Compounds, methods for their preparation, pharmaceutical composition

 

(57) Abstract:

Described new compounds of formula 1 in which R is represented in the claims; R1denotes H, A; R2IT denotes, OA; R3represents A-CO, AG -, Het-CO, Ar-O-CO -, Ar-SO2; And denotes alkyl with 1-6 C-atoms; AG and Gets described in the claims, which have antagonistic activity against adhesion receptors and to GPIIbIIIa. Also disclosed are methods of obtaining these compounds and pharmaceutical composition thereof. The invention can be used in medicine for the preparation of drugs. 4 C. and 4 h.p. f-crystals, 1 PL.

The invention relates to novel antagonists of the adhesion receptor of the formula (1):

< / BR>
where R means

< / BR>
where = CH2WITH or CS; R10= OH or H and m =0,1,2,3 or 4;

< / BR>
where B = CH2WITH or CS; U = CH2or and R9= H, CO2H or CO2A, and n = 0,1,2 or 3;

< / BR>
with n = 1,2,3 or 4;

< / BR>
where R4= H, A-SO2Ar-SO2A-CO-or Het - CO:

< / BR>
where R5= H, And, quinil, alkenyl, each with 2-5 C atoms, or Ar;

< / BR>
where D, E, F and G each independently from each other represent CH or N, and where "k" and " l " are each independently mean amino acid residue, selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val, which is connected through a peptide bond;

< / BR>
< / BR>
where R6= H or A and m each independently of one another, denotes 0, 1, 2, 3 or 4;

< / BR>
where R7= HE, OA, OAr, Ohet, NHOH, NH2, NHA or NA2;

R8= H or A; and "n" are each, independently from each other, means 1, 2, 3 or 4; or

< / BR>
and R4has already indicated in the formula (d) value and p represents 2, 3, 4, 5 or 6;

R1denotes H, A, Ar-CO, A-CO, HE, OA or AO-CO;

R2IT denotes, OA, OAr, Ohet, NHOH, NH2, NHA or NA2;

R3represents A-CO -, Ar-CO -, Het-CO, Het-O-CO -, Ar-O-CO, A-O-CO -, Ar-SO2or A-SO2;

And denotes alkyl with 1-6 C-atoms;

Ar denotes unsubstituted or mono-, two - or three-fold substituted with A, F, Cl, Br, J, OA, -O-CH2OH, COOA, CF3, OH, NO2, CN, O-CO-A, NN2, NHA or NA2aryl with 6-10 C-atoms, diphenylmethyl or benzyl; and

Het denotes a single or dual core, saturated, unsaturated or aromatic heterocycle with 1 to 4 N, O and/or S atoms, which is unsubstituted or once may be substituted with F, Cl, Br, CF3And, HE, OA, CN or NO2; and their physiologically acceptable salts.

This problem is solved by the invention. Found that the compounds of formula (1), and their solvate and salt with good compatibility possess valuable pharmacological properties. First of all, they act as integrin inhibitors, and in particular, they inhibit the interaction of receptors3or5- integrin with a ligand. Particularly effective compounds exhibit in the case of integrins av3, av5and aIIb3. This action can be detected, for example, by the method described by J. W. Smitih, etc. in J. Biol. Chem. 265, 12267- 12271 (1990). In particular, they inhibit the binding of fibrinogen, fibronectin and von Willebrand factor with fibrinogen receptor of blood platelets (glycoprotein IIb/IIIA), as well as linking these 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-matrix. In particular, they prevent the formation trombotsitnoy of blood clots and therefore can be used for the treatment of thrombosis, apoplexy, infarcti, of ischemia, inflammation, arteriosclerosis and acute renal failure. The compounds inhibit or prevent the development of blood vessels and thus possess antiangiogenic effect. Further, the compounds have an impact on tumor cells, in that they inhibit metastasis. Thus, they can also be used as anticancer agents.

There are indications that the tumor cells due to microthrombi fall in the blood vessels and thus escaped 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 is due to the binding of fibrinogen in combination fibrinogen receptor (glycoprotein IIb/IIIA) inhibitors of the binding of fibrinogen also have value as inhibitors of metastasis. Due to its antiangiogenic abilities they prevent the blood flow and supply of nutrients to tumor cells.

Moreover, compounds suitable as antimicrobial biologically active substances, which can prevent infections caused by, for example, bacteria, fungi or yeast. Therefore, substances, the hen carry out interventions in the body, in which case apply a foreign substance, such as biomaterials, implants, catheters or electrostimulation of the heart. They act as antiseptics. Antimicrobial activity of compounds can be detected, for example, by 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-a-1 - 0 462 960. Inhibition of binding of fibrin from fibrinogen receptor can be detected by the method specified in European patent EP-A 1-0 381 033. 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 (1) and its salts, characterized in that

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

II) a compound of the formula (II):

< / BR>
where R, R1and R2have the specified values,

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

R3- X, (III)

where R3
< / BR>
where Rxmeans and R1and R3just as In are specified in paragraph 1 of the claims, values, and

Z denotes Cl, Br, J, OH or a reactive, esterified ester to OH - group,

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

< / BR>
where Y denotes-CH-(CH2)m-COR2, -N-CH(CO2R9)-(CH2)n-COR or-H-(CH2)n-COR2and U, R2, R9that "m" and "n" are specified in paragraph 1 of the claims values,

or with the compound of the formula (Vb):

< / BR>
where L represents -(CH2)n-COR2or-CH2-CH(OTHER4)-COR2and R2, R4and "n" are specified in paragraph 1 of the claims values,

X' indicates HE or produced from IT saltlike the rest;

or the compound of formula (VI):

< / BR>
where T denotes or and In, L, U and Y, and R1and R3have already specified values, enter into interaction with a reactive derivative of carbonic acid; or

(IV) to obtain the compounds of formula (1), under item 1 of the claims, with R = (e), (f), (g), (h), (i) or (k), the compound of formula (VII)

< / BR>
where R1and R3< H, with D, E, F, X, X', R6, R8and "k" have the specified values; enter into interaction with the compound of the formula (VIII);

R2- CO - Q, (VIII)

where R2has a specified value and

Q denotes

Q-CH2-CHR5-NHCO-(CH2)2-COX, -CH2CHR5-NH2.

< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
< / BR>
moreover, F, G, X, R5, R7, "k", "l", "m" and "n" have the above meanings; or

V) to obtain the compounds of formula (1), under item 1 of the claims, where R = (l), the compound of formula (IX),

< / BR>
where R1, R3, X and p have the indicated values,

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

< / BR>
where R2, R4and X' have the above meanings; or

to obtain the compounds of formula (1), under item 1 of the claims, in connection, which itself corresponds to the formula (1),

(VI) one residue R1turn in the remainder R1the fact that carry out the alkylation or acylation; or

(VII) one residue R2turn in the remainder R2that alkylate amide;

fully or partially hydrolyzing the CYANOGEN group;

atrificial to ester COOH group; or

COOH or COOA group is transferred to Albania translated into one of its salts.

The compounds of formula (1) have at least one chiral center and therefore can be in several enantiomeric forms. All of these forms (for example, R - and S - forms) and their mixtures (for example, RS - forms) are included in the formula (1).

Above and below, all residues, respectively, the parameters are specified in the case of formulas (I) - (X) values, unless nothing else. If the molecule has several equally marked groups or settings, they are, independently from each other, can take different values.

In the above formulas, the " group contains 1 to 6, preferably 1, 2, 3 or 4 C-atoms. In particular, And preferably denotes methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl or tert.-butyl; hereinafter, also pencil; 1-, 2 - or 3-methylbutyl; 1,1-, 1,2 - or 2,2 - dimethylpropyl; 1-ethyl-propyl; hexyl; 1-, 2-, 3 - or 4 - methylpentyl.

The residue is particularly preferred means:

< / BR>
with m = 0 or 1; or

< / BR>
with U = CO or CH2and n = 0, 1, or 2;

next, however, also preferably denotes;

< / BR>
< / BR>
with R4= H, A-SO2or Ar-SO2;

< / BR>
with n = 1 or 2 and R9= COOH, COOA or H;

< / BR>
with R5= H, And, quinil or alkenyl with 2-4 C-atoms or A - A;

or

< / BR>
and AS denotes amino acid residue selected from the group consisting of Ala, Arg, Asn, Asp, Cys, Gln, Glu, GLy, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr or Val, which is connected via a peptide bond.

