Derivatives of oxazolidine, the method of production thereof, and pharmaceutical composition

 

(57) Abstract:

Describes new derivatives of oxazolidine General formula I, where R1denotes X represents O; Y represents substituted with R2pieperazinove balance; In denotes H, A, AG-CkH2kor amidinopropane; R2denotes-CrH2r-COOR3; R3denotes H, a or benzyl; And denotes alkyl with 1 to 6 C-atoms; AG denotes phenyl; k represents 0, 1, 2, 3 or 4; m represents 0; r represents 0, 1 or 2, as well as their physiologically acceptable salts. The compounds exhibit anti-tumor activity, also suitable as antimicrobial biologically active substances. Also exhibit properties of inhibitors of the binding of fibrinogen. Describes the retrieval method and farmcampsite on the basis of the compounds of formula I. 3 S. and 2 C.p. f-crystals, 1 PL.

The invention relates to compounds of formula I:

< / BR>
where X denotes O, S, NH or NA;

Y represents substituted with R2aziridinyl, azetidinone, pyrolidine, piperidinyl, hexahydroazepin or pieperazinove the rest;

R1indicates or

R2represents CrH2r-COOR3;

R3denotes H, A is - or aydinbey the rest;

Ar denotes unsubstituted or mono - or twice substituted with A, Cl, Br, I, NO2, CN, OA, OH, NH2, NHA and/or NA2phenyl or benzyl residue;

"k" denotes 1, 2, 3 or 4;

"m" and "r" each, independently of one another, denote 0, 1, 2, 3 or 4; and

"n" represents 2, 3 or 4,

and their physiologically acceptable salts.

Similar compounds are known from European patent EP-A1-0 381033.

The basis of the invention is to obtain new compounds with valuable properties, in particular, those that can be used for the preparation of drugs.

This problem is solved by the present invention. It was found that the compounds of formula (I), and their solvate and salt, with good compatibility possess valuable pharmacological properties. In particular, they inhibit the binding of fibrinogen, fibronectin and von Willebrand factor with fibrinogenesis receptor of blood platelets (glycoprotein IIb/IIIa), as well as linking them and other adhesive proteins, such as vitronectin, collagen and laminin, to the corresponding receptors on the surface of various cell types. The compounds thus have an impact on the interaction between cell-cell and cell-Matrena thrombosis, apoplexy, heart attack, ischemia, inflammation, arteriosclerosis and acute renal nedostatochnosty. Further, the compounds have an impact on tumor cells because they inhibit metastasis. Thus they can also be used as anticancer agents.

It is shown that tumor cells into the blood vessels due to microthrombi and thus protected from recognition by cells of the immune system. Similarly, microthrombi promote the binding of tumor cells to blood vessel walls. Since the formation of microthrombi associated with the binding of fibrinogen with fibrinogenesis receptor (glycoprotein IIb/IIIa inhibitors), inhibitors of the binding of fibrinogen have value as inhibitors of metastasis.

Moreover, compounds suitable as antimicrobial biologically active substances, which can prevent infections caused by, for example, bacteria, fungi or yeast. Therefore, substances can act (behave) as related antimicrobial bioactive substances when carried out interventions in the organisms which use foreign substances, as, for example, biomaterials, implants, catheters or electrostatic damage to the module can be detected for example, according to the method of P. Valentin-Weigand and others described in Infection and Immunity, 2851 - 2855 (1988).

Other properties of the compounds can be detected by the methods described in the European patent EP-A1-0462960. Inhibition of binding of fibrinogen with fibrinogenesis receptor can be detected by the method specified in European patent EP-A1-0381033. The vast platelet aggregation effect can be detected in vitro by the method of born (Nature, 4832, 927 - 929, 1962).

The subject invention further is a method for obtaining compounds of the indicated formula (I) and its salts, characterized in that:

(a) compound of formula (I) release from one of its functional derivatives by treatment with solvolysis or hydrogenolysis funds; or

(b) a compound of the formula (II):

< / BR>
where Z denotes chlorine, bromine, iodine or reactive, esterified ester to OH-group; and

R1and X have the above values,

enter into interaction with the compound of the formula (III): H-Y (III), where Y is the specified value; or

(C) a compound of the formula (IV): R1-NH-CH2-CH(XH)-CH2-Y (IV) wherein R1X and Y have the above values, enter into interaction with Regazzoni values

enter into interaction with the compound of the formula (VI):

(VI)

where B is the specified value and L denotes or and

Z' represents chlorine, bromine, iodine, OA, OH or a reactive, esterified to ester, an OH group, respectively, it is easy nucleophile replaced the deleted group; or

(d) residue (remainder) R1and/or Y-turn in the remainder (other remains) R1and/or Y; and/or

(e) compound of formula (I) by treatment with acid or base is translated into one of its salts.

The compounds of formula (I) possess at least one chiral center and therefore can be in several enantiomeric forms. All of these forms (for example, D - and L-forms) and their mixtures (for example, DL-forms) are covered by formula (I).

Above and specified below, remains of, respectively, the parameters A, B, L, X, Y, Z, Z', R1R3, Ar, "k", "m", "n" and "r" are specified in the case of formulas (I) - (VI) values, unless nothing else. If there are several equally marked groups in the molecule, they are, independently from each other, can have different values.

In the above formulas A group contains 1 to 6, preferably 1, 2, 3 or 4 C-atoms. Frequent; the button also pencil; 1-, 2 - or 3-methylbutyl; 1,1-, 1,2 - or 2,2-dimethylpropyl; 1-ethylpropyl; hexyl; 1-, 2-, 3 - or 4-methylpentyl.

R1preferably represents 4-piperidinyl, 1-benzyl-4-piperidinyl, 4-piperidinylmethyl, 4-piperidylamine, 1-amidino-4-piperidinyl, 1-amidino-4-piperidinylmethyl, 4-piperazinylmethyl, 4-piperazinylmethyl, 4-piperazinil boutigny, 1-amidino-4-piperazinylmethyl or 1-amidino-4-piperazinylmethyl the rest.

