MXPA98000157A - New derivatives of oxazolidinone, processes to prepare the same and medicines that contain these compues - Google Patents

Abstract

The invention relates to novel oxazolidinone derivatives, processes for their production as well as pharmaceutical agents containing the substances. The present invention relates to compounds of general formula I (See Formula) which symbols have the meanings as listed in the claims.

Description

NEW DERIVATIVES OF OXAZOLIDININE. PROCESSES TO PREPARE THE SAME AND MEDICINES THAT CONTAIN THESE COMPOUNDS.

FIELD OF THE INVENTION It is known that the compounds which carry an acidic and basic group that is capable of inhibiting the aggregation of blood platelets when this is a certain distance between the acidic and basic group in the compounds (drugs of the future 19 (2): 135 -159 (1994) Compounds with anti-aggregation action in blood platelets that have been described in the specifications of patent WO 93/14077, EP-A-0 537/980, EP-A-0 542 363, WO 94/22834, WO 94/22835 and EP 0623615A1.

BACKGROUND OF THE INVENTION The present invention relates to novel oxazolidinone derivatives, processes for the production thereof as well as pharmaceutical agents containing these substances.

REF: 26451 It has now been established that oxazolidinone derivatives effectively inhibit the aggregation of blood platelets and thus can be used for the treatment of diseases which are due to thromboembolic occurrences such as strokes, arterial occlusion diseases or myocardial infarction as well as inflammations, diseases of tumors or osteoporosis.

DESCRIPTION OF THE INVENTION The present invention relates to compounds of the general formula I, where X, Y and Q independently denote a hydrogen or CH W denotes a hydrogen or NR ° R00 Z denotes a hydrogen, CH or C-OH A, E and G independently denote a valence break or an alkylene chain - (CH2) n B denotes a valence break and also denotes a carbonyl group in the case that Z equals ND denotes a side chain in the form of - (CHR3) m -COO- or = CR3-C00-n denotes 1 -5 m denotes 0, 1 R1, R2 independently denotes a hydrogen, lower alkyl or aryl or together they form a 5-membered or 6-membered carboxylic ring, R3 denotes a hydrogen or a group -OR5 or -NR6R7 R4 denotes a hydrogen or a group -OR5 R5 denotes a hydrogen, lower alkyl, aryl or arylalkyl RD denotes a hydrogen, lower alkyl or arylalkyl R7 denotes a hydrogen, lower alkyl, arylalkyl, acyl, alkylsulfonyl or arylsulfonyl R °, R00 independently denotes a hydrogen, lower alkyl, aryl, arylalkyl, hetaryl, acyl or a heterocyclic or carboxylic ring optionally substituted or, together with hydrogen at which they are linked, they form a ring of 5 members or 6 members optionally substituted which can contain in addition more than 1 to 3 heteroatoms or they denote a group Rooo I -C-MH R000 denotes a hydrogen, lower alkyl, arylalkyl or a group NHR0000 R0000 denotes a hydrogen, lower alkyl, arylalkyl, acyl, alkylsulfonyl or arylsulfonyl as well as pharmaceutically acceptable salts thereof.

The lower alkyl may in any case represent a branched chain or a C 1 -C 6 alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl or hexyl in particular methyl, ethyl, propyl, isobutyl and pentyl.

Aryl usually denotes a residual phenyl which is optionally substituted once or at different times.

The arylalkyl usually denotes an unsubstituted or one-time or substituted-in-cross other than benzyl, phenethyl, phenylpropyl, phenylbutyl or phenylpentyl, preferably a benzyl, phenethyl or phenylpentyl residue. Residues C1-C6 alkyl and preferably methyl, ethyl or isopropyl as well as chloro, bromo, fluoro or hydroxy, methoxy, benzyloxy, acetyloxy, carboxy, ethoxy-carbonyl, aminocarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, cyano, amino, methylamino, dimethylamino, benzylamino, acetylamino, benzoylamino and an amidino group occurred in consideration as substituents.

Acyl usually denotes a formyl, acetyl, propionyl, butyryl or benzoyl residue, in particular in acetyl or benzoyl residue.

Alkylsulfonyl usually denotes a methanesulfonyl, ethanesulfonyl, propanesulfonyl or a butanesulfonyl residue, in particular a butanesulfonyl residue. Arylsulfonyl usually denotes a benzene sulfonic acid or the residue of toluenesulfonyl acid.

If the residues R1 and R2 together form a 5-membered or 6-membered carboxylic ring, this is then a saturated or unsaturated 5-6 membered ring which is optionally substituted once or several times in a lower alkyl such as a ring cyclopentyl, cyclohexyl, cyclopentenyl or cyclohexenyl.

The compounds of the general formula I contain at least one asymmetric carbon atom and in addition the optionally active compounds of the general formula I is also a subject subject of the present invention. In addition, the present invention relates to conformational isomers of the compounds of the general formula I which may occur.

Preferred compounds are the compounds of the formula I in which the group AB represents a group (CH?) L-3 or (CH?) L-3 -CO and Q, W, X, Y, Z, D, R1 , R2 and R4 have the state meanings.

The compounds of the formula I are particularly preferred in which the group A-B denote a methylene, ethylene, carbonyl or methylenecarbonyl group and Q, W, X, Y or Z denotes a hydrogen. The compounds of the general formula I are preferred according to the well-known methods by ester hydrolysis of the general formula II (II) in which R1, R2, R3, R4, A, B, E, G, Q, Wf X, Y, Z and m have the meanings given above and R8 denotes a methyl, ethyl, tert-butyl, phenyl or benzyl.

The compounds of the general formula II are preferred according to the reaction path shown in scheme 1.

SCHEME 1 I) "Carbonyl- Synthon" SCHEME 1 R1, R2, R4, R8, A, B, D, E, G, Q, W, X, Y, and Z have the meanings mentioned above in scheme 1. "carbonyl synthon" usually denotes phosgene, diphosgene, triphosgene, carbonyldiimidazole, dimethyldiethyl carbonate or diphenyl carbonate, methyl chloroformate or ethyl chloroformate in particular carbonyldiimidazole, diethyl carbonate or ethyl chloroformate. MN3 denotes a metal azide such as lithium, sodium, potassium, tributyltin or magnesium azide, in particular lithium azide or sodium azide. TMSN3 is the watering for trimethylsilyl azide.

The compounds of the general formula IV that can be prepared according to the reaction path shown in scheme 2.

ESQUENA 2 c) hydrolysis of the phthalimide; d) hydrogenation of the benzyl group; e) reduction of the nitrous group; g) AcOH / 100 ° C / 3 h; h) HCL / THF / H20.

SCHEME 2 E, G, Q, X and W have the meanings mentioned above in scheme 2; L usually denotes a leaving group such as chlorine, bromine, iodine, mesylate, triflate or tosylate in particular chlorine or tosylate.

The compounds of the general formula V can be prepared in reaction pathways as shown in scheme 3.

SCHEME 3 a) Wittig reaction; b) Pd / C / H2; c) unfolding of ketals; d) Wittig reaction; e) epoxidation; f) orgametalica reaction.

SCHEME 3 In scheme 3 R1, R2, R3, A, B, and L have the meanings mentioned above and in the case that B denotes a carbonyl group L can also denote a hydroxyl group; p denotes the number 1 or 2.

The same compounds of the general formula VI are commercially available and can in special cases be obtained by oxidation in alcohol of the general formula XX wherein D, R4 and R8 have the meanings mentioned above.

The compounds of the general formula VII can be prepared by reacting a compound of the general formula VI with an organometallic compound of the general formula XXI wherein R1, R2, A and B have the aforementioned meanings of a metal such as lithium, magnesium or titanium.

The compounds of the general formula VIII are prepared according to known processes by reacting a compound of the formula VI with a phosphorylid of the general formula XXII in which R, A, B and p have the meanings mentioned above, R9 denotes a butyl, phenyl or p-tolyl and Hal "denotes chlorine, bromine or iodine.

The compounds of the general formula XI are commercially available and can be prepared in special cases by epoxidation in an olefin of general formula XXIII (XXIII) wherein R1, R2, A, B, and L have the meanings mentioned above. The compounds of the general formula XII are usually commercially available from 2-piperidinocarboxylic acid derivatives; in special cases the compounds of formula XII can be prepared by reaction in a commercially available 3- or 4-piperidone of formula XXIV with a commercially available acetic acid ester of the general formula XXV R «OOC-CH2 3 (XV) wherein R3 and R8 have the meanings mentioned above or with a Wittig reagent of the general formula XXVI wherein R3, R ° R9, and Hal "having the meanings mentioned above, The same compounds of the general formula XX are commercially available and can in special cases be obtained according to known processes by hydrogenation of the nucleus of a carboxylic acid of aryl of the general formula XXVII (XXVII) in which R4, R8 and D having the meanings mentioned above.

The compounds of the general formula XXI are each commercially available or can be synthesized in situ according to the general processes for the production of the organometallic compounds.

The compounds of the general formula X can be obtained according to known processes by reacting a compound IX with a Wittig reagent of the general formula XXVIII Bal '"1 * ~ > '-' -RB9 (XXVIII) in which R1, R9 and Hal having the meanings mentioned above.

The same Wittig reagents of formula XXII or formula XXVI or of formula XXVIII are commercially available and can be prepared from the corresponding commercially available halogen compounds and triphosphines.

The hydrolysis of an ester of the general formula II to form the corresponding carboxylic acid of the general formula I is carried out according to the usual methods by treatment of a carboxylic acid ester of the general formula II in water or in a water mixture, tetrahydrofuran, dioxane, methanol or ethanol preferably in a mixture of tetrahydrofuran in water with a hydroxide such as sodium hydroxide, potassium, lithium preferably sodium or lithium hydroxide or with an acid such as hydrochloric acid, sulfuric acid or trifluoroacetic acid preferably the trifluoroacetic acid and at temperatures between room temperature and 80 ° C preferably at room temperature. The reaction of a compound of general formula XIII with 1-benzylpiperazine or 4-hydroxy or 4-oxopiperidine (scheme 2) or the reaction of a compound of formula XI with a compound of formula XII or a compound of formula XI with an amine of formula XII is usually carried out in an aprotic solvent such as toluene, tetrahydrofuran, diethyl ether, dimethylformamide chloride or methylene, preferably dimethylformamide or tetrahydrofuran, using a base such as potassium hydride, sodium hydride, potassium carbonate or sodium bicarbonate. , preferably sodium hydride or sodium carbonate, and at temperatures between room temperature and 180 ° C, preferably at 120 ° C or at room temperature.