R1represents preferably hydrogen, methyl or ethyl.

R2means preferably OH or OA, but also preferably phenyl-CH2-O-(benzyloxy group), while R3preferably refers to A -, Ar -, Het-CO, Ar-O -, Ar-SO2or A-SO2.

Ar preferably denotes phenyl, benzyl or diphenylmethyl; later, however, also preferably represents 1 - or 2-naphthyl, and these residues are preferably unsubstituted, but may also be one , two or three times substituted specified residues, in particular through A, F, Cl, Br, methylendioxy group, COOH, COOCH3O-CO-A, COOC2H5, CF3HE or OA.

Het preferably denotes 2 - or 3-furyl; 2 - or 3-thienyl; 1-, 2 - or 3-pyrrolyl; 1-, 2-, 4 - or 5 - imidazolyl; 1-, 3-, 4 - or 5-pyrazolyl; 2-, 4 - or 5-oxazolyl; 3- , 4 - or 5-isoxazolyl; 2-, 4 - or 5-thiazolyl; 3-, 4 - or 5-isothiazolin; 2-, 3 - or 4-pyridyl; 2-, 4-, 5 - or 6-pyrimidinyl; further, preferably 1,2,3-triazole-1-, -4 - or-5-yl; 1,2, 4-triazole-1- , -diazol-3 - or-5-yl; 1,2,3-thiadiazole-4 - or-5-yl; 2-, 3-, 4-, 5- or 6-2H-dipiradol; 2-, 3 - or 4-4H-dipiradol; 3 - or 4-pyridazinyl; pyrazinyl; 2-, 3-, 4-, 5-, 6- or 7-benzofuran; 2-, 3-, 4-, 5-, 6- or 7-benzothiazyl; 1-, 2-, 3-, 4-, 5-, 6- or 7 - indolyl; 1-, 2-, 4 - or 5-benzimidazolyl; 1-, 3-, 4-, 5-, 6- or 7-benzimidazolyl: 2-, 4-, 5-, 6- or 7-benzoxazolyl; 3-, 4-, 5-, 6- or 7-benzisoxazoles; 2-, 4-, 5-, 6- or 7-benzothiazolyl; 2-, 4-, 5-, 6- or 7-benzisothiazolin; 4-, 5-, 6 - or 7-benzo-2,1,3 - oxadiazole; 2-, 3-, 4-, 5-, 6-, 7- or 8-chinoline; 1-, 3-,4-, 5-, 6-, 7- or 8-ethenolysis; 1-, 2-, 3-, 4- or 9-carbazolyl; 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridine; 3-, 4-, 5-, 6-, 7- or 8-cinnoline; 2-, 4-, 5-, 6-, 7- or 8-hintline. Heterocyclic residues may also be partially or fully gidrirovanny.

Gets, therefore, may also include, for example, 2,3-dihydro-2-, -3-, -4- or-5-furyl; 2,5-dihydro-2-, -3-, -4- or-5-furyl; tetrahydro-2 - or-3-furyl; 1,3-dioxolane - 4-yl; tetrahydro-2 - or-3-thienyl; 2,3-dihydro-1-, -2-, -3-, -4- or-5-pyrrolyl; 2,5-dihydro-1-, -2-, -3-, -4- or-5-pyrrolyl; 1-, 2 - or 3-pyrrolidinyl; tetrahydro-1-, -2 - or-4-imidazolyl; 2,3-dihydro-1-, -2-, -3-, -4- or-5-pyrazolyl; tetrahydro-1-, -3 - or-4-pyrazolyl; 1,4-dihydro-1-, -2-, -3- or 4-pyridyl; 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5- or-6-pyridyl; 1,2,3,6 - tetrahydro-1-, -2-, -3-, -4-, -5- or-6-pyridyl; 1-, 2-, 3 - or 4 - piperidinyl; 2-, 3 - or 4-morphinelike-1-, -2-, -4 - or-5 - pyrimidinyl; 1-, 2 - or 3-piperazinil; 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or-8-chinoline; 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or-8-ethenolysis.

For all inventions valid is that all residues, which occur repeatedly, may be the same or different, i.e. are independent of each other.

Accordingly, the subject invention are in particular those compounds of formula (1) in which at least one of these residues has one of the abovementioned preferred meanings. Some preferred groups of compounds can be expressed by the following formulas (1a) to(1h), which correspond to the formula (1) and where more is not indicated residues are indicated in the formula (1) is, where, however,

in 1a: R stands for

< / BR>
and n = 1 or 2 and R1denotes hydrogen;

1b: R stands for

< / BR>
R10denotes hydrogen or HE; "m" = 0 or 1 and R1denotes hydrogen;

in 1c: R stands for

< / BR>
and R1denotes hydrogen;

in 1d: R, denotes

< / BR>
where l = 1 or 2; and R1denotes hydrogen;

in 1e: R stands for

< / BR>
R1denotes hydrogen and R2indicates HE or OA;

in 1f: R carts and

OR4=A-SO2-oder Ar-SO2-< / BR>
where OR4= A-SO2- or Ar - SO2;

1 g: R3= benzoyl, 1 - or 2-naphthyl, furoyl, toenail or carbobenzoxy-group and R2denotes OH or OA;

in 1h: R refers to:

< / BR>
with n = 1 or 2, U = CO or CH2; R2indicates HE or OA and R3represents benzoyl or 1 - or 2-naphthyl.

The compounds of formula (1) and also the source materials for their production, however, get itself known in ways that are described in the literature (for example in standard works, as Houben-Weil, Methods of organic chemistry, ed. Ceorq-Thieme, Stuttgart; hereinafter, J. Med. Chem. 37, 3881-3886 (1994); European patent And 1-0 381 033, European patent And 1-0 462 960), namely under reaction conditions which are known and suitable for these interactions (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 that they are not isolated from the reaction mixture, and immediately injected into the interaction further, to obtain the compounds of formula (1).

The compounds of formula (1) can be obtained by the fact that their release from their functional derivatives by Saami for solvolysis, accordingly, hydrogenolysis are those which generally correspond to the formula (1), but instead one or more free amino and/or hydroxyl groups contain corresponding protected amino and/or hydroxyl groups, preferably such that instead of the H atom, which is connected with the N - atom, contain protective for the amine function group, such that instead of HN-R groups contain N-group, where R' denotes a protective for the amine function group; and/or 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 (1), however, instead of the group - COOH contain a group-COOR", where R ' denotes a hydroxyl protective for the function group.

Also some of the same or different protected amino and/or hydroxyl groups can be present in the molecule of the original substance. If the existing protective group different from each other, they can in many cases be selectively split.

The expression "protection for the amino function group" is well known and relates to groups which are suitable for protecting (for blocking) amino group from chemical interactions, which, however, formed the groups are in particular unsubstituted or substituted acyl, aryl (e.g., 2,4-dinitrophenyl /DNF/, arelaxation (for example, benzoyloxymethyl (BPO) or kalkilya (for example, benzyl, 4-nitrobenzyl, triphenylmethyl) group. As protective for amine-function groups are removed after the desired reaction (or sequence of reactions), they were kind and magnitude, however, is not critical; however, preferably those with 1-20, in particular 1-8, C atoms.

The expression "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 (SIDE), 2-iodoxybenzoic; Uralelectromed as benzyloxycarbonyl (CBZ), 4-methoxybenzeneboronic, 9 fluorenylmethoxycarbonyl is Cecil.

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 interactions, which, however, can be easily removed after elsewhere molecules was desired chemical reaction. Typical of such groups are the abovementioned unsubstituted or substituted aryl, kalkilya or acyl group; hereinafter, also alkyl groups. The nature and magnitude protective for hydroxyl group functionality is not critical, as they again removed after the desired chemical reaction or sequence of reactions; preferred group with 1-20, in particular 1-10, 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 of formulas (II) and (III), whereby, however, at least one of the functional derivatives exercise - 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 - or p-toluensulfonate. The presence of an additional inert solvent may, but is not always necessary.