R2preferably represents -(CH2)2-COOR3, -(CH2)3-COOR3or-CH2-COOR3and R3preferably represents hydrogen, methyl, ethyl or benzyl.

Ar preferably denotes unsubstituted benzyl.

X preferably represents oxygen.

Y preferably denotes piperazinil or piperidyl.

The parameters "k" and "m" preferably denotes 0 or 1. The parameter "n" preferably denotes 2 or 3, and the parameter "r" preferably denotes 1, 2 or 3.

Of the compounds of formula (I) are preferred those in which at least one of these residues, groups, and/or parameters is one of these preferred values. Some gr), however, where:

in Ia: X represents oxygen, a R1denotes 4-piperidyl;

in Ib: X is oxygen, and R1denotes 1-amidino-4-piperidyl;

Ic: X is oxygen, and R1denotes 1-benzyl-4-piperidyl;

in Id: X is oxygen, and R1denotes 4-piperidinyl, -ethyl or-propyl;

Ie: X is oxygen, and R1denotes 1-amidino-4 - piperidinyl, -ethyl or-propyl;

If: X is oxygen, and R1denotes 1-benzyl-4 - piperidinyl, -ethyl or-propyl;

in Ig: X is oxygen, and R1denotes 1-piperazinylmethyl, 1-amidino-4-piperazinyl or 1-benzyl-4-piperazinylmethyl;

in Ih: X is oxygen, and R1denotes 1-piperazinylmethyl, 1-amidino-4-piperazinyl or 1-benzyl-4-piperazinylmethyl.

Further, preferred compounds of formula (Ii), and (Iai) - (Ihi), which correspond to the formula (I), respectively, (Ia) - (Ih), where, however, more

Y denotes a 3-R2-azetidine-, 2-R2-pyrrolidino-, 2-R2-piperidino-, 3 -, R2- piperidino-, 4 -, R2-piperidino-, 4 -, R2-piperazine derivatives or 3-R2-piperazinone; and

R2means-COOR3, -CH2COOR3, -(CH2)2the receipt, get itself known methods, which are described in the literature (for example, in the Handbook as Houben-Weil, Methods of organic chemistry, ed. Georg-Thieme, Stuttgart; further, European patent EP-A1-0381033; European patent EP-A1-0462960), namely under reaction conditions which are known and suitable for the specified transformations. You can also use themselves known here more not mentioned options.

The source of the substance, if desired, can also be obtained in situ, so they are not isolated from the reaction mixture, and immediately injected into the interaction further, to obtain the compounds of formula (I).

The compounds of formula (I) can be obtained by the fact that their release from their functional derivatives by solvolysis, in particular hydrolysis, or by hydrogenolysis.

The preferred initial agents for the solvolysis, respectively, hydrolysis, are such that typically correspond to the formula (I), however, instead of one or more free amino and/or hydroxyl groups contain protected amino and/or hydroxyl groups, preferably such that instead of H-atom with a N-atom, contain protective for amino function group, pH is such which, instead of the H atom of the hydroxyl group containing protective for hydroxyl function group, for example, those that correspond to the formula (I), however, instead of the group-COOH contain a group-COOR", where R ' denotes a hydroxyl protective for the function group.

In the molecule of the original substance can be several identical or different protected amino and/or hydroxyl groups. If the existing protective group different from each other, but in many cases they can be selectively split.

The expression "protection for the amino function group" is well known and relates to groups which are suitable for protecting (blocking) amino group from chemical reactions but which, however, can be easily removed after elsewhere molecules was desired chemical reaction. Typical of such groups are especially unsubstituted or substituted acyl, aryl (for example, 2,4-dinitrophenyl [DNP]), arelaxation (for example, benzoyloxymethyl [BOM] ) or kalkilya group (for example, benzyl, 4-nitrobenzyl, triphenylmethyl). As protective for the amino function groups are removed after the desired reaction (or sequence of reactions), their race and size are not to the"acyl group" in connection with the present method should be understood in its broadest sense. It includes produced from aliphatic, alifaticheskih, aromatic or heterocyclic carboxylic acids or sulfonic acids acyl group, and in particular alkoxycarbonyl, aryloxyalkyl and primarily alcoxycarbenium group. Examples of such acyl groups are alkanoyl as acetyl, propionyl, butyryl; arcanol as phenylacetyl; aroyl as benzoyl or toluyl; aryloxyalkanoic as phenoxyacetyl; alkoxycarbonyl as methoxycarbonyl, etoxycarbonyl, 2,2,2-trichlorocyanuric, isopropoxycarbonyl, tert. -butoxycarbonyl (BOC), 2-iodoxybenzoic; Uralelectromed as benzyloxycarbonyl (CBZ), 4-methoxybenzeneboronic, 9-fluorenylmethoxycarbonyl (FMOC). Preferred protective for amino function groups are BOC, DNP and BOM, then, CBZ, benzyl and acetyl.

The expression "hydroxyl protective for function group" is also generally known and relates to groups which are suitable for protecting a hydroxyl group from chemical reactions but which, however, can be easily removed after elsewhere molecules was desired chemical reaction. Typical of such groups are the abovementioned unsubstituted or substituted oreiley group functionality is not critical, as they again removed after the desired chemical reaction or sequence of reactions; preferred group with 1 to 20, particularly 1 to 10 C-atoms. Examples of hydroxyl protective for function groups are, inter alia, tert.-butyl, benzyl, p-nitrobenzoyl, p-toluensulfonyl and acetyl, and especially preferred benzyl and acetyl.

Used as starting substances, the functional derivatives of compounds of formula (I) can be obtained by conventional means, which are described, for example, specified in the standard works and patent applications, for example, by reacting compounds which correspond to formula (II) and (III), whereby, however, at least one of these compounds contains a protective group instead of the H atom.

The release of the compounds of formula I from their functional derivatives is carried out, depending on the protective group, for example using strong acids, expediently using triperoxonane acid or perchloric acid, but also using other strong inorganic acids as hydrochloric acid or sulfuric acid, strong organic carboxylic acids, as trichloroacetic acid, or sulfonic acids, as benzene - alphademo.

