyl with up to 3 carbon atoms, and their stereoisomers, mixtures of stereoisomers and salts. Compounds of general formula (I), according to claim 1, chosen from the group consisting of Process for the production of the compounds of general formula (I), according to claim 1, characterized in that they are transformed: [A] Compounds of general formula (II) wherein A has the meaning indicated above, with compounds of general formula (III) R'-Y (III) in which R1 has the meaning indicated in claim 1, and Y represents, depending on R1, hydrogen, halogen or represents linear or branched C, -C4 alkoxy or oxyalkoxycarbonyl, or [B] Compounds of general formula (IV) wherein A has the meaning indicated above, R37 represents (C, -C4) alkyl, with compounds of general formula (V) NH2-Rr (V) in which R1 'represents one of the heterocycles indicated above as R1 or with ethyl dithioacetate in inert solvents, if appropriate in the presence of a base, in the case of the S-oxides is carried out an oxidation following usual methods, if required, they are introduced or other substituents are derived or functional groups already present by conventional methods, if appropriate, the compounds are converted to the salts, in known manner, or the compounds of their salts are dissociated, and, if appropriate, the stereoisomers are separated according to customary methods. Compounds of general formula (I), according to claim 1, for use in the fight against diseases. Use of compounds of general formula (I), according to claim 1, for the production of medicaments. Medicaments, characterized in that they contain compounds of general formula (I), according to claim

1. REflUMS OF THE INVENTION The present invention relates to new substituted oxazolidinones, of general formula (I) wherein the substituents have the meaning indicated in the description, process for their manufacture and their use as a medicament, especially as an antibacterial medicament.