The reaction between 3- or 4-piperidone of formula XXIV and an ester of formula XXV is carried out under the conditions of an allyl reaction in a solvent such as methanol, ethanol, toluene, tetrahydrofuran, diethyl ether or dimethylformamide, preferably tetrahydrofuran or dimethylformamide, using a base such as sodium or potassium methylate or ethylate, sodium hydride, potassium hydride, lithium diisopropylamide, potassium hexamethyldisilazide, preferably sodium hydride or lithium diisopropylamide, and at temperatures between -78 ° C and 90 ° C, however, preferably between -78 ° C and room temperature. The benzyl protecting groups are removed if necessary by catholytic hydrogenation such as e.g. with hydrogen in carbon and palladium.The Mitsunobu reaction between a compound of formula XVIII and phthalimide is carried out according to processes known from the literature (Mitsunobu O., Synthesis, page 1 (1981)).

A ketone of formula XVI is amidatedly reduced with dibenzylamino or an amine of formula XXX according to processes known from the literature by reaction of the ketone and amine component in a solvent such as methanol or ethanol in the presence of a reductive agent such as sodium cyanoborohydride. or sodium triacetate borohydride in addition to a Lewis or Bronsted acid such as hydrochloric acid, acetic acid, titanium tetrachloride or titanium tetraisopropylate and at a temperature between 0 ° C and 100 ° C preferably at room temperature or in the presence of a catalytic hydrogenation such as platinum dioxide and a hydrogen atmosphere (Borch RF, Org Synth Coil Vol 6, 499 (1988) Heinzelman RVZ Chem 8, 270 (1968), Mattson RF, J. Org. Chem. 55, 2552 (1990), Barney CL Tetr. Letters 31, 5547 (1990), Huntchins RO, J. Org. Chem. 46, 3571 (1981)).

The nitrosation of a compound of general formula XIV to form a compound of formula XV which is usually carried out with sodium nitrite or isoamy nitrile in water or ethanol in addition to an acid such as hydrochloric acid or acetic acid and at a temperature between -20 ° C and 80 ° C preferably at room temperature.

The reduction of a nitroso compound of general formula XV is carried out according to known processes by reaction of a compound of formula XV in a solvent such as water, acetic acid, ethanol, tetrahydrofuran or diethyl ether, preferably acetic acid or tetrahydrofuran, with a reductive agent such as elemental zinc, lithium aluminum hydride or sodium aluminum hydride, preferably elemental zinc or hydrophobic lithium aluminum, and at temperature between room temperature and 120 ° C, however, preferably at 70 ° C. The conversion of a compound of general formula XV into a compound of formula IV which can also be carried out by hydrogenolysis using a catalyst such as α-aladium carbon (Hatt, HH, Org Synth, Coil, Vol.2, 211 (1943) Schüler FW, J. Amer. Chem. Soc. 73, 4996 (1951)). An alcohol of the general formula XX is oxidized to a ketone of the general formula VI according to known methods such as Jones oxidation (Jones ERH, J. Chem. Soc. 36 (1946)), Swern oxidation (Swern D. , Tetrahedron 34, 1651 (1978)), Dess-Martin oxidation (Dess DB, Martin JC, J. Org. Chem. 48, 4155 (1983)) or using a urotropin complex in bromine as an oxidation agent (Yavari I ., J. Chem. Res. (P) 274 (1994)). If necessary, the Wittig reagents used are prepared analogously for processes known from the literature (Buddras J., Angew. Chem. 80, 535 (1968): Bestmann H.J. Angew. Chem. 77, 620, 651 (1965); Wittig G.

See. Deutsch. Chem. Ges. 88, 1654 (1955)).

The Wittig reaction is carried out according to known methods such as heating reactants for reflux in an aprotic solvent such as benzene, toluene or xylene, preferably toluene.

The hydrolysis of phthalimide is usually carried out according to known methods by treating phthalimide with hydrazine hydride or semi-concentrated mineral acid such as hydrochloric acid or sulfuric acid, preferably with hydrazine hydrate or hydrochloric acid, at room temperature.

The amines are usually acylated in a solvent such as methylene chloride, dimethylformamide or pyridine, preferably methylene chloride or pyridine, in addition to an auxiliary base such as triethylamine or 4-dimethylaminopyridine and at temperatures between -10 ° C and 50 ° C, however, preferably at room temperature.

A ketal of the general formula VIII is split according to standard methods of organic chemistry (* ORGANIKUM; veb Deutscher Verlag der Wissenschaften, Berlin 1977, page 486, 490). Olefinic double bonds are similarly catalytically hydrogenated for known processes of the literature. Nose, Chem. Pharm. Bull. 38, 2097 (1990); Tamura M. Bull. Chem. Soc. Jpn. 53 561 (1980); Liu H. J., Synth. Commun. 15, 965 (1985); Chido N., J. Chem. Soc. Chem. Commun. 994 (1990); Büchi G., J. Amer. Chem. Soc. 89, 6745 (1967); Erns I., Coil. Czech Chem. Comm. 24, 3341 (1959); Johnson W.S., J. Amer. Chem. Soc. 79, 1995 (1957); Muchowski J.M., Can J. Chem. 47, 857 (1969)).

An olefin of formula VII of formula X or formula XXVIII is epoxidized according to processes known from the literature by reaction with peroxy acid such as m-chloroperbenzoic acid, peracetic acid or trifluoro peracetic acid, preferably m-chloroperbenzoic acid , in an aprotic solvent such as methylene chloride and at temperatures between -30 ° C and 50 ° C, preferably at room temperature; in addition to the aforementioned olefins which can be converted into the corresponding epoxides by means of Sharpless epoxidation (Sharpless K.B., Org Syntheses, Vol. 63, 66 (1985)).

The organometallic reaction mentioned in scheme 3 which is usually a Grignard reaction which is carried out by processes known from the literature. However, if necessary, the magnesium reagent of formula XXI which can be transferred into a reactive titanium or lithium reacted with a carbonyl compound of formula VI (Reetz M.T., Chem. Ver. 118, 1421 (1985)).

An aminoalcohol of formula III is converted into an oxazolidinone of formula II according to processes known from the literature by reaction of an aminoalcohol of formula III with diethyl carbonate (Evans DA, Org Syntheses, vol 68, 77 (1989)) or carbonyldiimidazole (Chadwick DI, J. Chem. Soc. Perkin Trans. 481 (1984); Gefken D. Arch. Pharm.313, 817 (1980)) or phosgene (Newman WS, J. Am. Chem. Soc. 73, 4199 (1951)) or diphosgene or triphosgene (Hassner A., Synth Commun.23, 2839 (1993)), or a methyl, ethyl or benzyl ester of chloroformic acid (Kanoshinzo, J. Org. Chem. 53, 3865 (1988)) in a solvent such as methylene chloride, dimethylformamide, toluene, dioxane, tetrahydrofuran, water or diethyl ether, preferably dimethylformamide, methylene chloride or tetrahydrofuran, and at a temperature between -50 ° C and 80 ° C, preferably at room temperature.

Catalytic hydrogenation of a compound of formula XXVII is carried out in a solvent such as methanol or ethanol in addition to a catalyst such as ruthenium oxide, rhodium oxide or strontium carbonate in palladium, preferably rhodium oxide, in a hydrogen atmosphere at a pressure of 1-200 bar, preferably at 200 bar, and at a room temperature and 200 ° C (Rastin RH, I. Chem. Soc. 1855 (1949) The opening of an epoxide of formula V with an amine of formula IV usually takes place in a solvent such as methanol, ethanol, dimethylformamide or toluene, preferably ethanol or toluene, and at a temperature between 0 ° C and 120 ° C, preferably 80 ° C.

The opening of an epoxide of formula V with a metal azide is carried out according to the methods known from the literature by reacting an epoxide of formula V with a metal azide such as lithium, sodium, potassium, tributyltin or magnesium azide, preferably sodium azide, in a solvent such as methanol, ethanol, 1,4-dioxane, water, dimethylformamide, tetrahydrofuran, acetonitrile or hexamethylphosphorotriamide or in a mixture of said solvents, but preferably in methanol, mixtures of dimethyl formamide or 1, 4 -diaoxano-water, and at a reaction temperature between -10 ° C and 120 ° C, preferably 80 ° C (ventaverf CA, J. Am. Chem. Soc. 76, 1231 (1954); Satio S. Tetrahedron Lett. , 4153 (1989), Hudlicky T., J. Chem. Soc. Perkin Trans. I, 2907 (1991)). An epoxide of formula V is usually reacted with trimethylsilylazido in a solvent such as methanol, tetrahydrofuran, methylene chloride, chloroform, dichloroethane or benzene, preferably tetrahydrofuran or methylene chloride, without further additives or using additives such as titanium tetraisopropylate, triisopropylate aluminum, dichlorotitanium diisopropylate or diethylaluminum fluoride, preferably titanium tetraisopropylate or aluminum triisopropylate and at a temperature between 0 ° C and 100 ° C, but preferably at room temperature (Emziane M., Synthesis, p.541 (1988); S., Tetrahedron Lett 26, 5309 (1985), Blandy C, Tetrahedron Lett 24, 4189 (1983), Jung ME, J. Org Chem 56, 2614 (1991)).