As the inert solvent is preferably suitable organic, for example carboxylic acids, as acetic acid; ethers, like tetrahydrofuran or dioxane; amides as dimethylformamide (DMF); halogenated hydrocarbons like dichloromethane; sulfoxidov as dimethyl sulfoxide (DMSO); hereinafter, also alcohols as methanol, ethanol or isopropanol, and also water. Next, apply a mixture of the above solvents.

Triperoxonane acid is preferably used in excess without addition of a solvent; perchloric acid is used in the form of a mixture of acetic acid and 70% perchloric acid in the ratio 9:1. The reaction temperature for the expedient removal of approximately 0 to 50oC; preferably operate at 15 - 30oC (room temperature).

BOC group can preferably be split, for example, with 40% triperoxonane acid in dichloromethane or using approximately 3 to 5N. HCl in dioxane at 15 - 60oC; FMOC-group with about 5 to 20% solution of dimethylamine, diethylamine or piperidine in DMF at 15 - 50oC. Removal of DNP-groups are, for example, also using about 3 - 10%-aqueous solution of 2-mercaptoethanol in a mixture of DMF with water when 1 is set, for example, by treatment with hydrogen in the presence of a catalyst (for example, a catalyst based on a noble metal, such as palladium, expediently on the media, as coal). As solvents suitable for this above, in particular, for example, alcohols, like methanol or ethanol, or amides, as DMF. The hydrogenolysis is carried out, as a rule, at temperatures of about 0 - 100oC and pressures of about 1 to 200 bar, preferably at 20 to 30oC and pressure 1 - 10 bar. Hydrogenolysis of CBZ-group flows well, for example, in the presence of 5 - 10% Pd-C in methanol at 20 - 30oC.

The compounds of formula (I) can be obtained preferably by the interaction of the compounds of formula (II) with a base of formula (III). It is reasonable to use themselves known methods for N-alkylation.

Remove the group Z preferably denotes Cl, Br, I; C1-C6-alkylsulfonates, such as methane - or econsultancy; or C6-C10-arylsulfonate as benzene-, p-toluene - or 1 - or 2-naphthalenesulfonate.

The reaction is carried out preferably in the presence of an additional base, such as hydroxide of alkali or deletetime is I; carbonate of sodium, potassium or calcium, in an inert solvent, for example, in a halogenated hydrocarbon like dichloromethane; simple ether as THF or dioxane; amide as DMF or dimethylacetamide; nitrile as acetonitrile; at temperatures from about -10oC to 200oC, preferably at 0 to 120oC. if the deleted group Z is different from I, it is recommended that the addition of iodide as the potassium iodide.

Educt of the formula (II), as a rule, are new. They can be obtained, for example, by reacting substituted derivative of piperidine or piperazine of the formula R1-NH2with the compound of the formula R5CH2-CHR6-CH2HE (where R5= Z; R6= XR7and R7denotes a protective group; R5and R6together also denote oxygen) to produce the compounds of formula R1-NH-CH2-CHR8-CH2OH (where R8= XR7or OH), if necessary, removal of the protective group R7to obtain compounds of the formula R1-NH-CH2-CH(XH)-CH2OH, interaction with a derivative of carbonic acid, as diethylcarbamyl, with 3 R1-5-hydroxymethyl-2-oxazolidinones and turning hydroxymethylene group in CH2Z formula H-Y (III), generally known or get them by analogy with known compounds.

The compounds of formula (I), below, can be obtained by reacting the compounds of formula (IV) or its reactive derivative) with a reactive derivative of carbonic acid.

As a derivative of carbonic acid in particular suitable diallylmalonate as diethylcarbamyl further complicated alkalemia esters of Harborview acid, as ethylchloride. A derivative of carbonic acid, which is suitable used in excess, preferably also serves as a solvent, preferably, a suspending agent. However, you may also attend one of these solvents, if it is inert in this interaction. Further, it is recommended to add the base, especially alcoholate of alkali metal tert.-butyl potassium. It is advisable operate at reaction temperatures of 0 - 150oC, preferably at 70 - 120oC.

Educt of the formula (IV) are new. Get them, for example, by functionalization of the above compounds of formula R1-NH-CH2-CH(XH)-CH2OH obtaining compounds of formula R1-NH-CHthe e R1denotes 1-amidino-piperidinol or piperazinilnom group corresponding piperidine or piperazinovogo connection can handle lidiruyushchim agent. As ameerega agent preferred 1-amidino-3,5-dimethylpyrazole, which is particularly used in the form of its nitrate. It is advisable to work with the addition of a base as triethylamine or ethyldiethanolamine, in an inert solvent or mixture of solvents, e.g. a mixture of water with dioxane, at temperatures of 0 - 120oC, preferably 60 to 120oC.

Further, the compound of formula (I) can be obtained by the fact that the compound of formula (V) enter into interaction with piperidinium or piperazinone derivative of the formula (VI).

The compounds of formula (V) can be obtained by reacting the compounds of formula H2N-CH2-CH(XH)-CH2Y, where X and Y have the above meanings, with a reactive derivative of carbonic acid. The reaction conditions and suitable derivatives of carbonic acid correspond to the above.

The compounds of formula (VI) are generally known or can be obtained in itself known methods; connection with BH, for example, can be obtained by functionalization sootvetstvenno to make itself known methods N-alkylation of amines, in particular, cyclic amines, which are described above for compounds of formula (II) and formula (III).

Further, in the compound of formula (I) one or both of the remainder R1and/or Y can be transformed into another residue (other remains) R1and/or y

In particular, you can atrificial to carboxyl ester group, to split the ester group, hydrogenations to remove the benzyl group or treated with amino groups using ameerega agent. Next, you can enter or to split the usual protective for amino functions or hydroxy functions of the group.

For the esterification to complex ester, an acid of the formula (I) (R3= H) can be treated with excess alcohol of formula R3OH (R3= A or benzyl), expediently in the presence of a strong acid like hydrochloric acid or sulfuric acid, at temperatures of 0 - 100oC, preferably 20 - 50oC.