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 water. Further, taking into consideration the mixture of the above solvents.

Triperoxonane acid is preferably used in excess without the addition of another 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 0-50who tmeplate, for example, preferably using 40% triperoxonane acid in dichloromethane or using approximately 3 to 5 N. HCl in dioxane at 15-60oC; FMOC group can be split preferably by approximately 5-20% solution of dimethylamine, diethylamine or piperidine in DMF at 15-50oC. Cleavage DNP group, for example, are also carried out using approximately 3-10% solution of 2-mercaptoethanol in a mixture of DMF with water at 15-30oC.

Hydrogenations removable protective group (for example, BOM, CBZ or benzyl) can be split, 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 if this is suitable to the above, in particular, for example, alcohols, like methanol or ethanol, or amides, as DMF. Hydrogenolysis carried out usually at temperatures of about 0-100oC and pressures of about 21-200 bar, preferably operate at 20-30oC and pressures of 1-10 bar. Hydrogenolysis of CBZ - group flows well, for example, in methanol at 20-30oC in the presence of 5-10% palladium-on-charcoal grill.

The compounds of formula (I) can preferably also be obtained p is but use itself known methods for the acylation of amines.

The group X in the formula (III) preferably denotes Cl, Br, J, C1-C6-alkylsulfonate group, such as methane - or econsultancy group, or C6-C10-arylsulfonate group as benzene, p-toluene - or 1 - or 2-naphthalenesulfonate group.

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

Educt of the formula (II) are generally known and their

can be obtained, for example, according to the methods described in European patent 0 623 615 (corresponding to patent Germany 43 14 378).

To obtain amidine formula (II) to the nitrile of formula (II) to attach the ammonia. Attach carried out preferably multi-stage, however,youseo means, for example, as CH3I, translated into the corresponding complex S-alkyl-imitation, which, on its part reacts with NH3getting amidine;

b) the nitrile with an alcohol, for example ethanol, in the presence of HCl is transformed into the corresponding complex amidoethyl and it is treated with ammonia; or

C) nitrile enter into interaction with bis-(trimethylsilyl)-amidon lithium and the product is then hydrolized.

Similarly receive the corresponding N-hydroxyamides formula (II) from NITRILES, when working according to methods a) or b), but with hydroxylamine instead of ammonia. These products then you can also modify, the fact that they restore, for example, using hydrogen gas.

The compounds of formula (III) are known and most are commercially available.

The interaction of compounds of the formula (II) with compounds of the formula (III) is carried out as already described above.

Further, the compound of formula (1), where R denotes (a), (b), (c) or (d), you can get the fact that the compound of formula (IV) enter into interaction with the compound of the formula (Va) or (Vb).

The compounds of formula (IV) are partly known from European patent 0 623 615 or they can be obtained according to the described SUB>2with the compound of the formula R5CH2-CHR6-CH2OH (where R5denotes Cl, Br, or other suitable removable group, and R6OH, or R5and R6together also denote 0) to obtain the compounds of formulax-NH-CH2-CHR8-CH2OH (where R8denotes OH), interaction with a derivative of carbonic acid, as diethylcarbamyl, with 3 Rx-5-hydroxymethyl-2 - oxazolidinones and if necessary transformations hydroxymethylene group in CH2Z' - group (where Z denotes the group that you want), for example, using SOCl2, SOBr2, methanesulfonamido or p-toluensulfonate. The compounds of formula (Vb) generally known or get them by analogy with known compounds of suitable derivatives of phenol or phenol. The same counts for compounds of formula (Va). You can get them is in itself known by means of the derivatives of piperidine or piperazine.

The interaction occurs under similar conditions as described above for the reaction of compounds of formula (II) with the compound of the formula (III).

The compounds of formula (I), below, can be obtained by reacting the compounds of formula (IV) or its reaktsionnosposobnykh acid, in particular, suitable diallylmalonate as diethylcarbamyl further complicated alkalemia esters of Harborview acid, as ethylchloride. A derivative of carbonic acid, which is used in excess, preferably serves also as a solvent, respectively, a suspending means. 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. Suitable work when the reaction temperature 0-150oC, preferably in the range 70-120oC.

Educt of the formula (IV) are new. Get them, for example, by functionalization of the above compounds of formula Rx-NH-CH2-CH(OH)-CH2HE obtain compounds of the formula Rx-NH-CH2-CH(OH)-CH2-Z and interaction with compounds of the formula (Va) or (Vb).

Similarly, the compounds of formula (1), where denotes (e), (f), (g), (h), (i) or (k), you can get the fact that the compound of formula (VII) enter into interaction with the compound of the formula (VIII).

The formation of compounds of formulas (VII) and (VIII) the wasp.

For example, the compound of formula (VII) can be obtained by the fact that p-CN-aniline, which if necessary derivatization for NH2group, as already described, is transferred to p-amidaniel dinobile and then acelerou with compounds of formula R3-X, and X is preferably Cl or Br. Next, substituted with residue R3-CO-NH-C(=NR1a derivative of benzoic acid can be converted to another acid derivative or connect with the amino acid, respectively, with accordingly derivateservlet amino acid to obtain a compound of formula (VII).

Obtaining carboxylic acids, respectively, derivatives of carboxylic acids of the formula (VIII) is trivial and it can make itself known methods.

In the interaction of the compounds of formula (VII) with the compound of the formula (VIII) it is also advisable to work in the presence of base or with an excess of the basic component. As the bases are preferably usable, for example, hydroxides, carbonates, alkaline alcoholate or alkaline earth metals or organic bases like triethylamine or pyridine, which are also applied in excess and then simultaneously can serve the ol, ethanol or isopropanol, n-butanol or tert.-butanol; ethers like diethyl ether, diisopropyl ether, THF or dioxane; a simple glycol ethers as simple etilenglikolevye or monotropy ether (methylglycol or ethylglycol), simple etilenglikolevye ether (diglyme); ketones, such as acetone or butanone; NITRILES like acetonitrile; nitro compounds, as nitromethane or nitrobenzene; esters as ethyl acetate; amides, as hexamethylene phosphoric acid; sulfoxidov as dimethyl sulfoxide (DMSO); chlorinated hydrocarbons like dichloromethane, chloroform, trichloroethylene, 1,2-dichloroethane or carbon tetrachloride; hydrocarbons, as benzene, toluene or xylene. Further, suitable mixtures of these solvents with each other.

The preferred reaction temperature is the value from room temperature up to the boiling temperature of the selected solvent.

The compounds of formula (I) can also be obtained by reacting the compounds of formula (IX) with the compound of the formula (X).

On receipt of doctow formulas (IX) and (X), and the interaction of both compounds with each other, has a value already provided above for compounds of formulas (VII) and (VIII).

Further, in the ether of the formula (I) or atrificial to complex ester of carboxylic acid of the formula (I).

For the esterification to complex ester, an acid of the formula (I) (R2= H) is treated with excess alcohol of formula R2=HE (R2= A or benzyl), expediently in the presence of a strong acid like hydrochloric or sulfuric acid, at temperatures of 0-100oC, preferably 20-50oC.

On the contrary, an ester of formula (I) (R2= A or benzyl) can be transformed into the corresponding acid of formula (I) (R2= N), it is by solvolysis or hydrogenolysis 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.

Also, it is possible to completely or partially hydrolyze the cyano group.

Next, one residue R1and/or R3can be transformed into another residue R1and/or R3.

In particular, primary or secondary amino group can be alkilirovanii, allievate, amidinopropane or to provide normal protective for amine-function groups or alkyl - or arylsulfonyl groups, respectively, on the contrary, to release due to the removal of these groups.

The basis of the formula (I) with acids can be converted to the appropriate role of the accession QC 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-toluene - acid, naphthalenamine or dissolvability, louisanna acid. Salts with physiologically unacceptable acids, for example, picrate, can be used for identifying and/or purifying compounds of formula (I).

Free base of formula (I), if jelly, sodium carbonate or potassium.