An azido of formula XXIX is converted to an amine of formula XXX according to known methods: Suami T., Bull. Chem. Soc. Jpn., 51, 855 (1978); Boullanger P., Bull. Soc. Chim. Fr., p. 2149 (1973); Ackerman K., Can. J. Chem., 50, 3886 (1972); Hanessian S., Chem. Ind., P. 1296 (1965); Horner L., Liegigs Ann. Chem., 591, 117 (1955); Koziara A. Synthesis, p. 487 (1987); Vogel E., Ang. Chem. Int. De. Engl., 18, 962 (1979); Purwono B., Synlett, 3, 231 (1992).

The compounds of formula I contain one or more chiral centers and can thus be present in an optical or racemic active form. The racemates can be separated mechanically or chemically in their enantiomers by well known methods. The diastereoisomers are preferably formed from a racemic mixture by reaction with an optical active acid such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyl tartaric acid, mandelic acid, malic acid, lactic acid or various sulfonic acid optically active camfor such as ß-camphor sulfonic acid. This is possibly also treated to obtain optically active compounds of formula I by the methods mentioned above to use starting materials (e.g., those of formula II) which are already optically active.

The alkali salts, ammonium salts, trifluoroacetates or hydrochlorides are all previously used as pharmaceutically acceptable salts which are usually produced, for example, by titration of the compounds with organic or inorganic acids or bases such as potassium sodium bicarbonate, hydroxide solution sodium, potassium hydroxide solution, amines or aqueous ammonia such as trimethylamine or triethylamine, trifluoroacetic acid or hydrochloric acid. The salts are usually purified by precipitation of acetone in water.

The novel substances of formula I and the salts thereof according to the invention can be administered entirely or parenterally in the form of a liquid or solid. In all these connections the usual forms of administration occur in consideration such as tablets, capsules, coating tablets, syrups, solutions, suspensions etc. The water is preferably used as the injection medium containing the usual additives in injectable solutions such as stabilizing agents, solubilizers and buffers.

Such additives are for example tartrate and citrate buffers, ethanol, complexing agents (such as diaminotetraacetic acid in ethylene and non-toxic salts thereof), high molecular polymers (such as polyethylene oxide liquid) in order to regulate the viscosity. The carrier liquids for injectable solutions have to be sterile and are preferably distributed in ampoules. The carrier solids are e.g. starch, lactose, mannitol, methylcellulose, talc, highly distributed silicic acids, high molecular fatty acids (such as stearic acid), gelatins, agar-agar, calcium phosphate, magnesium stearate, vegetable and animal lard, high molecular polymers in solids (such as polyethylene glycols); preparations that are suitable for oral application which may optionally contain dulsifiers and seasonings.

The dose may depend on several factors such as the manner of administration, species, age or / and individual health states. The doses may be administered daily for about 10-1000 mg / human, preferably 100-500 mg / human and the doses distributed may be taken once or several times.

Within the meanings of the present invention the following pyridazine and pyridine derivatives are preferred in addition to the compounds mentioned in the examples and the compounds derived by combination of all the meanings of substituents mentioned in the claims: 1) l- acid. { 2- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -ethyl} - piperidine-4-carboxylic 2) l- acid. { 3- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -propyl} -piperidine-4-carboxylic 3) l- acid. { 4- [2-oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyl} -piperidine-4-carboxylic 4) l- acid. { 5- [2-Oxo-3- (3, 4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -pentyl} -piperidine- 4-carboxylic ) 1- [2-oxo-5-phenyl-3- (3,, 5, 5-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidine- 4-carboxylic acid 6) 1- [2-OXO-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidine- 4 -carboxylic 7) l- acid. { 2- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -acetyl} -piperidine-4-carboxylic 8) l- acid. { 5- [2-Oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bi? Iridinyl-4-yl) -oxazole idin-5-yl] -pentanoyl} -piperidine-4-carboxylic 9) 1- (2-Oxo-3- (4-pyridin-4-yl-piperazin-1-yl) -oxazolidin-5-ylmethyl) -piperidine-4-carboxylic acid ) acid. { l- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-3-yl} - acetic 11) (l-. {2- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] acid] -ethyl.}. -piperidin-3-yl) -acetic. 12) acid. { 1- [2-OXO-3- (3,4,5,6-tetrahydro-2 H- [1,4'] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-3-yl} - acetic 13) acid (L- { 4- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5- il] -butyryl.}. -piperidin-3-yl) -acetic 14) (3-hydroxy-l-. {5- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin- 5-yl] -pentanoyl.}. -piperidin-3-yl) -acetic ) (3-hydroxy-l-. {2- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin- 5-yl] -acetyl.}. -piperidin-3-yl) -acetic 16) acid. { 3-hydroxy-l- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-3- il} - acetic 17) acid. { 3-hydroxy-l- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-3- il) -acetic 18) acid (3-hydroxy-l-. {4- [2-OXO-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) ) -oxazolidin-5-yl] -butyl.} - piperidin-3-yl) -acetic acid 19) acid. { l- [2-Oxo-4-phenyl-3- (3,4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4- il} - acetic ) acid. { 4-hydroxy-l- [2-oxo-5-phenyl-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] - piperidin-4-il} - acetic 21) acid. { l- [4-Methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin- 4- il} - acetic 22) acid. { l- [4-Methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-3- il} - acetic acid 23) { 3-hydroxy-l- [5-methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] - piperidin-3-il} - acetic 24) 1- [2-oxo-5-phenyl-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin acid -4- carboxylic ) (l-. {2- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] acid] -ethyl] -piperidin-4-yl) -acetic 26) (l- { 4- [2-oxo-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyl.}. -piperidin-4-yl) -acetic 27) (4-hydroxy-l-. {2- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin- 5-yl] -ethyl.}. -piperidin-4-yl) -acetic 28) acid (4-hydroxy-l-. {5- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin- 5-yl] -pentyl.}. -piperidin-4-yl) -acetic acid 29) (l-. {2- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [ 1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -acetyl.} - -piperidin-4-yl) -acetic acid ) acid (L-. {5- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] ipyridinyl-4-yl) -oxazolidin-5-yl] -pentanoyl.}. -piperidin-4-yl) -acetic 31) acid (4-hydroxy <il-. {2- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin -5-yl] -acetyl.}. -piperidin-4-yl) -acetic 32) acid (4-hydroxy-l-. {4- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin- 5-yl] -butyryl.}. -piperidin-4-yl) -acetic 33) acid. { l- [2-Oxo-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-4-yl) -acetic 34) acid. { 4-hydroxy-l- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-4- il) - acetic ) l- acid. { 2- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -ethyl} -piperidin-3-carboxylic 36) l- acid. { 4- [2-oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyl} -piperidine-3-carboxylic acid 37) l- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidine-3-carboxylic acid 38) l- acid. { 4- [2-oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyryl} -piperidine-3-carboxylic acid 39) 1- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidine-2-carboxylic acid 40) l- acid. { 5- [2-Oxo-3- (3,4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -pentyl} -piperidine-2-carboxylic acid 41) l- acid. { 4- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyryl} -piperidine-2-carboxylic acid 42) '1 - [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1, 4'] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-2-acid carboxylic 43) l- acid. { 2- [5-Methyl-2-oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -ethyl} -piperidine- 2-carboxylic 44) l- acid. { 5- [4-Methyl-2-oxo-3- (3, 4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -pentyl} -piperidine-2-carboxylic acid 45) l- acid. { 4- [5-methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyryl} -piperidine-2-carboxylic acid 46) l- acid. { 5- [4-Methyl-2-oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -pentanoyl} -piperidine-2-carboxylic acid 47) 1- [2-oxo-3- (4-pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid 48) 1- [2-oxo-3- (l-pyridazin-4-yl-piperazin-4-yl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid 49) 1- [2-oxo-3- (l-pyridazin-4-yl-piperazin-4-yl) -oxazolidin-5-carbonyl] -piperidine-4-carboxylic acid 50) 1- [2-oxo-3- (4-pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-carbonyl] -piperidine-4-carboxylic acid 51) 1- [2-oxo-3- (4-pyridazin-4-yl-piperazin-l-ii; oxazolidin-5-carbonyl] -piperidine-4-carboxylic acid 52) acid. { 1- [2-Oxo-3- (l-pyridazin-4-yl-piperazin-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4-yl} -acetic 53) acid. { 4-hydroxy-l- [2-oxo-3- (4-pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-yl] -piperidin-4-yl} -acetic 54) l- acid. { 3- [2-oxo-3- (4-pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-yl] -propyl} -piperidine-4-carboxylic 55) l- acid. { 3- [4-Methyl-2-oxo-3- (4-pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-yl] -propionyl} -piperidine-4-carboxylic 56) 1- [4-Methyl-2-oxo-3- (4-pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid 57) acid (butan-1-sulfonylamino) -. { 1- [4-methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4- il} - acetic 58) (butan-1-sulfonylamino) - (l-. {3- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4]] bipyridinyl-4 -yl) -oxazolidin-5-yl] -propyl.}. -piperidin-4-yl.} - acetic acid 59) acid (butan-1-sulfonylamino) -. { 1- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidin-4-yl} - acetic 60) 4- [2-oxo-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -cyclohexanecarboxylic acid 61) 4- [2-oxo-3- (3, 4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -cyclohexanecarboxylic acid 62) 4- acid. { 3- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -propyl} -cyclohexanecarboxylic 63) 3- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -cyclohexanecarboxylic acid 64) 4 acid -hydroxy-4-. { 3- [2-oxo-3- (3, 4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -propyl} -cyclohexanecarboxylic 65) acid. { 4- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -cyclohexyl} -acetic 66) [4-hydroxy-4- acid. { 3- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -propyl} -cyclohexyl} - acetic 67) acid. { 1,4-Dihydroxy-4- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -cyclohexyl} - acetic 68) 3- acid. { 2- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -ethyl} -cyclohexanecarboxylic acid 69) 2-. { 4- [2-OXO-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-yl] -butyl ester} -cyclohexanecarboxylic 70) 4- [4-methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin-5-ylmethi acid} -cyclohexanecarboxylic 71) 4- [2-oxo-3- (l-pyridazin-4-yl-piperidin-4-yl) -oxazolidin-5-ylmethyl] -cyclohexanecarboxylic acid 72) 4- [2-oxo-3- (4-pyridazin-4-yl-piperidin-l-yl) -oxazolidin-5-ylmethyl] -cyclohexanecarboxylic acid 73) acid (butan-1-sulfonylamino) -. { 4- [4,5-dimethyl-2-oxo-3- (4- (pyridazin-4-yl-piperazin-1-yl) -oxazolidin-5-ylmethyl] -1-hydroxy-cyclohexyl} -acetic acid 74) l- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl-4- (3,4,5-trimethoxyphenyl) -oxazolidin -5-carbonyl] -piperidine-4-carboxylic, MP 108-114 ° C 75) 1- [4- (3,4-dimethoxy-phenyl) -2-OXO-3- (3, 4, 5, 6) acid -tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] -piperidine-4-carboxylic acid. P.f. 118 ° C 76) 1- [4- (4-cyano-phenyl) -2-OXO-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin- acid 5-carbonyl] -piperidine-4-carboxylic acid. P.f. 100-105 ° C 77) 1- [4-Methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5 acid -carbonyl] -piperidine-4-carboxylic acid. P.f. 73-75 ° C 78) (5S) -l- [5-methyl-2-oxo-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5 acid ilmethyl] -piperidine-4-carboxylic acid. P.f. 223 ° C (decomp.) 79) 1- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] ipyridinyl-4-yl) -4- (3-trifluoromethylphenyl) -oxazolidin-5 acid ilmethyl] -piperidine-4-carboxylic pf 125-130 ° C 80) l- [4- (4-chlorophenyl) -2-oxo-3- (3,4,5,6-te rahydro-2H- [1,4 '] bipyridinyl-4-yl acid -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid pf 110-115 ° C 81) 1- [4- (4-isopropylphenyl) -2-oxo-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5 acid ilmethyl] -piperidine-4-carboxylic acid 82) l- [4- (4-tert-Butyl-phenyl) -2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) - oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid 83) l- acid. { 3- [1- (2-Amino-pyrimidin-4-yl) -piperidin-4-yl] -2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic 84) l- acid. { 2-oxo-3- [1- (2-piperidin-1-yl-pyrimidin-4-yl) -piperidin-4-y1] -oxazolidin-5-ylmethi} -piperidine-4-carboxylic 85) 1- acid. { 2-Oxo-3- [1- (2-phenylamino-pyrimidin-4-yl) -piperidin-4-yl] -oxazolidin-5-ylmethyl} -piperidine-4-carboxylic acid 86) l-. { 2-oxo-3-. { l- [2- (Pyrimidin-2-ylamino) pyrimidin-4-yl] -piperidin-4-y1} -oxazolidin-5-ylmethyl) -piperidine-4-carboxylic acid 87) l- acid. { 3- [2-amino-pyrimidin-4-yl) -piperidin-4-yl] 2-oxo-hexahydro-benzooxazol-7a-ylmethyl} -piperidine-4-carboxylic 88) l- acid. { 3- [1- (2-Benzylamino-pyrimidin-4-yl) piperidin-4-yl] -2-oxo-hexahydrocyclopentaoxazol-6a-ylmethyl} -piperidine-4-carboxylic 89) l- acid. { 3- [1- (2-guanidino-pyrimidin-4-yl) piperidin-4-yl] -2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic 90) l- acid. { 3- [1- (2-Acetimidoylamino-pyrimidin-4-yl) piperidin-4-yl] -2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic acid 91) l-. { 3- [1- (2-Amino-pyrimidin-4-yl) -piperidin-4-yl] -4-ethyl-2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic 92) 1- [4-ethyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidine acid -4-carboxylic 93) l- [4-Butyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin - 4- carboxylic 94) l- [2-oxo-4-phenyl-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin -4-carboxylic 95) l- [4-hexyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidine acid -4- carboxylic 96) 1- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -4- (2-p-tolyl-ethyl) - acid oxazolidin-5-ylmethyl] -pipéridin-4-carboxylic acid 97) l- acid. { 3- [1- (2-Benzylamino-pyrimidin-4-yl) -piperidin-4-yl] -4-butyl-2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic The following examples show some variant processes, which can be used to synthesize the compounds according to the invention. However, they are not constant to limit the subject matter of the invention. The structure of the compounds is checked by means of XH and optionally by 13C-NMR spectroscopy as well as by mass spectrometry. The purity of the substances is determined by means of C, H, N and by thin layer chromatography.