On the contrary, an ester of formula (I) (R3= A or benzyl) can be transformed into the corresponding acid of formula (I) (R3= H), it is by solvolysis one of the above methods, for example, using NaOH or KOH in a mixture of water with dioxane at temperatures 0 - 40oC, preferably 10 - 30oC. slots. For this transformation, in particular taking into account the acid, which give physiologically acceptable salts. Thus, it is possible to use inorganic acids, for example sulfuric acid, nitric acid, halogen acids as hydrochloric acid or Hydrobromic acid, phosphoric acid, like phosphoric acid; sulfamic acid; further, organic acids, in particular aliphatic, alicyclic, analiticheskie, aromatic or heterocyclic one - or polybasic carboxylic, sulfonic or sulfuric acids, such as formic acid, acetic acid, triperoxonane acid, propionic acid, pavlikova acid, diethyloxalate acid, malonic acid, succinic acid, Emelyanova acid, fumaric acid, maleic acid, lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinamide acid, methane - or econsultation, ethicalfashion, 2-hydroxyethanesulfonic, benzosulfimide, p-toluensulfonate, naphthalene mono - and di-sulfonic acids, louisanna acid. Salts with physiologically unacceptable acids, for example, picrate, moeli preferably, you can release from their salts by treatment with strong bases like sodium hydroxide or potassium hydroxide, sodium carbonate or potassium.

You can also carboxylic acids of the formula (I) (R3= H) by entering into cooperation with the relevant reason to turn in their metal salts or ammonium, for example, their sodium, potassium or calcium salt.

The compounds of formula (I) contain one or more chiral centers and therefore may exist in racemic or optically active form. Resulting racemates can be separated into the enantiomers according itself known methods of chemically or mechanically. Preferably, from the racemic mixture by introducing into interaction with optically active separating means are formed diastereomers. As release agents are suitable, for example, optically active acids, such as D - and L-forms of tartaric acid, diatsetilvinny acid, dibenzoyltartaric acid, almond acid, malic acid, lactic acid or the various optically active camphorsulfonic as camphorsulfonate. The separation of enantiomers is also preferable to carry out filled with optically active divide the example, a mixture of hexane with isopropanol and acetonitrile, for example, in a volume ratio 82:15:3.

Naturally, it is also possible to obtain optically active compounds of formula (I) according to the above methods, because they use the original substance (for example, those of formula (II)), which are already optically active.

The new compounds of formula (I) and their physiologically acceptable salts can be used for the preparation of pharmaceutical preparations, the fact that it, together with at least one carrier or auxiliary substance and, if desirable, together with one or more other biologically active substances brought to a suitable dosage forms. The thus obtained composition can be used as a drug in human or veterinary medicine, as carriers take into account organic or inorganic substances which are suitable for intestinal (e.g., oral or rectal) or parenteral administration or for administration in the form of an inhalation spray and do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate and other glycerides of fatty acids, as the change are particularly tablets, tablets, capsules, syrups, juices or drops, are of special interest lacquered tablets and capsules resistant to gastric juice coatings, respectively, the shells of the capsules. For rectal use suppositories, for parenteral use, solutions, preferably oily or aqueous solutions, furthermore, suspensions, emulsions or implants.

For use as an inhalation spray, apply the sprays that contain biologically active compound either dissolved or suspended in a mixture of working gases. This biologically active substance suitable used in micronized form, and can be added one or more additional physiologically acceptable solvents, such as ethanol. Solutions for inhalation can be entered using a conventional inhalers. The new compounds can also be liofilizirovanny and received lyophilizate can be applied, for example, for the preparation of drugs for injection. These compositions can be sterilized and/or they may contain auxiliary substances, such as preservatives, stabilizers and/or wetting, emulsifying agents, salts for influencing osmotic d is the train one or more other biologically active substances, for example, one or more vitamins.

Proposed according to the invention substances normally administered analogously to other known being sold as a pharmaceutical, in particular, however, similar to the one described in European patent EP-A-459256 compounds, preferably at doses of about 5 mg to 1 g, particularly 50 to 500 mg, dosing unit. The daily dose is preferably about 0.1 - 20 mg/kg, in particular 1 to 10 mg/kg of body weight. Special dose for each particular patient, however, depends on various factors, for example, the effectiveness of used special compound, the age, body weight, General health, sex, cost, time and route of administration, rate of excretion, combination of drugs and the severity of the respective disease, which has implications for therapy. Preferably oral administration.

Above and below, all temperatures are given inoC. In the following examples, the expression "conventional treatment" means: "add, if necessary, water; depending on the structure of the target product set pH = 2 to 8; filtered through the ion exchanger; separating; silicagel and/or by crystallization.

EXAMPLE 1

To a solution of 1.6 g of methyl ester of 3-piperazine derivatives-propanoic acid ("A") [produced by interaction of the methyl ester 3 - chloropropanol acid with piperazine] in 20 ml of DMF added 3.0 g of 3-(1-BOC-4-piperidyl)-5-methanesulfonylaminoethyl-2-it [produced by interaction of 1-BOC-4-amino-piperidine with 2,3-epoxypropan-1-one to obtain 4-(2,3-dihydroxy-propylamino)-piperidine, introduction, in cooperation with diethylmalonate in the presence of tert. -butyl potassium 3-(1-BOC-4-piperidyl)-5-hydroxymethyl-oxazolidin-2-it and subsequent esterification to complex ester with methanesulfonamido] , dissolved in 10 ml of DMF, and stirred for 60 minutes at room temperature. After removal of the solvent and the normal processing gain 3-(1-BOC-4-piperidyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives] -methyloxazolidine-2-it.