You can also carboxylic acids of the formula (I) (R2= N) by introducing into engagement 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 mechanically or chemically itself by known methods. Preferably from racemic mixtures by introducing its 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. It is preferable to carry out the separation of enantiomers using filled optically active separation means (for example, as dinitrobenzoyl-phenyl-glycine) column; the solvent is suitable, for example,about, 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 compounds of formula (I) can also exist in tautomeric forms. All of these tautomers are included in the invention.

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 desired, together with one or more other biologically active substances brought to a suitable dosage forms. The thus obtained composition can be used as drugs in medicine or veterinary medicine. As carriers to apply an organic or inorganic substances which are suitable for intestinal (e.g., oral or rectal) or parenteral administration or for administration in the form pulverizing inhalation drugs and which do not react with the new compounds, for example water, vegetable oils, benzyl alcohols, polyethylene glycols, glycerol triacetate and other glycerides keys which I oral administration are, in particular 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 candles; for parenteral administration are solutions, preferably oily or aqueous solutions, furthermore, suspensions, emulsions or implants.

For use as pulverizing inhaled drugs can be used aerosols, which contain biologically active compound either dissolved or suspended in a mixture of working gases. It is reasonable to apply the biologically active agent 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 to apply, for example, for the preparation of drugs for injection. These compositions can be sterilized and/or may contain auxiliary substances, such as preservatives, stabilizers and/or wetting, emulsifying agents, salts for influencing OSMO is to contain 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, in the sale of pharmaceutical drugs, similar to the one described in European patent A-459 256 compounds, preferably in dosages of from about 5 mg to 1 g, in particular 50-500 mg, dosing unit. The daily dosage is preferably about 0.1-20 mg/kg, in particular 1-10 mg/kg 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, on 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 required, water; depending on the structure of the target product set pH value in the range of 2 to 8; filtered through a column of an ion exchanger; who eat chromatography on silica gel and/or by crystallization. In the following examples, "4-piperidinoethyl" always means "2-(4-piperidyl) ethyl"; "4-piperidinol" always means "3-(4-piperidyl) propyl and 4-piperidinoethyl" always means "4-(4-piperidyl) butyl". Similarly, "4 - piperazinylmethyl" always means "2-(4-piperazinil) ethyl"; "4 - piperazinylmethyl" always means "3-(4-piperazinil) propyl and 4-piperazinylmethyl" always means "4-(4-piperazinil) butyl". This enables also contain a protective group derived, for example, the BOC - protected compound.

Example 1

To a solution of 1.2 g of 4-ethoxycarbonylmethyl - piperazine ("And") in 20 ml DMF added 3.0 g of 3-/4-(N-benzoylamino) phenyl/-5-methanesulfonyl-oximeter-oxazolidin-2-it [produced by interaction of 4-(5-oxo-1,2,4-oxadiazolyl-3-yl) aniline with 2,3-epoxypropan-1-I to obtain N-/4-(5-oxo - 1,2,4-oxadiazolyl-3-yl) phenyl/-2,3-dihydroxy-Propylamine, interaction with diethylmalonate in the presence of tert.-the butyl potassium with 3-/4-(5-oxo-1,2,4-oxadiazolyl-3-yl) phenyl/- -5-hydroxymethyl-oxazolidin-2-it, reductive cleavage of 5-oxo-1,2,4-oxadiazolyl groups, interaction with benzoyl chloride and subsequent esterification to complex ester with methanesulfonanilide/ dissolved processing gain 3-/4-(N - benzoyl-amidino) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he; so pl. 114oC.

Similarly, by reacting "AND"

c 3-/4-(N-benzoylamino)phenyl/-5-(R)- methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N - benzoylamino)phenyl/-5-(R)-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it, so pl. 150oC;

//2D0= +33,4o(DMSO);

c 3-/4-(N-benzoylamino)phenyl/-5 (S)- methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - benzoylamino)phenyl/-5 (S) -(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it, so pl. 149oC;

//2D0= - 32.60 high.o(DMSO);

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5 - methanesulfonylaminoethyl-2-one get -/4-(N - benzyloxycarbonylamino) phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he; so pl. 129oC;

with 3-/4-(N-phenoxycarbonylamino) phenyl/-5 - methanesulfonylaminoethyl-2-one obtained 3-/4-(N - phenoxycarbonylamino) phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl) oxazolidin-2-he; so pl. 176oC;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-(3-pyridyl-carbonyl)amidino) -phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl) oxazolidin - 2-he; so pl. 134-135ooC;

with 3-/4-(N-1-naphthylamide)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-1-naphthylamide) phenyl/5- (4-ethoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he; so pl. 160-161oC;

with 3-/4-(N-2-naphthylamide)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2 - naphthylamide) phenyl/ -5-(4-ethoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-furosemidee) phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2 - furosemidee) phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he; so pl. 172-173oC;

with 3-/4-(N-3-furosemide)phenyl/-5-methansulfonate-methyl-oxazolidin - 2-one obtained 3-/4-(N-3-furosemide) phenyl/-5-(4 - ethoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-2-canolamidopropyl/-5- (4-ethoxycarbonylmethyl-piperidinomethyl)-oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-3-cyanoalanine) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonyl-amidino)-phenyl/-5 - methanesulfonylaminoethyl-2-€.sq. 186-187oC

Example 2

Analogously to example 1, by reacting 1.2 g 4 - ethoxycarbonylpyrimidine (B) in 20 ml of DMF with 3.0 g of 3-/4-(N - benzoyl-amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-[receive according to example 1], dissolved in 10 ml of DMF, after removal of the solvent and conventional treatment, receive 3-/4-(N-benzoylamino)phenyl-/5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he; so pl. 163-164oC.

Similarly, through the interaction of a "B"

with 3-/4-(N-benzoylamino)phenyl/-5(S)-methanesulfonyl-methyl - oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/- -5-(S)-(4-ethoxybenzylidene-piperidinomethyl)oxazolidin-2-it, so pl. 149-150oC.

//2D0= - 32,6 (DMSO);

with 3-/4-(N-benzoylamino)phenyl/-5-(R)-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-benzoylamino) phenyl/-5-(R)-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he; so pl. 225-226oC; //2D0=+ 33,0o(DMSO);

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-benzyloxycarbonylamino)-phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he; so pl. 130-131oC;

with 3-/4-(N-benzyloxycarbonyl(R)-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he; so pl. 133-134oC;

//2D0=+29,5o(DMSO);

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4- (N-(3-pyridylcarbonyl)amidino)phenyl/-5-methanesulfonylaminoethyl- -oxazolidin-2-one obtained 3-/4-(N-3 - pyridyl-carbonyl)amidino)-phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonyl-amidino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methoxycarbonyl-amidino)phenyl/-5-(4 - ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-it, so pl. 168oC;

with 3-/4-(N-1-methyl-piperidin-4-oxycarbonyl)amidino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-1-methylpiperidin-4-oxycarbonyl)amidino)phenyl/-5-(4 - ethoxycarbonylpyrimidine)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethylene-amidino)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)-oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one sex is naphthylamide)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one receive 3/4-(N-1-naphthylamide) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-naphthylamide) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-furosemidee) phenyl/ -5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3 - furosemide)phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-cyanoalanine)phenyl/-5- (4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-3-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3-cyanoalanine) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetamide)phenyl/-5- (4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-it.

Example 3

Analogously to example 1, on the basis of 1.2 g of 4-tert.- butoxycarbonylmethyl-piperazine ("In") in 20 ml of DMF, by introducing it in the but example 1], after removal of the solvent and conventional treatment, receive 3-/4-(N-benzoylamino)phenyl/-5-(4-tert.- butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he; so pl. 136 - 137oC.

Similarly, by interaction "IN"

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-benzyloxy - carbonamide)-phenyl/-5-(4-tert.-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it, so pl. 133oC;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-tert. -butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-(4-tert. -butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-methylpiperidin-4-oxycarbonyl)amidino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-(1-methylpiperidin-4-oxycarbonyl)amidino)phenyl/-5- (4-tert. -butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methoxycarbonyl dicarbonitrile-amidino)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-ethoxycarbonylmethylene - amidino)phenyl/-5-(4-tert.-butoxy-carbonylmethyl-piperidinomethyl)oxazolidin-2 - he; so pl. 80oC;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl/-5-(4-tert.-butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he; so pl. 205oC;

with 3-/4-(N-1-naphthylamide)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-1 - naphthylamide)phenyl/-5-(4-tert.-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he; so pl. 111-113oC;

with 3-/4-(N-2 - naphthylamide)phenyl-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4- (N-2-naphthylamide)phenyl/-5-(4-tert.- butoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl-amidino) phenyl/-5-(4-tert. -butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-it.