EXAMPLE 1 1- [(5S) -2-OXO-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4 acid -carboxylic a) A solution of 46 g (0.4 mol) 4-chloropyridine and 123.5 g (0.86 mol) ethylene ketal of 4-piperidone is heated for 48 hours at reflux in 400 ml of p-xylene.

Subsequently the reaction mixture is cooled, the precipitate is precipitated, the filtrate is removed by evaporation, the mother liquor is concentrated to dryness and the residue is purified by silica gel column chromatography (alkaline methanol in saturated ammonium in ethyl acetate 9 / 1). In this way 79.7 g (90%) 8-pyridin-4-yl-1,4-dioxa-8-aza-spiro [4.5] decane is obtained as a white powder. M / e = 220; p.f. = 65 ° C. b) a solution of 79.7 g of the ketal is prepared in a) in 2 1 of tetrahydrofuran is mixed in hydrochloric acid 116 n and the reaction mixture is stirred for 2 hours at room temperature. Subsequently the tetrahydrofuran is removed in a vacuum in a rotary evaporator, the hydrochloric acid is formed in alkaline with a solution of semi-concentrated ammonium hydroxide and extracted in 4 times with 100 ml of methylene chloride each time. After the combined organic extracts are dried over sodium sulfate and the solvent is removed, the residue is purified by means of column chromatography on silica gel. 64.2 g (100% yield) 2, 3, 5, 6-tetrahydro- [1,4 '] bipyridinyl-4-one is thus obtained as a gray powder. M / e = 176; p.f. = 102 ° C. c) A solution of 32 g of ketone produced in b) and 19.9 ml of benzylamine in 400 ml of methylene chloride is mixed in portions with 50.4 g of sodium borohydride triacetate, while cooling on ice. Subsequently, 12 ml of 100% acetic acid is added dropwise, the reaction mixture is then allowed to stir for 4 hours at room temperature and then mixed with 100 ml of water. After the phases are separated, the aqueous phase is formed alkaline at pH 12 with a 2 n sodium hydroxide solution and extracted in 5 times with 50 ml of methylene chloride each time. The combined organic extracts are then dried over sodium sulfate and the solvent is removed on a rotary evaporator, benzyl- (3, 4,5,6-tetrahydro-2H- [1,4 '] -bipyridinyl-4-yl) -amino is obtained in this way, it is taken in 100 ml of methanol and the solution is mixed with 3.5 g of carbon in 10% palladium. The methanol mixture is then hydrogenated at room temperature until the hydrogen cannon is supplemented (30 hours), the catalyst is then removed by filtration and the mixture is concentrated on a rotary evaporator. 22 g 3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-ylamino is obtained in this way as a slightly yellow viscous oil which crystallizes slowly. M / e = 177, 1 H-NMR (d 6 -DMSO); d = 8.10 ppm (d, 2H); 6.85 ppm (d, 2H); 3.80 ppm (d with fine resolution, 2H); 2.85 ppm (t with fine resolution, 2H); 2.70 ppm (m, ÍH); 1.70 ppm (d with fine resolution, 2H); 1.20 p? M (q with fine resolution, 2H); p.f. = 68 ° C. d) A mixture of 5.7 g (2R) -glycidyl tosylate (Fluka I GmbH), 4 ml of the piperidine-4-carboxylic ethyl ester and 3.5 g of potassium carbonate in 100 ml of acetonitrile is heated for 2 hours under reflux . After cooling the reaction mixture is mixed with 50 ml of water and extracted 3 times each with 50 ml of methylene chloride and 50 ml of diethyl ether. After the combined organic phases are dried over sodium sulfate and the solvent is removed in a rotary evaporator, the residue is purified by means of column chromatography on silica gel (methanol-saturated ammonium in ethyl acetate 95/5). In this way, 2.5 g of (2S) -l-oxiran-2-ylmethyl-piperidine-4-carboxylic acid ethyl ester are obtained.

^ -NMR ^ -DMSO); d = 4.05 ppm (q 2H) í? -T > 0 fm, 1H; -2 .-. "55 (double-t, 1H); 2.85 (double-t, ÍH); 2.70 (q, TR), 2.65 (dd, ÍH); 2.45 (dd, ÍH); 2.30 (m, ÍH); 2.15 (dd, 1H), - 2.02 (m, 2H); 1.75 (broad d, 2H); 1.52 f sextet, 2? 1-5 < tf 3H). e) A solution of 0.43 g of the amine produced in sf and 0.173 g of the oxirane produced -in d) -in 10 minutes of ethanol is heated for 48 hours under reflux. Subsequently - the ethanol is removed in a vacuum and the residue is purified by column chromatography on silica gel (methanol-saturated ammonium in ethyl acetate € 5/15). The product obtained (325 mg) from this pathway is 2 ml of dimethylformamide, the solution is washed with 2X > 0 ratj of carbonyldiimidazole and the reaction mixture is stirred for 15 hours at room temperature, Subsequently the reaction mixture is mixed with 10 ml of water and this is moved in 3 times with 10 ml of cathylene chloride cacta time. After the combined organic phases are dried over sodium sulfate and the solvent is removed in a vacuum, the residue is purified by means of HPLC preparations (RP 18, methanol buffer (pH = 7.5.) 7/3). This path yields 235 mg of ethyl ester of (1- (5S; -2-C O-3-Í3,4,5,6-tetrahydro-2H- [1,4'] ipiridinyl-4-yl) - oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid.