Similarly, by reacting an "A"

with 3-(1-benzyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-benzyl-4-piperidyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives] -methyl-oxazolidin-2-it, so pl. 86 - 87oC;

with 3-(1-N-BOC-amidino-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-N-BOC-amidino-4-piperidyl)-5-[4-(2-methoxycarbonylethyl the-2-one obtained 3-(1-benzyl-4-piperidinylmethyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-benzyl-4-piperidyl)-ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-benzyl-4-piperidyl)ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyl oxazolidin-2-he;

with 3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-benzyl-4-piperidyl)-propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperidyl)propyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-N-BOC-amidino-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-N-BOC-amidino-4-piperidyl)propyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperidyl)-butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-benzyl-4-piperidyl)butyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-on the floor-[2-(1-benzyl-4-piperazinil)-ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-benzyl-4-piperazinil)-ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-N-BOC-amidino-4-piperazinil)-ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-N-BOC-amidino-4-piperazinil)-ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-benzyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperazinil)propyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-methane-sulfonylacetanilide-2-one obtained 3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-benzyl-4-piperazinil)butyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-N-BOC-amidino-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-N-BOC-amidino-4-piperazinil)-butyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-methyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-methyl-4-piperidyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-isopropyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-on poluchil-4-piperidinyl-methyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-tert. -butyl-4-piperidinylmethyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-ethyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-ethyl-4-piperidinylmethyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-isopropyl-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-isopropyl-4-piperidyl)-ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-cyclohexyl-4-piperidyl)-ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-cyclohexyl-4-piperidyl)ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-methyl-4-piperidyl)-propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-methyl-4-piperidyl)-propyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-cyclopentyl-4-piperidyl)-propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-cyclopentyl-4-piperidyl)propyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-tert. -butyl-4-piperidyl)-butyl]-5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-tert.-butyl-4-piperidyl)-butyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-sapropel-4-piperidyl)-butyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-methyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-methyl-4-piperazinil)ethyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyl oxazolidin-2-he;

with 3-[2-(1-cyclopropyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-cyclopropyl-4-piperazinil)ethyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-ethyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-ethyl-4-piperazinil)propyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-isopropyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-isopropyl-4-piperazinil)propyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-propyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-propyl-4-piperazinil)butyl]-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-it.

EXAMPLE 2

Analogously to example 1, by usaimage climatisation-2-get it 3-(1-benzyl-4-piperidyl)-5-[4-(2-benzyloxycarbonylamino)-piperazine derivatives]-methyloxazolidine-2-he is so pl. 91 - 92oC.

Similarly, through the interaction of a "B"

with 3-(1-benzyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-benzyl-4-piperidinylmethyl)-5-[4-(2-benzyloxycarbonylamino)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-benzyl-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-benzyl-4-piperidyl) ethyl]-5-[4-(2-benzyloxycarbonylamino)-piperazine derivatives]-methyl oxazolidin-2-he;

with 3-[3-(1-benzyl-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperidyl)propyl]-5-[4-(2-benzyloxycarbonylamino)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-benzyl-4-piperidyl)butyl] -5-[4-(2-benzyloxycarbonylamino)-piperazine derivatives]-methyloxazolidine-2-it.

EXAMPLE 3

Analogously to example 1, from methyl ester 2-piperazinone acid [obtained by interaction of the methyl ester-Chloroacetic acid with piperazine], by introducing it into an interaction with 3-(1-BOC-4-piperidyl)-5-methanesulfonylaminoethyl-2-one, after conventional treatment, a 3-(1-BOC-4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives] -methyloxan the s

with 3-(1-benzyl-4-piperidyl)-5-methanesulfonylaminoethyl - 2-one obtained 3-(1-benzyl-4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-N-BOC-amidino-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-N-BOC-amidino-4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-benzyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-benzyl-4-piperidinylmethyl)- 5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-benzyl-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-benzyl-4-piperidyl)ethyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-benzyl-4-piperidyl) propyl]-5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperidyl)propyl]-5-[4-(metallokonstrukstij-2-one obtained 3-[3-(1-N-BOC-amidino-4-piperidyl)propyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-benzyl-4-piperidyl)butyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-benzyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-benzyl-4-piperazinil)ethyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-N-BOC-amidino-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-N-BOC-amidino-4-piperazinil)ethyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-benzyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperazinil)propyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-methane-sulfonylacetanilide-2-one obtained 3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl the one-2-he;

with 3-[4-(1-N-BOC-amidino-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-N-BOC-amidino-4-piperazinil)butyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-methyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-methyl-4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives] -methyloxazolidine-2-he;

with 3-(1-isopropyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-isopropyl-4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-tert. -butyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-tert.-butyl-4-piperidinylmethyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-ethyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-ethyl-4-piperidinylmethyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-isopropyl-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-isopropyl-4-piperidyl)ethyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-cyclohexyl-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-cyclohexyl-4-piperidyl)this is sulfonylacetanilide-2-one obtained 3-[3-(1-methyl-4-piperidyl)propyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-cyclopentyl-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-cyclopentyl-4-piperidyl)propyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-tert. -butyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-tert. -butyl-4-piperidyl)butyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-cyclopropyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-cyclopropyl-4-piperidyl)butyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-methyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-methyl-4-piperazinil)ethyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-cyclopropyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-cyclopropyl-4-piperazinil)ethyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-ethyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-ethyl-4-piperazinil)propyl]-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-isopropyl-4-piperazinil)propyl] -5-methanesulfonyl]-methyloxazolidine-2-he;

with 3-[4-(1-propyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-propyl-4-piperazinil)butyl]-5-[4-(methoxycarbonyl-methyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-it.