Example 4

Analogously to example 1, from 4-methoxycarbonylmethyl-piperazine by reacting it

with 3-/4-(N-benzyloxycarbonylamino)phenyl/ -5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-benzyloxy-carbonamide)-phenyl/-5- (4-/methoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-o(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-(3-pyridylcarbonyl) amidino)-phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin - 4-oxycarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-(1-methylpiperidin-4 - oxycarbonyl)amidino)phenyl/-5-(4-methoxycarbonylaminophenyl) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methoxycarbonylamino) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethylene-amidino)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)-oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-1-naphthylamide) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-idine) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2 - furosemidee)phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3 - furosemide)phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2 - canolamidopropyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-3 - cyanoalanine)phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - diphenylacetyl-amidino)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it.

Example 5

Analogously to example 1, from 4-isopropoxycarbonyl-piperazine, by introducing it into interaction

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N - benzyloxycarbonylamino)phenyl/-5-(4-isopropoxycarbonyl - pee the ohms get 3- /4-(N-benzoylamino)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino)phenyl/-5- (4-isopropoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-pyridylcarbonyl)amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-(3 - pyridylcarbonyl)amidino)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl)amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N- (1-methyl-piperidin - 4-oxycarbonyl)amidino) phenyl/-5-(4-isopropoxycarbonyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino) phenyl/-5-methansulfonate-methyloxazolidine get 3-/4-(N-methoxycarbonylamino)phenyl/-5- (4-isopropoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene - amidino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5- (4-isopropoxycarbonyl-piperidinomethyl)-oxazolidin-2-he

with 3-/4-(N-methylsulfonylamino)phenyl/ -5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl/-5-(4-isopropoxycarbonyl is lidin-2-one obtained 3- /4-(N-1-naphthylamide)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-2-naphthylamide)phenyl/-5- (4-isopropoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-2-furosemidee) phenyl/-5-(4-isopropoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-3 - furosemide)phenyl/-5-(4-isopropoxycarbonyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/ -5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2-cyanoalanine)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine)phenyl/ -5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3-cyanoalanine)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl- -amidino)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-it.

Example 6

Analogously to example 1, from 4-n - butoxycarbonylmethyl-piperazine, by Weeden-2-one obtained 3-/4-(N - benzyloxycarbonylamino)-phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3- /4-(N-benzoylamino)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-n-butoxycarbonylmethyl-piperidinomethyl) oxazolidin - 2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-(3 - pyridylcarbonyl)amidino)phenyl/-5-(4-n-butoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin - 4-oxycarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-(1-methylpiperidin-4 - oxycarbonyl)amidino)phenyl/-5-(4-n-butoxycarbonylmethylene) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate- -methyloxazolidine-2-one obtained 3-/4-(N - methoxycarbonylamino)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethylene-amidino)phenyl/-5-(4-n - butoxycarbonylmethyl-piperidinomethyl)-oxazo-(N-methylsulfonylamino) phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-1-naphthylamide)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methansulfonate-methyl-oxazolidin-2 - one obtained 3-/4-(N-2-naphthylamide)phenyl/-5-(4-n-butoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2-furosemidee)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3-furosemide)phenyl/-5- (4-n-butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-cyanoalanine) phenyl/-5-(4-n-butoxycarbonylmethyl-piperidinomethyl)oxazolidin - 2-he;

with 3-/4-(N-3-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3-cyanoalanine) phenyl/-5-(4-n-butoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl-amidino) phenyl/-5 - 4 - benzyloxycarbonyl-ethyl-piperazine, by introducing it into interaction

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - benzyloxycarbonylamino)-phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino) phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino)phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-3 - pyridylcarbonyl)amidino)-phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-methyl-piperidin - 4-oxycarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-(1-methylpiperidin-4 - oxycarbonyl)amidino)phenyl/-5-(4-benzyloxycarbonylamino) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methoxycarbonylamino) phenyl/-5-(4-benzyloxycarbonyloxy-methyl-oxazolidin-2-one obtained 3-/4-(N-ethoxy-carbonylmethyl-amidino) phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino) phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino)phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-N-1-naphthylamide) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin - 2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-naphthylamide) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl) oxazolidin - 2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - furosemidee)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-furosemide)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-cyanoalanine) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin - 2-he;

with 3-/4-(N-3-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3-cienojamais/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl-amidino) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl) oxazolidin-2-it.

Example 8

Analogously to example 1, from 4 - methoxycarbonylmethyl-piperazine by reacting it

with 3-/4-(N-benzyloxycarbonylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzyloxycarbonylamino)-phenyl/-5- (4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-benzoylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl-5-(4-methoxycarbonylmethyl - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-(3-pyridylcarbonyl)amidino) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl) amidino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-(1-methylpiperidin-4-oxycarbonyl)amidino) phenyl/-5-(4-methoxycarbonylaminophenyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl /-5-methansulfonate-methyloxazolidine-2-one produces ethoxycarbonylmethylene-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethylene-amidino)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)-oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl/-5-(4-methoxycarbonylmethyl-piperidinomethyl) oxazolidin-2 - he;

with 3-/4-(N-1-naphthylamide)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-1 - naphthylamide)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3- /4-(N-2-naphthylamide)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3- /4-(N-2-furosemidee)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3- /4-(N-3-furosemide)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3- /4-(N-2-cyanoalanine)phenyl/-5-(4-methoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3- /4-(N-3-cyanoalanine) phenyl/-5-(4-what phenyloxy - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-(4 - methoxycarbonylmethyl-piperazinecarboxamide-2-it.

Example 9

Analogously to example 1, from 4-isopropoxycarbonyloxymethyl by its interaction

with 3-/4-(N-benzyloxycarbonylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzyloxycarbonylamino)-phenyl/-5-(4 - isopropoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzoylamino) phenyl/-5-(4-isopropoxycarbonyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5 - methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N - phenoxycarbonylamino)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3-pyridylcarbonyl)amidino)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-methyl-piperidin-4 - oxycarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-(1-methyl-piperidin-4 - oxycarbonyl)amidino)phenyl/-5-(4 - isopropoxycarbonyloxymethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyl is) oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5-(4 - isopropoxycarbonyl-piperidinomethyl)-oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl-5-(4-isopropoxycarbonyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-1-naphthylenediamine/-5- (4-isopropoxycarbonyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - naphthylamide)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-furosemidee)phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-furosemide) phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5-methanesulfonamide)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl/ - 5/methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-3 - cyanoalanine) phenyl/-5-(4-isopropoxycarbonyl - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino) phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-(4 - isopropoxycarbonyl-piperidinomethyl)oxazolidin-2-it.

Example 10

Analogously to example 1, from 4-n - butoxycarbonylmethyl-piperazine, through its interaction

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N - benzyloxycarbonylamino)-phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl-oxazolidin-2 - one obtained 3-/4-(N-benzoylamino)phenyl/-5-(4-n - butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonyl-amidino) phenyl/-5-(4-n-butoxycarbonylmethyl-piperidinomethyl)oxazolidin - 2-he;

with 3-/4-(N-(3-pyridylcarbonyl)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-(3-pyridylcarbonyl) amidino)-phenyl/the Dino) phenyl/- -5-methane-sulfonyloxy-methyl-oxazolidin-2-one obtained 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl)amidino/phenyl/-5-(4 - n-butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/ -5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4- (N-methoxycarbonylamino)phenyl/-5- (4-n-butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylpyrimidine)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethylene-amidino/-5-/4-n - butoxycarbonyl-methyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-methylsulfonylamino)phenyl/-5- (4-n-butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-1 - naphthylamide)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-naphthylamide)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5-methansulfonate-methyl-oxazolidin-2 - one obtained 3-/4-(N-2-furosemidee)phenyl/-5-(4-n - butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5-methansulfonate-meteodyn-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - cyanoalanine)phenyl/-5-(4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3-cyanoalanine) phenyl/-5-(4-n-butoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5 - methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N - diphenylacetyl-amidino)phenyl/-5-/4-n-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it.