M / e = 416; XH-NMR (d6-DMSO); d = 8.12 ppm (d, 2H); 6.82 (d, 2H); 4.60 (q, 1H); 4.05 (q, 2H); 3. (broad d, 2H); 3.75 (m, ÍH); 350 (t, ÍH); 3.15 (t, ÍH); 2.90 (double-t, 2H); 2.75 (, 2H); 2.50 (m, 2H); 2.25 (m, 1H); 2.10 (m, 2H); 1.80-1. 0 (, 9H); 1.12 (t, 3H).

F} A solution of 230 mg of ethyl ester prepared in e) in 2 ml tetrahydrofuran and 1 ml of water is mixed with Q. ~! ml of a 1 n sodium hydroxide solution and stirred for 1 hour at room temperature. Subsequently, the tetrahydrofuran is removed in a vacuum and the product is purified by means of an ion exchange (Dowex 50, form H). 120 mg of the title compound are obtained in this way as a white powder. FAB = 388; LH-NMR (d6-DMSO); d = 8.15 ppm (d, 2H); 6.82 (d, 2H); 4.60 (m, 1H); 4.02 (broad d, 2H); 3.75 (m, ÍH); 350 (t, 1H); 3.15 (dd, 1H); 2.95 (broad d, 2H); 2.80 (m, 2H); 2.52 (, 2H); 2.10 (m, 3H); 1.80-1.40 (m, 8H).

EXAMPLE 2 Acid l- [rac] -2-oxc-3- (3, 4,5,6-tetrahydro-2H-5 [1,4 '] ipyridinyl-4-ii) -oxazolidin-5-ylmethyl] -piperidine- 4- a fco ilico a) A mixture of 3.1 g of ethyl ester of piperidin-4-carboxylic acid, 6.4 ml of epichlorohydrin and 0.1 g of tetrabutylammonium bromide in 15 ml of toluene and 15 ml of the concentrated sodium hydroxide solution is determined by 4 hours at room temperature and subsequently mixed with 50 ml of water. The organic phase is removed, the aqueous phase is moved in 3 times with 20 ml of methylene chloride each time, the combined organic phases are dried over sodium sulfate and the solvent is removed in a vacuum. 2.1 g of the ethyl ester of (rae) -l-oxiran-2-ylmethylpiperidine-4-carboxylic acid are obtained. m / e = 213. nt) Analogically to example le), 520 mg of the ethyl ester of the acid 1- [rae] -2-oxo-3- (3, 4, 5, 6 e ra i r-: -2H- [1,4 '1 bipyridi ii-4-yl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid from 2.1 ge cxyl 2a), 2.6 g aminole) and 0.4 g carbonyldiimidazole. M / e = 416. c) Analogously to example If), 190 mg of the title compound is obtained from 520 mg of ethyl ester 2b) and 1.5 ml of the 1 n sodium hydroxide solution. FAB: 388, 1H-NMR (d6-DMS0): identical to XH-NMR compound If).

EXAMPLE 3 Acide { ! - [(rac) -2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin- 4- iii enc l-acé ico a) Analogously to example 2a), 1.6 g of 8-oxirane-2-ylmethyl-1,4-dioxa-8-aza-spiro [4.5] decane is obtained as a yellow oil from 1.43 g of the ethylene ketal of 4 -piperidone, 3.1 ml epichlorohydrin and 0.2 g bromide e te ab ilamonio. ^ -N RÍd ^ DMSO); d = 3.85 ppm (s, 4H); 3.0 (m, 1H); 2. ^ 0 (dt :, 2H); 2.60 (d, 1H); 2.50 (m, 3H); 2.40 (m, ÍH); 2.20 (dd, 1H); 1.60 (t, 4H). ^ ft b) Analogously to example le), 0.35 g 5- i1, 4-licx3- -aza-spiro [4.5] dec-8-ylmethyl) -3- (3,4,5,6, -te rahydro- 2H- [1,4 '] bipyridinyl-4-yl) oxazoiidin-2-one from 1.6 g of epoxide 3a), 1. g of amine le) and 0.4 g of carbonyldiimidazole. m / e = 402; ^ - MR (d6-DMS0); d = 8.15 pp (d, 2H); 6.82 (d, 2H); 4.60 (m, 1H); 4.0 (broad d, 2H); 3.85 (s, 4H); 3.75 (m, 1K); 3.52 (t, ÍH); 3.15 (t, ÍH); 2.90 (broad t, 2H); 2.55 (m, 6H); 1.60 (m, 8H). c) Analogously to example Ib), 1.1 g of l- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1, 'j ipyridinyl-4-yl) -xaxazidin-5-ii -methyl] -piperidin-4-one are obtained as a gray powder from 1.2 g of ketal 3b) and 10 ml of the 6 n hydrochloric acid. m / e = 358;; d = 8.20 ppm (d, 2H); 6.55. { d, 2H); 4.65 (m, ÍH); 3.95 (m, 3H); 3.50 (t, 1H); 3.20 (t, 1H); 2. 85 (m, 7H); 2.65 (dd, 1H); 2.45 (t, 4H); 1.80 (m, 2H > 1. 65 (dq, 2H). d) A mixture of 840 mg of ketone 3c) and 820 mg of epoxycarbonylethylidenetriphenylphosphorane (Aldrid GmbH &Co) in 15 ml of toluene is heated for 24 hours at 100C.

Subsequently the toluene is evaporated in a vacuum and the crude oil is purified on silica gel (ammonium Q). saturated ethanol in ethyl acetate 85/15). In this walk 920 mg of ethyl ester of acid. { 1- [(rae) -2-oxc 3- (3,, 5,6-tetrahydro-2H- [1,4'] ipyridinyl-4-yl) -xazcyidin-5-ylmethyl] -piperidin-4-ylidene } -acetic. M / e = 5 428. e) Analogously to example lf), 48 mg of the title compound is obtained as a white powder from 210 mg of 3d ethyl ester) and 0.6 ml of the 1 n sodium hydroxide solution. FAB: 400; ^ - MRÍd ^ DMSO); d = i r ß.i5 pp (d, 2H); 6.80 (d, 2H); 5.60 (s, 1H); 4.65 (m, 1H); 4.05 (broad d, 2H); 3.75 (m, 1H); 3.60 (t, ÍH); 3.20 (t, 1H); 2.QQ (m, 4H); 2.55 (m, 6H); 2.20 (m, 2H); 1.65 (m, 4H).

EXAMPLE 4 ac i ic. { l- [2-Oxo-3- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4-yl} -acetic ! _0 a A solution of 560 mg of 3d compound) in 20 ml of methane! it is mixed with 50 mg of carbon in palladium (10%) and hydrogenated at room temperature and the normal pressure to the barrel and hydrogen is complete. Then the catalyst is removed by filtration and the solution is evaporated to dryness. In this way 400 mg of the ethyl ester of the acid. { 1- [2-oxo-3- (3,, 5,6-tetrahydro-2H- [1,4 'jbi i idinyl-4-ii) -oxazoiidin-5-ylmethyl] -piperidin-4-yl} -acetic is obtained as a colorless oil, m / e = 430. b) Analogously to example lf), 180 mg of the title compound is obtained as a light gray powder from 400 mg of ethyl ester 4a) and 1.1 ml of the sodium hydroxide solution i n. FAB = 402; XH-NMR (d6-DMS0); d = s.15 ppm (d, 2H); 6.80 (d, 2H); 4.60 (m, ÍH); 4.05 (broad d, 2H) 3.75 (m, 1H); 3.50 (t, ÍH); 3.12 (t, 1H); 2.85 (m, 4H); 2.4- (m, 2H); 2.0. { m, 4H); 1.65, m, 7H); 1.12 (m, 2K).

EXAMPLE 5 acid { 4-hydroxy-l- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'3-ipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4- eleven } acét ico a) C.5 ml of diis-propylamino is mixed under nitrogen at -0 ° C with 2.3 ml of n-butyllithium (1.6 M in n-hexane). The mixture is subsequently stirred for more than 10 minutes at -10 ° C, then cooled to -78 ° C and 10 ml of dry tetrahydrofuran is added, 0.45 ml of the terpeter ester is added dropwise. acetic acid in 2 ml of dry tetrahydrofuran to the solution of lithium diisopropylamide _5 prepared in this way, the reaction mixture is then allowed to stir for 30 minutes at -7 C, this is mixed with a solution of 1.1 g of cotona 3c) in 10 ml of dry tetrahydrofuran, this is stirred for 1 hour at -78 C and subsequently heated read at room temperature. Then the reaction mixture is stirred for more than 15 hours at room temperature and then mixed with 10 ml of the saturated ammonium chloride solution. The aqueous solution is then extracted in 3 times with 10 ml of After drying, the combined organic phases were dried over sodium sulfate and the solvent was removed in a rotary evaporator, the crude product was purified by means of HPLC preparations (select B, 12μ, methanol buffer (pH 7.5). /4). 0.85 g of ester Tfl ter. bu ilo. of the acid. { 4-hydroxy-l- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] ipyridinium-4-yl) -oxazolidin-5-yl-di-yl] -piperidin -4-i} -3acetic It is obtained as a yellow areite. M / e = 474. b) A solution of 100 mg of ester ter. butyl 5a) in 2 ml of trifluoroacetic acid is stirred for 5 hours at room temperature. Subsequently, the reaction mixture is evaporated to dryness, the residue is taken up in 3 ml in water and the product is purified by means of an ion exchange (Do ex 50, form H). 30 mg of the title compound is thus obtained as a white powder. 1 H-NMR (d 6 -DMSO); d = 8.15? pm (d, 2H); 6.85 (d, 2H); 4.60 (m, ÍH); 4.05 (broad d, 2H); 3.75 (m, ÍH); 3.52 (t, 1H); 3.15 (t, ÍH); 2.92 (t, 2H); 2.48 (m, 6H); 2.25 (s, 2H); 1.60 (m, 8H). EXAMPLE 6 1- [2-OXO-3- (3,4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidine-3-carboxylic acid a) Analogously to example le), 550 mg of 1- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) ethyl ester - oxazolidin-5-ylmethyl] -piperidine-3-carboxylic acid is obtained as a mixture of diastereomers from 2.7 g of the l-oxiran-2-ylmethyl-piperidine-3-carboxylic acid ethyl ester (prepared from epichlorohydrin and the ethyl ester of piperidin-3-carboxylic acid analogously to example 2a)), 3.2 g amine lc) and 260 mg carbonyldiimidazole. m / e = 416. b) Analogously to example lf), 300 mg of the title compound is obtained as a light gray powder from 550 mg of the ethyl ester 6a) and 1.5 ml of the 1 n sodium hydroxide solution. m / e = 388; 1 H-NMR (d 6 -DMSO): mixture of diastereomers d = 8.15 ppm (d, 2H); 6.85 (d, 2H); 4.60 (m, 2H); 4.02 (broad d, 2H); 3.72 (m, ÍH); 3.50 (t, ÍH); 3.15 (t, ÍH); 2.90 (broad t, 3H); 2.65 (m, ÍH); 2.50 (m, 2H); 2.30-1.95 (m, 3H); 1.80-1.50 (m, 6H); 1.45-1.20 (m, 2H).