Similarly, by reacting methyl ester 4-piperazineethanol acid

with 3-(1-benzyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-benzyl-4-piperidyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives] -methyloxazolidine-2-he;

with 3-(1-N-BOC-amidino-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(l-N-BOC-amidino-4-piperidyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-benzyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-benzyl-4-piperidinylmethyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2 - he;

with 3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyl oxazolidin-2-he;

with 3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-benzyl-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperidyl)propyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-N-BOC-amidino-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-N-BOC-amidino-4-piperidyl)propyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-benzyl-4-piperidyl)butyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-benzyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-benzyl-4-piperazinil)ethyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-N-BOC-amidino-4-piperazinil)ethyl] -5-methanesulfonamide is oxazolidin-2-he;

with 3-[3-(1-benzyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-benzyl-4-piperazinil)propyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-benzyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-benzyl-4-piperazinil) butyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]- methyloxazolidine-2-he;

with 3-[4-(1-N-BOC-amidino-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-N-BOC-amidino-4-piperazinil)butyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-methyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-methyl-4-piperidyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives] -methyloxazolidine-2-he;

with 3-(1-isopropyl-4-piperidyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-isopropyl-4-piperidyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-(1-tert. -butyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one p is 3-(1-ethyl-4-piperidinylmethyl)-5-methanesulfonylaminoethyl-2-one obtained 3-(1-ethyl-4-piperidinylmethyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-isopropyl-4-piperidyl) ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-isopropyl-4-piperidyl)ethyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]- methyloxazolidine-2-he;

with 3-[2-(1-cyclohexyl-4-piperidyl)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-cyclohexyl-4-piperidyl)ethyl]-5-[4-(3-methoxycarbonylpropionyl)piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-methyl-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-methyl-4-piperidyl)propyl] -5-[4-(3-methoxycarbonylpropionyl)piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-cyclopentyl-4-piperidyl)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-cyclopentyl-4-piperidyl)propyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-tert. -butyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-tert.-butyl-4-piperidyl)butyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-cyclopropyl-4-piperidyl)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-cyclopropyl-4-piperidyl)butyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[2-(1-methyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-he;

with 3-[2-(1-cyclopropyl-4-piperazinil)ethyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[2-(1-cyclopropyl-4-piperazinil)ethyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-ethyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-ethyl-4-piperazinil)propyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[3-(1-isopropyl-4-piperazinil)propyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[3-(1-isopropyl-4-piperazinil)propyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-propyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-propyl-4-piperazinil)butyl]-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

with 3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-methanesulfonylaminoethyl-2-one obtained 3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-it.

EXAMPLE 4

0.6 g of 3-(1-BOC-4-piperidyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-[receive according to example 1] are suspended in 2 N. solution of hydrogen chloride in dioxane and stirred for 3 hours at room temperatire] -methyloxan-lidin-2-one-hydrochloride.

Similarly, after removal of the BOC-protective groups of the product of example 1, get:

3-(1-amidino-4-piperidyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-amidino-4-piperidinylmethyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperidyl)ethyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperazinil)propyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperazinil)butyl] -5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-it.

EXAMPLE 5

Analogously to example 4, based on the compounds of example 3, by removal of the BOC-protective groups receive the following compounds in the form of their hydrochloride:

3-(4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-amidino-4-piperidyl)-5-[4-(methoxycarbonylmethyl)-piperazine derivatives] -methoxazole the 3-[2-(1-amidino-4-piperidyl)ethyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperazinil)propyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperazinil)butyl] -5-[4-(methoxycarbonylmethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-amidino-4-piperidyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-amidino-4-piperidinylmethyl)-5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperidyl)ethyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(3- methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperazinil)propyl] -5-[4-(3-methoxycarbonylpropionyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-am) - Rev. BR>
0.8 g of 3-(1-BOC-4-piperidyl)-5-[4-(2-methoxycarbonylethyl)-piperazine derivatives]-methyloxazolidine-2-it (produced according to example 1) are suspended in 60 ml of methanol, mixed with 4 ml of 2 n NaOH solution and stirred for 4 hours at room temperature. After removal of solvent the residue is treated with water, set to pH 3 by adding diluted HCl and the reaction mixture is filtered through an ion exchanger. The filtrate is dried over magnesium sulfate. After removal of the solvent and subsequent freeze-drying receive 3-(1-BOC-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]- methyloxazolidine-2-it.

Similarly, by saponification products of examples 1 to 5 will receive:

3-(1-benzyl-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-N-BOC-amidino-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-benzyl-4-piperidinylmethyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-benzyl-4-piperidyl)ethyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-benzyl-4-piperidyl)impregnated ITIL)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-benzyl-4-piperidyl)butyl] -5-[4-(2-carboxy - ethyl)piperazine derivatives]-methyl-oxazolidin-2-he;

3-[4-(1-N-BOC-amidino-4-piperidyl)butyl]-5-[4-(2- carboxy-ethyl)piperazine derivatives]-methyl-oxazolidin-2-he;