Example 11

Analogously to example 1, from 4 - benzyloxycarbonylamino-piperazine, through its interaction

with 3-/4-(N-benzyloxycarbonylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzyloxycarbonylamino)phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - benzoylamino)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-benzo is Livonians - methyl-oxazolidin-2-one obtained 3-/4-(N-3-pyridyl - carbonyl)amidino)-phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl)amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N- (1-methyl-piperidin-4-oxycarbonyl)amidino)phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methoxycarbonylamino) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene - amidino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-ethoxycarbonylmethyl carbarnoyl-amidino) phenyl/- 5- (4-benzyloxycarbonylamino-piperidinomethyl)-oxazolidin-2-he

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-1 - naphthylamide)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methansulfonate-methyl-oxazolidin-2 - one obtained 3-/4-(N-2-naphthylamide)phenyl/-5- (4-benzyloxycarbonylamino-piperidinomethyl)oxazolidine)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/ -5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3-furosemide)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-cyanoalanine) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine)phenyl/-5 - methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-3 - cyanoalanine)phenyl/-5-(4-benzyloxycarbonylamino - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-diphenylacetyl-amidino) phenyl/-5-(4-benzyloxycarbonylamino-piperidinomethyl)oxazolidin-2-it.

Example 12

Analogously to example 1, from 3-oxo-4 - etoxycarbonyl-ethyl-piperazine, through its interaction

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-benzyloxycarbonylamino)-phenyl/-5- (3-oxo-4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/-5- (3-oxo-4-ethoxycarbonylmethoxy-methyl-oxazolidin-2-one obtained 3-/4-(N - phenoxycarbonylamino)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-(3-pyridylcarbonyl)amidino) -phenyl/-5-(3-oxo-4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin-4 - oxycarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-(1-methyl-piperidin-4 - oxycarbonyl)amidino)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-methoxycarbonylamino) phenyl/-5-(3-oxo-4-ethoxycarbonylethyl-piperazine derivatives - methyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene - amidino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5- (3-oxo-4-ethoxycarbonylethyl-piperidinomethyl-oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino) phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-methylsulfonylamino) phenyl/-5- (3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-1-naphthylamide)phenyl/-5-(3-oxo-4-ethoxycarbonylmethyl-2-one obtained 3- /4-(N-2-naphthylamide)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-furosemidee)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-furosemide)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-cyanoalanine)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-cyanoalanine)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperazine derivatives-methyl)oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl - amidino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - diphenylacetyl-amidino)phenyl/-5-(3-oxo-4-ethoxycarbonylethyl - piperazine derivatives-methyl) oxazolidin-2-it.

Example 13

Analogously to example 1, from 3-oxo-4 - etoxycarbonyl-methyl-piperazine, through its interaction

with 3-/4-(N-benzyloxycarbonylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzyloxycarbonylamino)-phenyl/ -5-oxo-4-ethoxyl-oxazolidin-2-one obtained 3-/4-(N - benzoylamino)phenyl/-5-(3-oxo-4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he; so pl. 180-181oC;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(3-oxo-4-ethoxycarbonylmethyl-piperazine derivatives-methyl) oxazolidin-2-he;

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/- 5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N- (3-pyridylcarbonyl)amidino)-phenyl/-5-(3-oxo-4 - ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N- (1-methylpiperidin-4-oxycarbonyl-amidino)phenyl/-5-(3-oxo-4 - ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N - methoxycarbonylamino)-phenyl/-5-(3-oxo-4 - ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethylene-amidino)phenyl/-5-(3-oxo-4 - ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-methylsulfonylamino/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-1-naphthylamide)phenyl/-5-(3-oxo-4 - ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-naphthylamide)phenyl/-5- (3-oxo-4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2-furosemidee)phenyl/-5- (3-oxo-4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3-furosemide)phenyl/-5- (3-oxo-4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one get 2-/4-(N-2 - cyanoalanine)phenyl/-5-(3-oxo-4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-cyanoalanine)phenyl/-5-(3-oxo-4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - diphenylacetyl-amidino)phenyl/-5-(3-oxo-4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it.

Example 14

Analogously to example 1, from 4-etoxycarbonyl - piperidine by e the m receive 3-/4-(N-benzyloxycarbonylamino) - phenyl/-5-(4-etoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/-5- (4-etoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-phenoxycarbonylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-phenoxycarbonylamino) phenyl/-5-(4-etoxycarbonyl-piperidinomethyl)oxazolidin-2-it:

with 3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-methanesulfonylaminoethyl- -oxazolidin-2-one obtained 3-/4-(N-3 - pyridylcarbonyl)amidino)-phenyl/-5-(4-etoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-methyl-piperidin-4-oxycarbonyl)amidino)-phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4- (N-1-methyl-piperidin-4-oxycarbonyl)amidino) phenyl/-5-(4-etoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-N-methoxycarbonylamino)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-methoxycarbonylamino) phenyl/-5-(4-etoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5- (4-etoxycarbonyl-Pippin-2-one obtained 3-/4-(N-methylsulfonylamino)phenyl/-5- (4-etoxycarbonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-1 - naphthylamide)phenyl/-5-(4-etoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

4-/4-(N-2-naphthylamide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-naphthylamide)phenyl/-5-(4-etoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-furosemidee)phenyl/-5-(4-etoxycarbonyl - piperidinomethyl)oxazolidin-2-it, so pl. 158-159oC;

//2D0= + 32,70o(DMSO);

with 3-/4-(N-3-furosemide) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-furosemide)phenyl/-5-(4-etoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-cyanoalanine) phenyl)-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-2-cyanoalanine)phenyl/-5-(4-etoxycarbonyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3-cyanoalanine) phenyl/-5-(4-etoxycarbonyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-diplogin example 1, on the basis of 4 - ethoxycarbonylmethyl-4-hydroxypiperidine by its interaction

with 3-/4-(N-benzyloxycarbonylamino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - benzyloxycarbonylamino)-phenyl/-5-(4-ethoxycarbonylmethyl-4 - hydroxy-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl-oxazolidin-2 - one obtained 3-/4-(N-benzoylamino)phenyl/-5-(4 - ethoxycarbonylmethyl-4-hydroxy-piperidinomethyl)oxazolidin-2-it, so pl. 142oC;

with 3-/4-(N-phenoxycarbonylamino)phenyl-5 - methansulfonate- -methyl-oxazolidin-2-one obtained 3-/4-(N - phenoxycarbonylamino)phenyl/-5-(4-ethoxycarbonylmethyl-4 - hydroxy-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N- (3-pyridylcarbonyl)amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-pyridylcarbonyl)amidino) - phenyl/-5-(4-ethoxycarbonylmethyl-4-hydroxy-piperidinomethyl) - oxazolidin-2-he;

with 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl) amidino)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-(1-methyl-piperidin-4-oxycarbonyl)amidino) phenyl/-5-(4-etoxycarbonyl-methyl-4-hydroxy-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl/-5 - methanesulfonyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethyl-carbarnoyl-amidino)phenyl/-5-(4-ethoxycarbonylmethyl - 4-hydroxy-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methylsulfonylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-methylsulfonylamino-) phenyl/-5-(4-ethoxycarbonylmethyl-4-hydroxy-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-1-naphthylamide)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-1 - naphthylamide)phenyl/-5-(4-ethoxycarbonylmethyl-4-hydroxy - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-naphthylamide)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2-naphthylamide) phenyl/-5-(4-ethoxycarbonylmethyl-4-hydroxy-piperidino - methyl)oxazolidin-2-he;

with 3-/4-(N-2-furosemidee)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - furosemidee)phenyl/-5- (4-ethoxycarbonylmethyl-4-hydroxy - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-furosemide)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3-furosemide) phenyl/-5-(4-ethoxycarbonylmethyl-4-hydroxy-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-tacticalsniper-4-hydroxy - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-cyanoalanine) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-3-cyanoalanine)phenyl/-5-(4-ethoxy-carbonylmethyl-4 - hydroxy-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-diphenylacetyl-amidino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-diphenylacetyl-amidino) phenyl/-5-(4-ethoxycarbonylmethyl-4-hydroxy-piperidinomethyl) oxazolidin-2-it.