EXAMPLE 7 1- [4-Meth1-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4 acid -carboxylic a) Analogously to example Id), 14.7 g of 1- (3-methyl-oxiranyl-methyl) -piperidine-4-carboxylic acid ethyl ester is obtained as a yellow oil from 20.3 g of (rae) -transfer 2- (p-toluenesulfonyloxymethyl) -3-methyloxirane (Evans RD, Synthesis, p.862 (1988)), 13.9 ml of the ethyl ester of piperidine-4-carboxylic acid and 13.8 g of potassium carbonate in 50 ml of dimethylformamide after it is stirred for 12 hours at room temperature. ^ -NMRÍd ^ DMSO): d = 4.08 ppm (q, 2H); 2.99 (dt, ÍH); 2.90-2.65 (m, 3H); 2.55 (dd, ÍH); 2.32-2.12 (m, 2H); 2.10-1.95 (m, 2H); 1.90-1.62 (m, 4H); 1.21 (d, 3H); 1.18 (t, 3H). b) A solution of 2.5 g of the epoxide prepared in 7a), 1.0 g of sodium azide and 0.810 g of ammonium chloride is heated for 24 hours at 50 ° C in 25 ml of a mixture (80/20) water in ethanol . Subsequently the ethanol is removed in a vacuum, the residue is diluted in 10 ml of water and the aqueous solution is extracted in 3 times with 15 ml of methylene chloride each time. After the combined organic phases are dried over sodium sulfate and the solvent is removed in a rotary evaporator, the crude product is chromatographed on silica gel (isohexane in ethyl acetate: 3/1). 1.4 g of 1- (3-azido-2-hydroxy-butyl) -piperidine-4-carboxylic acid ethyl ester is obtained in this way.

^ -NMRÍCDCI: d = 4.05 ppmíq, 2H); 3.48 (m, ÍH); 2.40 (m, ÍH); 2.77-2.57 (m, 2H); 2.48 (d, ÍH); 2.35-2.08 (m, 4H); 2.02-1.55 (m, 5H); 1.20 (d and t, 5H). c) A solution of 1.4 g of the azido prepared in 7b) in 20 ml of ethanol is mixed with 0.5 g of 10% palladium carbon and the mixture is hydrogenated for 8 hours at room temperature. Then the catalyst is removed by filtration and the solution is concentrated in a rotary evaporator. 1.1 g of the l- (3-amino-2-hydroxy-butyl) -piperidine-4-carboxylic acid ethyl ester is obtained in this way. d) A solution of 1.0 g of amino 7c), 0.721 g of ketone Ib) and 1.1 g of sodium triacetateborohydride in 15 ml of methylene chloride is stirred for 15 hours at room temperature. Subsequently, the reaction mixture is mixed with 10 ml of water and acidified with IN hydrochloric acid. The phases are then separated and the aqueous acidic phase is extracted again with 10 ml of methylene chloride and then the alkali is formed with the sodium hydroxide solution. The alkaline mixture is then extracted in 3 times with 15 ml of methylene chloride each time and the combined organic phases are dried over sodium sulfate, the solvent is stirred on a rotary evaporator. The crude product is then purified by means of HPLC preparations (RP 18, methanol buffer (pH = 7.75) 70/30). In this way, 0.5 g of the 1- [2-hydroxy-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-ylamino) -butyl] ethyl ester is obtained. piperidin-4-carboxylic. ^ -NMRÍCDCI: d = 8.15 ppm (d, 2H); 6.60 (d, 2H); 4.05 (q, 2H); 3.78 (t, ÍH); 3.72 (t, ÍH); 3.58 (m, ÍH); 2.97-2.70 (m, 5H); 2.40-2.25 (m, 4H); 2.06-1.60 (m, 7H); 1.38-1.10 (m, 3H); 2.20 (t, 3H); 0.98 (d, 3H). e) A solution of 0.5 g of the aminoalcohol 7d) and 243 mg of carbonyldiimidazole in 5 ml of dimethylformamide is stirred for 24 hours at room temperature. Subsequently the reaction solution is evaporated to dryness and the residue is purified by means of HPLC preparations (Merck, Select B, methanol buffer (pH = 7.5) 65/35). 0.26 g of l- [4-methyl-2-OXO-3- (3,4,5,6-tetrahydro-2H- [1,4'] bipyridinyl-4-yl) -oxazolidin-5-ethyl ester ilmethyl] -piperidine-4-carboxylic acid is obtained in this way. M / e = 430. f) A solution of 0.26 g of the ethyl ester 7e) and 0.72 ml of the IN sodium hydroxide solution in 5 ml of methanol is stirred for 1 hour at room temperature. Subsequently the methanol is removed in a vacuum and the product is purified by means of an ion exchange (Dowex 50, form H). In this way 0.11 g of the title compound is obtained as a white powder. P.f. > 220 ° C FAB = 402. xH-NMR (d6-DMSO): d = 8.15 ppm (d, 2H); 6.80 (d, 2H); 4.55 (q, ÍH); 3.98 (m, 3H); 3.55 (t, ÍH); 2.82 (m, 4H); 2.50 (m, 8 lines, ÍH); 2.0 (m, 4H); 1.75 (m, 6H); 1.50 (broad q, 2H); 1.09 (d, 3H).

EXAMPLE 8 1- [2-oxo-3- (l-pyrimidin-4-yl-piperidin-4-yl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid a) A solution is added dropwise 18.5 g of 2,4-dichloropyrimidine in 150 ml of ethanol to a solution of 1 6 ml of 4-piperidone-ethylene ketal and 17.5 ml of triethylamine in 100 ml of ethanol while cooling on ice. Subsequently the reaction mixture is stirred for more than 2.5 hours, the ethanol is then removed in a vacuum, the residue is mixed with 100 ml of water and the aqueous mixture is extracted in 3 times with 50 ml of methylene chloride each time. After the combined organic phases are dried over sodium sulfate and the solvent is removed, the solid residue is recrystallized from isohexane in ethyl acetate. In this way 11 g of 8- (2-chloro-pyrimidin-4-yl) -1,4-dioxa-8-aza-spiro [4.5] decane is obtained as a white powder. P.f .: 135-137 ° C. b) 6 g of 2-chloropyrimidine 8a) is dissolved in 60 ml of methanol and 20 ml of tetrahydrofuran and hydrogenated for 6 hours at room temperature and 44 mbar after the addition of 4.2 g of potassium carbonate and 1 g of carbon in palladium at 10%. Subsequently, the reaction mixture is filtered, the filtrate is evaporated to dryness, the residue is taken up in 20 ml of water and the aqueous mixture is extracted in 3 times with 20 ml of methylene chloride each time. The combined organic layers are then dried over sodium sulfate and the solvent is removed 4.9 g of 8-pyrimidin-4-yl-1,4-dioxa-8-aza-spiro [4.5] decane is obtained as a white powder, m / e = 221. c) Analogously to example Ib), 3.9 g of l-pyrimidin-4-yl-piperidin-4-one is obtained as a yellow powder from 4.9 g of ketal 8b) and 60 ml of hydrochloric acid in 60 ml of tetrahydrofuran , after a reaction time of 55 hours. P.f .: 75-80 ° C. d) 8.5 g of the product is obtained analogously to example 7b) from 8 g of epoxide 2a), 3.8 g of sodium azide and 3.2 g of ammonium chloride in 100 ml of water in methanol (1/8), purification of which by means of silica gel column chromatography (0.1% methanol ammonium in acetate) yield 7.4 g (77%) of the ethyl ester of 1- (3-azido-2-hydroxy-propyl-) piperidin-4-carboxylic acid as a yellow oil. ^ -NMRÍd ^ DMSO): d = 5.01 ppm (broad s, OH, OH); 4.05 (q, 2H); 3.80 (m, ÍH); 3.20 (dddd, 2H); 2.85 (m, 2H); 2.30 (m, 3H); 2.05 (q, 2H); 1.88 (broad d, 2H); 1.55 (m, 2H); 1.12 (t, 3H). e) Analogously to example 7c), 2.9 g of 1- (3-amino-2-hydroxy-propyl) -piperidine-4-carboxylic acid ethyl ester is obtained as a viscous yellow oil, then 3.6 g of azido 8d are hydrogenated ). f) Analogously to example 7d), 1 g of 1- [2-hydroxy-3- (l-pyrimidin-4-yl-piperidin-4-ylamino) -propyl] -piperidine-4-carboxylic acid ethyl ester is obtained as a light yellow oil from 2.5 g of amine 8e), 1.9 g of ketone 8c) and 4.6 g of sodium triacetate borohydrate. xH-NMR (d6-DMSO): d = 8.49 ppm (s, ÍH); 8.15 (d, ÍH); 6.80 (d, ÍH); 4.21 (broad d, 2H); 4.05 (q, 2H); 3.61 (m, ÍH); 3. 02 (t, 2H); 2.80 (m, ÍH); 2.65 (m, 2H); 2.45 (m, ÍH); 2.24 (m, 3H); 2.00 (t, 3H); 1.88-1.68 (m, 4H); 1.57 (m, 2H); 1. 25 (t, 3H); 1.19 (m, 3H). g) Analogously to example 7e), the reaction of 1 g of aminoalcohol 8f) and 0.83 g 1,1 '-carbonyldiimidazole in 10 ml of dimethylformamide, yields of 1.2 g of the ethyl ester of 1- [2-oxo-3-] (l-Pyrimidin-4-yl-piperidin-4-yl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid as a yellow oil. FAB (MH +): 418. h) Analogously to example 7f), the saponification of 1.1 g of ethyl ester 8 g) yields of 0.61 g of the title compound as a white powder, m.p .: 145 ° C. FAB (MH +): 418. ^ -NMRÍd ^ DMSO): d = 8.22 ppm (s, ÍH); 7.90 (d, ÍH); 6.60 (d, ÍH); 4.40 (m, ÍH); 4.30 (m, 2H); 3.58 (m, ÍH); 3.31 (t, ÍH); 2.92 (m, ÍH); 2.70 (t, 3H); 2.25 (m, 3H); 1.81 (m, 3H); 1.50 (m, 4H); 1.32 (m, 4H).