3-[2-(1-benzyl-4-piperazinil)ethyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-N-BOC-amidino-4-piperazinil)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-benzyl-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-benzyl-4-piperazinil)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-N-BOC-amidino-4-piperazinil)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-methyl-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-isopropyl-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-tert.-butyl-4-piperidinylmethyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-ethyl-4-piperidinylmethyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-isopropyl-4-piperidyl)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-cyclohexyl-4-pipehorses)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-cyclopentyl-4-piperidyl)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-tert. -butyl-4-piperid yl)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-cyclopropyl-4-piperidyl)butyl]-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-methyl-4-piperazinil)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-cyclopropyl-4-piperazinil)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-ethyl-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-isopropyl-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-propyl-4-piperazinil)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-benzyl-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-benzyl-4-piperidinylmethyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-benzyl-4-piperidyl)ethyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-benzyl-4-piperidyl)propyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-basmati)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-benzyl-4-piperidyl)-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-N-BOC-amidino-4-piperidyl)-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-benzyl-4-piperidinylmethyl)-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-benzyl-4-piperidyl)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl]-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-benzyl-4-piperidyl)propyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-N-BOC-amidino-4-piperidyl)propyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-benzyl-4-piperidyl)butyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-benzyl-4-piperazinil)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-N-BOC-amidino-4-piperazinil)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-benzyl-4-piperazinil)propyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-N-BOC-amidino-4-piperazine kemetyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-N-BOC-amidino-4-piperazinil)butyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-methyl-4-piperidyl)-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-isopropyl-4-piperidyl)-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-tert. -butyl-4-piperidinylmethyl)-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-ethyl-4-piperidinylmethyl)-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-isopropyl-4-piperidyl)ethyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-cyclohexyl-4-piperidyl)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-methyl-4-piperidyl)propyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-cyclopentyl-4-piperidyl)propyl]-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-tert. -butyl-4-piperidyl)butyl]-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-cyclopropyl-4-piperidyl)butyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-methyl-4-piperazinil)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-cyclopropyl-4-piperazinil)ethyl]-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-ethyl-4-piperazin-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-propyl-4-piperazinil)butyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-benzyl-4-piperidyl)-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-N-BOC-amidino-4-piperidyl)-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-benzyl-4-piperidinylmethyl)-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-N-BOC-amidino-4-piperidinylmethyl)-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-benzyl-4-piperidyl)ethyl]-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-N-BOC-amidino-4-piperidyl)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-benzyl-4-piperidyl)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-N-BOC-amidino-4-piperidyl)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-benzyl-4-piperidyl)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-N-BOC-amidino-4-piperidyl)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-benzyl-4-piperazinil)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(erzini)propyl]-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-N-BOC-amidino-4-piperazinil)propyl] -5-[4-(3- carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-benzyl-4-piperazinil)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-N-BOC-amidino-4-piperazinil)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-methyl-4-piperidyl)-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-isopropyl-4-piperidyl)-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-tert. -butyl-4-piperidinylmethyl)-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-ethyl-4-piperidinylmethyl)-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-isopropyl-4-piperidyl)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-cyclohexyl-4-piperidyl)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-methyl-4-piperidyl)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-cyclopentyl-4-piperidyl)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-tert. -butyl-4-piperid yl)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-cyclopropyl-4-piperidyl)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine chlorophil-4-piperazinil)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-ethyl-4-piperazinil)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-isopropyl-4-piperazinil)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-propyl-4-piperazinil)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-cyclohexyl-4-piperazinil)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it, so pl. = 217 - 218oC;

3-(1-amidino-4-piperidyl)-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it, so pl. > 300oC;

3-(1-amidino-4-piperidinylmethyl)-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperidyl)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperidyl)butyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperazinil)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxan who yl)-5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-(1-amidino-4-piperidinylmethyl)-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperidyl)ethyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperidyl)propyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperazinil)ethyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperazinil)propyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperazinil)butyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-amidino-4-piperidyl)-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-(1-amidino-4-piperidinylmethyl)-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperidyl)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

3-[3-(1-amidino-4-Pipa�-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-it.

EXAMPLE 7

To a solution of 0.3 g of 3-(1-amidino-4-piperidyl)-5-[4-(2-carboxy ethyl)-piperazine derivatives] -methyloxazolidine-2-it in 20 ml of THF, add 10 ml of 20% NaOH solution and stirred for 24 hours at room temperature. After removal of solvent and drying vypolazhivaniem get the sodium salt of 3-(1-amidino-4-piperidyl)- 5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it.

Similarly get:

sodium salt of 3-[2-(1-amidino-4-piperidyl)ethyl] -5-[4-(2- carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it;

sodium salt of 3-[2-(1-benzyl-4-piperidyl)ethyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it;

sodium salt of 3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it;

sodium salt of 3-[3-(4-piperidyl)propyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it.

EXAMPLE 8

1.13 g 3-[2-(1-(5-Oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)ethyl]-5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-it (produced according to example 1 by reacting methyl ester 3-piperazineethanol acid 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)ethyl]-5-methanesulfonylaminoethyl-2-one and subsequent saponification of the product) is dissolved in 50 ml of methane is their vacuum. The resulting product is treated with 20 ml of ethyl acetate under heating and after cooling, the separated product is sucked off. Receive 3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it.

Similarly, by reductive removal of 5-oxo-1,2,4-oxadiazolyl group,

from 3-[3-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-get it 3-[3-(1-amidino-4-piperazinil)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[4-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)butyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[4-(1-amidino-4-piperazinil)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[2-(1-amidino-4-piperazinil)ethyl] -5- [4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[3-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)propyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine - 2-get it 3-[3-(1-amidino-4-piperazinil)propyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[4-(1-(5-oxo-1,2,4-oxo-4-piperazinil)butyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

from 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[2-(1-amidino-4-piperazinil)ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

from 3-[3-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-get it 3-[3-(1-amidino-4-piperazinil)propyl] 5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[4-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperazinil)butyl]-5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine - 2-get it 3-[4-(1-amidino-4-piperazinil)butyl]-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-it.

EXAMPLE 9

Analogously to example 8, on the basis of 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)-ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-it (produced according to example 1 by reacting methyl ester 3-(1-piperazinil)propanoic acid 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)-ethyl] -5-methanesulfonylaminoethyl-2-one and subsequent saponification of the product) by catalytic hydrogenation, to obtain 3-[2-(1-amidino-4-piperidyl)-ethyl] -5-[4-(2-carboxyethyl)-piperazine derivatives] -methyloxazolidine-2-it.

Similarly, put the)-4-piperidyl)-propyl]-5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine - 2-get it 3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[4-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)-butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(2-carboxyethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)ethyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[2-(1-amidino-4-piperidyl)ethyl]-5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[3-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)propyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine - 2-get it 3-[3-(1-amidino-4-piperidyl)propyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-he;

from 3-[4-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)butyl] -5-[4-(carboxymethyl)-piperazine derivatives] -methyloxazolidine-2-get it 3-[4-(1-amidino-4-piperidyl)butyl] -5-[4-(carboxymethyl)-piperazine derivatives]-methyloxazolidine-2-he;

from 3-[2-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)ethyl]-5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[2-(1-amidino-4-piperidyl)-ethyl] -5-[4-(3-carboxypropyl)-piperazine derivatives] -methyloxazolidine-2-he;

from 3-[3-(1-(5-oxo-1,2,4-oxadiazolyl-3-yl)-4-piperidyl)propyl] -5-[4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[3-(1-amidino-4-piperidyl)-propyl] -5-[4-(3-CT is(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-get it 3-[4-(1-amidino-4-piperidyl)butyl] -5- [4-(3-carboxypropyl)-piperazine derivatives]-methyloxazolidine-2-it.