Example 16

0.9 g of 3-[4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl]-5-[4- -(2-etoxycarbonyl-2-N-butylsulfonyl-ethyl)phenoxymethyl-] oxazolidin-2-[receive according to example 1 by reacting 4-(5-phenyl-1,2,4-oxadiazoline-3-yl) - aniline with 2,3-epoxypropan-1-I to obtain N-/4-(5-phenyl - 1,2,4-oxadiazoline-3-yl)phenyl/-2,3-dihydroxy-Propylamine, interaction with diethylmalonate in the presence of tert.-the butyl potassium with 3-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl) phenyl/-5-hydroxymethyl-oxazolidin-2-it, esterification to complex ester with methanesulfonanilide and interaction with n- (2-etoxycarbonyl-2-N-butylsulfonyl-ethyl)-phenolate sodium] is dissolved in 50 ml of methanol and hydronaut in the presence of Raney Nickel. Then the reaction mixture is filtered and the filtrate concentrated in vacuo. Received the product about the Dino)phenyl/-5-/4-(2-etoxycarbonyl - 2-N-butylsulfonyl-ethyl/-oxazolidin-2-it.

Similarly, by reductive cleavage of 5-phenyl-1,2,4-oxadiazole groups, based on

3-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl) phenyl/-5-/4-(2-etoxycarbonyl-2-N-methylsulfonylamino - ethyl)phenoxymethyl/oxazolidin-2-get it 3-/4-(N-benzoyl - amidino)phenyl/-5-/4-(2-etoxycarbonyl-2-N-methylsulfonylamino - ethyl)phenoxymethyl/oxazolidin-2-he;

3-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-5-/4- (2-etoxycarbonyl-2- - naphthylamine-ethyl) phenoxymethyl/oxazolidin-2-get it 3-/4-(N-benzoyl-amidino) phenyl/-5-/4-(2-etoxycarbonyl- -2- -naphthylamine-ethyl)phenoxymethyl/oxazolidin-2-he;

3-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-5-/4-(2- etoxycarbonyl-2- -naphthylamine-ethyl)phenoxymethyl/oxazolidin-2 - get it 3-/4-(N-benzoyl-amidino)phenyl/-5-/4-(5-etoxycarbonyl-2- -naphthylamine-ethyl)phenoxymethyl/oxazolidin-2-it.

Example 17

0.5 g of 1-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl)-4-/4- (2-etoxycarbonyl-ethyl)piperazine derivatives/piperidine [prepared by interaction of 1-(5-phenyl-1,2,4-oxadiazoline-3-yl) -4-chloro-piperidine with 1-(2-ethoxy-carbonyl-ethyl) - piperazine] is dissolved in 50 ml of methanol and hydronaut in the presence of Raney Nickel. After that the reaction mixture is filtered and the filtrate concentrated in vacuo. Received the)phenyl/-4-/4-(2-etoxycarbonyl-ethyl) piperazine derivatives/-piperidine.

Similarly, by reductive cleavage of 5-phenyl-1,2,4-oxadiazole groups, based on

1-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-4-(1 - etoxycarbonyl-methyl-piperidine-4-yl) piperazine, get 1-/4- (N-benzoyl-amidino)phenyl/-4-(1-etoxycarbonyl-methyl-piperidine - 4-yl) piperazine;

1-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl) phenyl/-4-/4-(ethoxycarbonylmethyl)piperazine derivatives/piperidine, get 1-/4-(N - benzoyl-amidino)phenyl/-4-/4-(ethoxycarbonylmethyl) piperazine derivatives/piperidine;

1-/4-(5-phenyl-1,2,4-oxadiazoline-3 - yl)phenyl/-4-[1-(2-etoxycarbonyl-ethyl) - piperidine-4 - yl] piperazine, get 1-/4-(N-benzoyl-amidino)phenyl/-4-[1- (2-etoxycarbonyl-ethyl) - piperidine-4-yl]piperazine.

Example 18.

Analogously to example 17, from 1.1 g of 2-oxo-3-(S)- etoxycarbonyl-methyl-5-(S)-/4-(5-phenyl-1,2,4 - oxadiazoline-3-yl)-4'-oxymethylphenyl/-pyrrolidine [produced by interaction of 4-(5-phenyl-1,2,4-oxadiazoline-3-yl)-4'- hydroxy-biphenyl-sodium 2-oxo-3 (S)-etoxycarbonyl-methyl-5- (S)-methylsulphonyl-pyrrolidino] , by hydrogenation in 50 ml of methanol in the presence of Raney Nickel, after conventional treatment, get 2-oxo-3-(S)-etoxycarbonyl-methyl-5-(S)-(4-N-benzoylamino-4'- oxymethyl-biphenyl)pyrrolidin.

Similarly, poetic-5(S)-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)-4'-oxymethyl-biphenyl/pyrrolidine, get 2-oxo-3-(R)-etoxycarbonyl-methyl-5(S)-(4-N-benzoylamino 4 oxy-methyl-biphenyl) pyrrolidin;

2-oxo-3 (R)-etoxycarbonyl-methyl-5(R)-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)-4'-oxymethyl-biphenyl/pyrrolidin will receive 2-oxo-3 (R)-etoxycarbonyl-methyl-5(R)-(4-N - benzoylamino-4'-oxymethyl-biphenyl)-pyrrolidin;

2-oxo-3(S)-etoxycarbonyl-methyl-5(R)-/4-(5-phenyl-1,2,4 - Aquavision-3-yl)-4'-oxymethyl-biphenyl/pyrrolidin will receive 2-oxo-3(5)-etoxycarbonyl-methyl-5(R)-(4-N - benzoylamino-4'-oxymethyl-biphenyl/pyrrolidin.

Example 19

0.7 g of Amide N-/4-(N-benzoyl-amidino)phenyl/- succinic acid [obtained by interaction of monochlorohydrin succinic acid with n-(N-benzoyl-amidino)aniline] dissolved in 70 ml of butanol and in the presence of dicyclohexylcarbodiimide mixed with one equivalent of ethyl ester of 3-amino-4-pentenovoi acid. Then, after stirring for 3 hours at room temperature, the reaction mixture is filtered and the filtrate concentrated in vacuo. The resulting residue is treated normally. Get diamid N-/4-(N-benzoyl-amidino)-phenyl/-R'- (1-etoxycarbonyl-methyl)prop-2-in-1-yl-succinic acid.

Similarly, by reacting the amide N-/4-(N - benzoylamino)FeNi)phenyl/-N'-(1-(S)-ethoxycarbonylmethyl/-2-propyne-1-yl - succinic acid;

with ethyl ether 3 (R)-amino-4-pentenovoi acid get diamid N-/4-(N-benzoyl-amidino)phenyl/N'-(1 R) -etoxycarbonyl-methyl/-2-propyne-1-yl-succinic acid.

Example 20

Analogously to example 16, by reductive cleavage of 5-phenyl-1,2,4-oxadiazoline-group, based on 1,2,4,5 - tetrahydro-2-ethoxycarbonylmethyl-3-oxo-4-N-(2-phenylethyl)-5- /4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl-N-methylcarbamoyl/- benzodiazepine [produced by interaction 1,2,4,5-tetrahydro - 2-ethoxycarbonylmethyl-3-oxo-4-N-(2-phenylethyl)-8-carboxybenzene 4-(5-phenyl-1,2,4-oxadiazoline-3-yl)-N-methyl-aniline production], after conventional treatment, get 1,2,4,5-Tetra-hydro-2-ethoxycarbonylmethyl-3-oxo-4-N-(2-phenylethyl) -8-/4-(N-benzoylamino)phenyl-N-methylcarbamoyl/-benzodiazepin.