EXAMPLE 9 l- acid. { 3- [1- (2-Benzylamino-pyrimidin-4-yl) -piperidin-4-yl] -2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic a) A mixture of 8 g of 8- (2-chloro-pyrimidin-4-yl) -1,4-dioxa-8-aza-spiro [4.5] decane 8a) and 7.2 ml of benzylamine is heated for 2 hours to 150 ° C, then it is cooled, mixed with 20 ml of water and the aqueous solution is extracted in 3 times with 20 ml of methylene chloride each time. The combined organic phases are then dried over sodium sulfate and the solvent is removed, the residue is washed with cold isohexane. In this way 9.6 g- of benzyl- [4- (1, 4-dioxa-8-aza-spiro [4.5] dec-8-yl) -pyrimidin-2-yl] amine is obtained as a yellow powder. 1H-MR (d6-DMSO): d = 7.85 ppm (d, ÍH); 7.40-7.18 (m, 5H); 7.15 (amlio s, ÍH, NH); 6.12 (d, ÍH); 4.45 (d, 2H); 3.96 (s, ÍH); 3.65 (m, 4H); 1.61 (m, 4H). b) Analogously to example Ib), 10.29 g l- (2-benzyl-amino-pyrimidin-4-yl) -piperidin-4-one is obtained as a chestnut powder, after a reaction time of 20 hours from 9.6 g of ketal 9a) and 85 ml of 6N hydrochloric acid in 80 ml of tetrahydrofuran mp: 98-102 ° C. c) Analogously to example 7d), 3.4 g of the ethyl ester of l- acid. { 3- [1- (2-Benzylamino-pyrimidin-4-yl) -piperidin-4-ylamino] -2-hydroxy-propyl} -piperidine-4-carboxylic acid is obtained as a yellow oil of 3.1 g of ketone 9b), 2.5 g of amine 8e) and 4.6 g of sodium triacetateborohydride. M / e = 496. 1 H-NMR (d6-DMSO): d = 7.52 ppm (d, ÍH); 7.10-6.95 (m, 5H); 6.80 (broad s, ÍH, NH); 5.80 (d, ÍH); 4.15 (d, 2H); 3.90 (m, 2H); 3.80 (q, 2H); 3.39 (m, ÍH); 3.05 (broad s, ÍH); 2.75-2.52 (m, 3H); 2.40 (m, ÍH); 2.25 (m, ÍH); 2.05 (m, 2H); 1.75 (m, 1H); 1.55 (m, 4H); 1.32 (m, 2H); 0.95 (t, 3H); 0.88 (m, 5H). d) Analogously to example 7e), the reaction of 3.4 g of aminoalcohol 9c) and 2.2 g 1,1 '-carbonyldiimidazole in 20 ml of dimethylformamide, yields of 2.3 g of the ethyl ester of l- acid. { 3- [1- (2-Benzylamino-pyrimidin-4-yl) -piperidin-4-y1] -2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxylic acid as a yellow powder. P.f .: 122 ° C. e) Analogously to example 7f), the saponification of 0.26 g of the ethyl ester 9d) yields 0.21 g of the title compound as a white powder, m.p .: 125-130 ° C. FAB (MH +): ^ -NMR (d6-DMSO): d = 7.90 ppm (d, ÍH); 7.39 (d, 2H); 7.24 (m, 3H); 6.12 (d, ÍH); 4.68 (q, ÍH); 4.51 (d, 2H); 4.45 (m, 2H); 3.85 (t, ÍH); 3.55 (t, ÍH); 3.20 (t, ÍH); 2.85 (m, 3H); 2.55 (m, 3H); 2.18 (m, 3H); 1.75 (m, 3H); 1.50 (m, 3H).

EXAMPLE 10 The following compounds are produced in an analogous manner: a) 1- [2-oxo-4-phenyl-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] - piperidin-4-carboxylic; p.f. 150 ° C (decomp.); m / e = 464. b) 1- [2-oxo-4-phenyl-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-carbonyl] - piperidinecarboxylic; p.f. 77-80 ° C; m / e = 478. c) 4-hydroxy-4- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] - cyclohexanecarboxylic; p.f. > 250 ° C; m / e = 403. d) 1- [4- (4-methoxy-phenyl) -2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin acid -5-carbonyl] -piperidine-4-carboxylic acid; p.f. 199 ° C (decomp.); m / e = 508.

EXAMPLE 11 1- [2-OXO-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-ylmethyl) -oxazolidin-5-ylmethyl] -piperidine-4-carboxylic acid a) A mixture of 4.4 g (39 mmol) 4-chloropyridine and 4.4 g (39 mmol) 4-aminomethylpiperidine is stirred for 1 hour at an oil bath temperature of 150 ° C. Subsequently the mixture is taken up in water, washed with ether, in the aqueous phase the alkaline is formed with the sodium hydroxide solution and this is extracted using dichloromethane. The extract is then dried over sodium sulfate and the solvent removed, 4.4 g (59% of theory) 3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-ylmethylamine moieties as an oil viscous. M / e = 191; ^ -NMRfCDCls): d = 8.25 ppm (d, 2H); 6.70 (d, 2H); 3.90 (d with fine resolution, 2H); 2.85 (t with fine resolution, 2H); 2.60 (d, 2H); 1.80 (m, 4H); 1.55 (m, ÍH); 1.25 (q with fine resolution, 2H). b) Analogously to example le) 1.0 g of 1- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bipyridinyl-4-ylmethyl) -oxazolidin ethyl ester -5-ylmethyl] -piperidine-4-carboxylic acid is obtained from 2.8 g of epoxide 2a), 2.6 g of amine lia) and 0.5 g of carbonyldiimidazole. m / e = 404; ^ -NMRfCDCl ^): d = 8.20 ppm (d, 2H); 6.65 (d, 2H); 4.65 (q, ÍH); 3.90 (broad d, 2H); 3.65 (m, ÍH); 3.50 (s, ÍH); 3.35 (t, ÍH); 3.15 (d, 2H); 2.85 (m, 4H); 2.60 (d, ÍH); 2.50 (m, ÍH); 2.25 (m, 2H); 1.80 (m, 8H); 1.25 (t + m, 5H). c) Analogously to the If example) 1.5 g of the title compound is obtained from 3.0 g of ethyl ester llb) and 12 ml of the sodium hydroxide solution IN as a white powder with a melting point of 94-96 ° C. . m / e = 402; 1H ~ NMR (d6-DMS0): d = 8.10 ppm (d, 2H); 6.85 (d, 2H); 4.60 (m, ÍH); 3.95 (broad d, 2H); 3.25 (dd, ÍH); 3.05 (d, 2H); 2.85 (m, 4H); 2.15 (m, 3H); 1.75 (m, 8H); 1.15 (m, 4H). EXAMPLE 12 l- acid. { 2-oxo-3- [2- (3,4,5,6-tetrahydro-2 H- [1,4 '] bipyridinyl-4-yl) -ethyl] -oxazolidin-5-ylmethyl} -piperidine-4-carboxylic a) Analogously to example lia) 5.2 g (51% theory) 2- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -ethylamine is obtained from 5.7 g 4-chloropyridine and 12.8 g 4- (2-amino-ethyl) piperidine (boiling point 100-104 ° C, prepared by hydrogenation 4- (2-amino-ethyl) pyridine [J. Amer. Chem. Soc. , 4129 (1956)] on ruthenium at 150 ° C and 150 bar of hydrogen pressure). M / e = 205; 1 H-NMR (CDC13): d = 8.20 ppm (d, 2H); 6.65 (d, 2H); 3.80 (broad d, 2H); 2.75 (m, 4H); 1.80-1.10 (m, 9H). b) Analogously to example le) 0.8 g of the ethyl ester of l- acid. { 2-Oxo-3- [2- (3, 4, 5, 6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -ethyl] -oxazolidin-5-ylmethi} -piperidine-4-carboxylic acid is obtained from 1.9 g of epoxide 2a), 5.1 g of amine 12a) and 0.5 g of carbonyldiimidazole. m / e = 444. c) Analogously to example lf) 0.4 g of the title compound is obtained as an amorphous powder from 0.7 g of the ethyl ester 12b) and 5 ml of the sodium hydroxide solution IN. m / e = 416; ^ -NMRÍCDCl,): d = 8.15 ppm (d, 2H); 6.65 (d, 2H); 4.60 (m, ÍH); 3.80 (broad d, 2H); 3.55 (t, ÍH); 3.25 (m, 2H); 2.80 (m, 6H); 2.55 (br, ÍH); 2.15 (m, 2H); 1.90-0.80 (m, 13H).