The following examples relate to pharmaceutical compositions.

EXAMPLE: Glass vials of medicine for injection

In a solution of 100 g of biologically active substances of the formula (I) and 5 g of dinitrigenoxide in 3 l of double-distilled water was adjusted to pH 6.5 using 2 N. hydrochloric acid, the solution is sterile filtered, filled them with glass bubbles for preparations for injection, sterile conditions lyophilizer and sterile closed. Each glass bottle of medicine for injection contains 5 mg of biologically active substances.

EXAMPLE B: Candles

Melt a mixture of 20 g of biologically active substances of the formula (I) together with 100 g of soya lecithin and 1400 g of cocoa butter, poured into moulds and leave to cool. Each suppository contains 20 mg of biologically active substances.

EXAMPLE: Solution

Prepare a solution of 1 g of biologically active substances of formula I, 9.38 g of NaH2PO42H2O, 28.48 g of Na2HPO412H2O and 0.1 g of benzylaniline in 940 ml of double-distilled water. Set pH 6.8, made up to 1 l and sterilized by irradiation. This solution can be applied in the form of eye drops.

In the examples And In as biologists the example 1.

EXAMPLE D: Ointment

Mix 500 mg of biologically active substances of the formula (I) with 99.5 g of vaseline under aseptic conditions.

EXAMPLE D: Tablets

A mixture of 1 kg of biologically active substances of formula I, 4 kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate as usual pressed into tablets such that each tablet contains 10 mg of biologically active substances.

In examples G - D as a biologically active substance used, the compound of formula I with a melting point of 91 - 92oC, described in example 2.

EXAMPLE E: Bean

Analogously to example D is pressed tablets, then the usual way is applied a coating of sucrose, potato starch, talc, tragant and dye.

EXAMPLE G: Capsules

2 kg of biologically active substances of the formula (I) in the usual way bring into hard gelatin capsules so that each capsule contains 20 mg of biologically active substances.

In examples E-W as a biologically active substance used, the compound of formula I with a melting point of 217 218oC, described in example 6.

EXAMPLE C: Ampoules

A solution of 1 kg of biologically serout in sterile sterile conditions and closed. Each ampoule contains 10 mg of biologically active substances.

PHARMACOLOGICAL DATA

By analogy with the method described by Smith and al. in J. Biol. Chem. 265, 12267 - 71 (1990) and Born, C. V. R., Nature, 194, 927 - 929 (1962) defined values IC50for compounds of formula I (concentration micromole/liter, providing 50% inhibition of binding of fibrinogen to the selected receptor, i.e., inhibition of platelet aggregation) (see table).

1. Derivatives of oxazolidine formula I

< / BR>
where R1does

< / BR>
X denotes O;

Y represents substituted with R2pieperazinove the rest;

B denotes H, A, Ar-CkH2kor amending;

R2represents CrH2r- COOR3;

R3denotes H, A or benzyl;

A denotes alkyl with 1 to 6 C-atoms;

Ar denotes phenyl;

k denotes 0, 1, 2, 3 or 4;

m denotes 0;

r denotes 0, 1 or 2,

and their physiologically acceptable salts.

2. Derivatives of oxazolidine under item 1, representing

3-piperidine-4-yl-5-[4-(2-carboxyethyl)-piperazine derivatives-methyl] -oxazolidin-2-it,

3-(1-amidino-piperidine-4-yl)-5{ 4-(2-carboxyethyl)-piperazine derivatives-methyl]-oxazolidin-2-it,

3-(1-benzylpiperidine)-oxazolidin-2-it.

3. The method of obtaining compounds of formula I on p. 1, characterized in that the compound of formula II

< / BR>
where R1and X are specified in paragraph 1 values;

Z represents a reactive, esterified ester to OH-group,

enter into interaction with the compound of the formula III

H - Y,

where Y is the specified value.

4. The pharmaceutical composition active receptor antagonist adhesion, characterized in that it contains as active substance at least one compound of formula I under item 1 in an effective amount and conventional carrier or excipient.

5. Derivatives of oxazolidine formula I on PP.1 to 4 as antagonists of the adhesion receptor.

 

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The invention relates to new 4-substituted piperidine derivative that is related to ones antagonists neirokinina 2 (NK), which can be used, for example, in the treatment of diseases such as asthma, and method of production thereof

The invention relates to new derivatives of guanidine and their pharmaceutically acceptable salts, used as medicines

The invention relates to new derivatives of benzimidazole with valuable properties, in particular a derivative of benzimidazole of General formula (I)

< / BR>
where R1is methyl,

R2- benzimidazole-2-yl, unsubstituted or substituted in position 1 by the stands, imidazol-4-yl substituted in position 1 by alkyl with 1 to 3 carbon atoms, substituted in position 2 by morpholinopropan, 5,6,7,8-tetrahydro-imidazo[1,2 - a]pyridine-2-yl or propanesultone-1-Il,

R3- nonbranched alkyl with 2 to 4 carbon atoms,

R4- amino group, sulfonyl substituted by a residue from the group consisting of dimethylaminopropylamine, cycloalkylcarbonyl, benzylaminocarbonyl in which cycloalkyl part contains 5 or 6 carbon atoms and the phenyl portion may be substituted methoxy group, triptorelin, tert

The invention relates to a derivative of oxazolidinone

The invention relates to new 3-intellipedia formula I, where R1, R2, R3and R4denote H, A, OH, OA, F, Cl, Br, J, CN, CF3, COOH, CONH2, CONHA, CONA2or COOA, or R1and R2and R3and R4together denote methylenedioxy, R5Is H or OH, R6- H or R5and R6together denote a bond, And represents C1- C6-alkyl, n denotes a number from 2 to 6, and their physiologically acceptable salts

The invention relates to the field of organic chemistry, in particular to a method for producing N-aminomethyl-(meth)acrylamido General formula given in the description

The invention relates to metanarratives compounds which are antagonists of dopamine at the receptor
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