EXAMPLE 13 l- acid. { 2-Oxo-3- [1- (2-pyridin-4-yl-ethyl) -piperidin-4-yl] -oxazolidin-5-ylmethyl} -piperidine-4-carboxylic a) Analogously to Example 7b) 29 g (94% theory) of 1- (3-azido-2-hydroxy-yl) piperidine-4-carboxylic acid ethyl ester is obtained as an oil from 25.6 g of epoxide 2a) and 39 g of sodium azide. M / e = 256. b) Analogously to example 7c) 21.1 g (81% theory) of the ethyl ester of acid 1- (3-azido-2-hydroxy-propyl) piperidine-4-carboxylic acid is obtained by catalytic reduction from 29 g of the azido 13a). M / e = 230; xH-NMR (CDClt): d = 4.15 ppm (q, 2H); 3.65 (m, ÍH); 2.95 (m, ÍH); 2.80 (dd, 2H); 2.65 (dd, ÍH); 2.30 (m, 7H); 2.05-1.65 (m, 4H); 1.25 (t, 3H). c) A solution of 16.2 ml (150 mmol) of 4-vinylpyridine in 5.7 ml of glacial acetic acid is mixed with 12.8 ml of the ketal 4-piperidone-ethylene and heated for 3 hours at 100 ° C. Subsequently, the reaction mixture forms an alkaline with the 2N sodium hydroxide solution, is stirred for 15 minutes at room temperature and then mixed with the sodium hydroxide solution ION in order to remove the base. This is extracted with dichloromethane, dried over sodium sulfate, evaporated in a vacuum and chromatographed on silica gel. 16.3 g (66% theory) 8- (2-pyridin-4-yl-methyl) -1,4-dioxa-8-aza-spiro [4, 5] decane is eluted using ethyl acetate in isohexane 3: 1 . LH-NMR (CDC13): d = 8.50 ppm (d, 2H); 7.15 (d, 2H); 3.95 (s, 4H); 2.75 (m, 2H); 2.55 (m, 6H); 1.75 (dd, 4H). d) Analogously to example Ib) 10.2 g (100% theory) 1- (2-pyridin-4-yl-ethyl) -piperidin-4-one is obtained as an oil from 12.4 g of ketal 13c). ^ -NMRÍCDCI: d = 8.50 ppm (d, 2H); 7.15 (d, 2H); 2.75 (m, 8H); 2.45 (t, 4H). e) Analogously to Example 7d) 0.9 g of the ethyl ester of l- acid. { 2-hydroxy-3- [1- (2-pyridin-4-yl-ethyl) piperidin-4-ylamino] propi} -piperidine-4-carboxylic acid is obtained as an oil from 2.1 g of amine 13b) and 1.9 g of ketone 13d). HL-N RÍCDCl,): d = 8.50 ppm (d, 2H); 7.15 (d, 2H); 4.10 (q, 2H); 3.80 (m, ÍH); 2.90 (m, 4H); 2.75 (m, 4H); 2.55 (m, 4H); 2.30 (m, 4H); 2.05 (m, 2H); 1.85 (br, d, 4H); 1.75 (m, 2H); 1.40 (m, 2H); 1.25 (t, 3H). f) Analogously to example 7e) 1.7 g of the ethyl ester of l- acid. { 2-Oxo-3- [1- (2-pyridin-4-yl-ethyl) -piperidin-4-yl] -oxazolidin-5-ylmethyl} -piperidine-4-carboxylic acid is obtained as an oil from 2.6 g of aminoalcohol 13e) and 1.3 g carbonyldiimidazole. m / e = 444; 1 H-NMR (CDC13): d = 8.50 ppm (d, 2H); 7.15 (d, 2H); 4.60 (m, ÍH); 4.15 (q, 2H); 3.70 (m, ÍH); 3.55 (t, ÍH); 3.30 (t, ÍH); 3.05 (br, d, 2H); 2.80 (m, 4H); 2.60 (m, 4H); 2.20 (m, 5H); 1.80 (m, 8H); 1.25 (t, 3H). g) Analogously to example lf) 1.2 g (75% theory) of the title compound is obtained as an amorphous powder from 1.7 g of the ethyl ester 13f) and 5.2 g of the sodium hydroxide solution IN. m / e = 416; ^ -NMRÍCDCI: d = 8.20 ppm (d, 2H); 7.05 (d, 2H); 4.40 (br, t, ÍH); 3.30 (m, 2H); 2.95 (t, ÍH); 2.75 (br, d, 2H); 2.55 (m, 4H); 2.25 (m, 4H); 1.80 (m, 5H); 1.55 (m, 2H); 1.35 (m, 6H).

EXAMPLE 14 PHARMACEUTICAL DATA TEST The microtitre plates are cooled at night with the Illa receptor and GpIIb in isolated activity of 2μg / ml. After the unveiled receiver has been removed by several washing steps, the surface of the plate is blocked with 1% concasein and again washed. Substantial test is added to the necessary concentrations, the dishes are subsequently incubated for 10 minutes while shaking in a linear trill. The natural ligand of the fibrinogen receptor of Illa and GpIIb is added thereto. After incubation for 1 hour, the unbound fibrinogen is removed by several washing steps and the bound fibrinogen is determined in an ELISA anthology to determine the change in optical density at 405 nm caused by a peroxidase conjugated monoclonal antibody. The inhibition of driving the Illa and GpIIb interaction of fibrinogen for low optical densities. The IC50 value is determined by means of an effect-concentration curve.

LITERATURE The fibrinogen Illa and GpIIb of ELISA is a modification of the assay which is described in the following references: Nachman, R.L. & Leung, L.L.K. (1982): complex formation of platelet membrane glycoproteins lib and Illa with fibrinogen. J. Clin. Invest. 69: 263-269. right, P. S. - et al. (1983); An echistatin of the ligand Illa and GpIIb of the C-terminal activated peptide for fibrinogen, fibronectin, vitronectin and collagen type I and type IV. Biochem. J. 293: 262-267. i n TABLE: It is noted that in relation to this date, the method known to the applicant to carry out the aforementioned invention is the clear result of the present description of the invention.

Having described the invention as above, the content of the following is claimed as property.

Claims (5)

1. - The compounds of the general formula I, X, Y and Q independently denote a hydrogen or CH W denotes a hydrogen or NR ° R00 Z denotes a hydrogen, CH or C-OH A, E and G independently denote a valence break or an alkylene chain - (CH2) n B denotes a valence break and also denotes a carbonyl group in the case where Z is equal to ND denotes a side chain in the form of - (CHR3) m -COO- or = CR3-C00- n denotes 1-5 m denotes 0, 1 R1, R2 independently denotes a hydrogen, lower alkyl or aryl or together they form a 5-membered or 6-membered carboxylic ring, R3 denotes a hydrogen or a group -OR5 or -NR6R7 R4 denotes a hydrogen or a group -OR5 R5 denotes a hydrogen, lower alkyl, aryl or arylalkyl Rb denotes a hydrogen, lower alkyl or arylalkyl R7 denotes a hydrogen, lower alkyl, arylalkyl, acyl, alkylsulfonyl or arylsulfonyl R °, R00 independently denotes a hydrogen, lower alkyl, aryl, arylalkyl , hetaryl, acyl or an optionally substituted heterocyclic or carboxylic ring or, together with the hydrogen to which they are attached, they form a 5-membered or optionally substituted 6-membered ring which may in addition contain more than 1 to 3 heteroatoms or denote a group Rooo I -C-NH R000 denotes a hydrogen, lower alkyl, arylalkyl or a group NHR0000 R0000 denotes a hydrogen, lower alkyl, arylalkyl, aciio, alkylsulfonyl or arylsulfonyl as well as their conformational isomers and pharmaceutically acceptable salts thereof.

2. The compounds of the general formula I according to claim 1, characterized in that n has a value of 1.2 or 3.

3. - The compounds l- [(5S) -2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-iimethyl] - piperidin-4-carboxylic l- [(rac) -2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4 acid -carboxylic acid { 1- [(Rao) -2-OXO-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidine-4- ilideno} -acetic acid { 4-hydroxy-l- [2-oxo-3- (3, 4, 5, 6-tetrahydro-2H- [1,4'] ipiridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4- il-acetic acid 1- [4-methyl-2-oxo-3- (3,, 5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin -4-carboxylic 1- [2-Oxo-4-phenyl-3- (3, 4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4 acid -carboxylic 1- [2-Oxo-3- (l-pyridin-4-yl-piperazin-4-yl) -oxazolidin-5-ylmethyl) -piperidine-4-carboxylic acid l- acid. { 3- [2-benzylamino-pyrimidin-4-yl) -piperidin-4-yl] -2-oxo-oxazolidin-5-ylmethyl} -piperidine-4-carboxyl 1- [2-Oxo-4-phenyl-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin-4 acid -carboxyl 4-hydroxy-4- [2-oxo-3- (3,4,5,6-tetrahydro-2H- [1, 4 '] bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -cielohexanecarboxylic acid ( 5S) -1- [5-methyl-2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4'-bipyridinyl-4-yl) -oxazolidin-5-ylmethyl] -piperidin- 4-carboxylic 1- [2-OXO-3- (3, 4, 5, 6-tetrahydro-2H- [1,4 '] bi? iridinyl-4-yl) -4- (3-trifluoromethyl-1-phenyl) -oxazolidin- 5-ylmethyl] -piperidine-4-carboxylic acid 1- [4- (4-chloro-phenyl) -2-oxo-3- (3,4,5,6-tetrahydro-2H- [1,4 '] bipyridinyl-4-yl) -oxazolidin-5-acid ilmethyl] -piperidine- -carboxylic acid as well as their conformational isomers and the pharmaceutically acceptable salts thereof.

4. - Pharmaceutical composition containing at least one compound according to formula I as claimed in one of claims 1-3 in addition to common carriers and excipients.

5. The use of substances according to one of claims 1-3, characterized for the production of pharmaceutical agents for the treatment of diseases which is due to an aggregation of platelets in the body.