Example 21

0.6 g of Ethyl ester of 3-/4-(4-(N-benzoylpiperidine-4-yl)butoxy) phenyl/-3-amino-propionic acid [obtained by interaction of sodium salt of ethyl ester of 3- (4-hydroxy-phenyl)-3-N-BOC-aminopropionic acid with 1-chloro-4- (N-benzoylpiperidine-4-yl) butane and the subsequent removal of the protective group] is dissolved in 50 ml of THF, mixed with 1 equivalent of n-butyl-sulphonylchloride and stirred for two hours at room temperature. After the reaction with phenylaminopropyl acid.

Example 22

Analogously to example 16, from 1.1 g of 3-/4-(5 - phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-5-/4-(1,2- diethoxycarbonyl)piperidinomethyl/-oxazolidin-2-it [produced by interaction of 4-(5-oxo-1,2,4-oxadiazolyl-3 - yl) aniline with 2,3-epoxypropan-1-I to obtain N-/4-(5-phenyl - 1,2,4-oxadiazoline-3-yl)phenyl/ -2,3-dihydroxy-Propylamine, interaction with diethylmalonate in the presence of tert. -butyl potassium with 3-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-5-hydroxymethyl - oxazolidin-2-it, the formation of ester using methanesulfonanilide and interaction of the resulting product is 1- (1,2-diethoxycarbonyl)-piperazine], by hydrogenation him in the presence of Raney Nickel, after conventional treatment, receive 3-/4- (N-benzoylamino)phenyl/-5-/4-(1,2-di-(etoxycarbonyl)ethyl) piperidinomethyl/-oxazolidin-2-he; so pl. 136oC.

Similarly, by reductive cleavage-5-phenyl-1,2,4-oxadiazolines group.

3-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-5-/4- (1-carboxy-2-ethoxycarbonylethyl)piperidinomethyl/oxazolidin-2-get it 3-/4-(N-benzoylamino)phenyl/-5-/4-(1-carboxy-2-ethoxycarbonylethyl) - piperidinomethyl/-oxazolidin-2-he;

3-/4-(5-phenyl-1,2,4 - oxadiazoline-3-yl)Fenerbahce-1-ethoxycarbonylethyl) - piperidinomethyl/oxazolidin-2-he;

3-/4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl/-5-/4- (1,2-diethoxycarbonyl)piperidinomethyl/oxazolidin-2-get it 3-/4-(N-acetylamino)phenyl/-5-/4- (1,2-diethoxycarbonyl)piperidinomethyl/oxazolidin-2-he;

3/4-5-methyl-1,2,4-oxadiazol-3-yl) phenyl/-5-/4-(1-carboxy-2-ethoxycarbonylethyl) piperidinomethyl/oxazolidin-2-get it 3-/4-(N - acetylamino)phenyl/-5-/4-(1-carboxy-2-ethoxycarbonylethyl) - piperidinomethyl/oxazolidin-2-he;

from 3-/4-(5-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl/-5-/4- (2-carboxy-1-ethoxycarbonylethyl) piperidinomethyl/oxazolidin-2-get it 3-/4-(N - acetylamino)phenyl/-5-/4-(2-carboxy-1-ethoxycarbonylethyl) - piperidinomethyl/oxazolidin-2-he;

3-/4-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl/-5-/4- (1,2-diethoxycarbonyl)piperidinomethyl/oxazolidin-2-get it 3-/4-(N-propionamido)phenyl/-5-/4-(1,2-diethoxycarbonyl) piperidinomethyl/-oxazolidin-2-he;

3-/4-(5-ethyl-1,2,4-oxadiazol-3-yl)phenyl/-5-/4- (1-carboxy-2-ethoxycarbonylethyl)piperidinomethyl/oxazolidin-2-get it 3-/4-(N-propionamido)phenyl/-5-/4-(1-carboxy-2-ethoxycarbonylethyl) - piperidinomethyl/oxazolidin-2-he;

3-/4-(5-ethyl-1,2,4 - oxadiazol-3-yl)phenyl/-5-/4-(2-carboxy-1 - ethoxycarbonylethyl)piperidinomethyl/oxazolidin-2-he;

from 3-/4-(5-(3-pyridyl)-1,2,4-oxadiazole-3-yl)phenyl/-5-/4- (1,2-diethoxycarbonyl)piperidinomethyl/oxazolidin-2-get it 3-/4-(N-(3-pyridyl)amidino)phenyl/-5-/4-(1,2-di-ethoxycarbonylethyl) -piperidinomethyl/oxazolidin-2-he;

3-/4-(5-pyridyl)-1,2,4-oxadiazole-3-yl)phenyl/-5-/4-(1-carboxy - 2-ethoxycarbonylethyl)piperidinomethyl/oxazolidin-2-get it 3-/4-(N-(3-pyridyl)amidino)phenyl/-5-/4-(1-carboxy-2 - etoxycarbonyl-ethyl)piperazine derivatives-methyl/oxazolidin-2-he;

from 3-/4-(5-(3-pyridyl)-1,2,4-oxadiazole-3-yl)phenyl/-5-/4- (2- carboxy-1-ethoxycarbonylethyl) piperidinomethyl/oxazolidin-2-get it 3-/4-(N-(3-pyridyl) amidino)phenyl/-5-/4-(2-carboxy-1-ethoxycarbonylethyl) -piperidinomethyl/oxazolidin--2-he.

Example 23

Analogously to example 16, from 0.8 g of 1-/3- (4-hydroxy-phenyl)-2-N-(4-(5-phenyl-1,2,4-oxadiazoline-3-yl) benzoyl)aminopropionic/-4-(ethoxycarbonylmethoxy) piperidine [prepared by interaction of the acid chloride of 3-(4-hydroxyphenyl)-2-N [4-/5-phenyl-1,2,4-oxadiazoline-3-yl/benzoyl)amino-propionic acid 4-(ethoxycarbonylmethoxy)-piperidine], by hydrogenation in the presence of Raney Nickel, after conventional treatment, get 1-/3-(4-hydroxyphenyl)-2-N-(4-(N-benzoyl-amidino) benzoyl)aminopropionic/-4-(ethoxycarbonylmethoxy) - the th group,

1-/3-phenyl-2-N-(4-(5-phenyl-1,2,4-oxadiazoline-3-yl)benzoyl) -aminopropionic/-4-(ethoxycarbonylmethoxy)piperidine get 1-/3-phenyl-2-N-(4-(N-benzoyl-amidino) benzoyl/amino-propionyl/-4-(ethoxycarbonylmethoxy)piperidine;

1-/2-N-(4-(5-phenyl-1,2,4-oxadiazoline-3-yl)benzoyl) aminopropionic/-4-(ethoxycarbonylmethoxy)piperidine get 1-/2-N-(4-(N-benzoyl-amidino)benzoyl)amino-propionyl/-4- (ethoxycarbonylmethoxy)-piperidine;

1-/2-N-(4-(5-phenyl-1,2,4-oxadiazoline-3-yl)benzoyl)amino - acetyl - /-4-(ethoxycarbonylmethoxy)piperidine get 1-/2-N-(4-(N - benzoyl-amidino)benzoyl)amino-acetyl - /-4- (ethoxycarbonylmethoxy)piperidine.

Example 24

0.8 g of 3-/4-(N-Benzoyl-amidino)phenyl/-5-/4-(1,2- diethoxy-carbonylethyl)-piperidinomethyl/oxazolidin-2-[receive according to example 22] are suspended in 60 ml of methanol, mixed with 10 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 the pH-value is set to 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-/4-(N - benzoyl-amidino)phenyl/-5-/4-(1,2-dicarboxy-ethyl)pieni/-5-/4- (1,2-diethoxycarbonyl)-piperidinomethyl/oxazolidin-2-get it 3-/4-(N-acetylamino)-phenyl/-5-/4- (1,2-dicarboxy-ethyl)piperidinomethyl/-oxazolidin-2-he;

3-/4-(N-propionamido)phenyl/-5-/4- (1,2-diethoxycarbonyl)-piperidinomethyl/oxazolidin-2-get it 3-/4-(N-propionamido)-phenyl/-5-/4-(1,2- dicarboxyethyl)piperidinomethyl/oxazolidin-2-he;

3-/4-(N-(3-pyridyl)amidino)phenyl/-5-/4-(1,2-diethoxycarbonyl) piperidinomethyl-oxazolidin-2-get it 3-/4-(N- (3-pyridyl)-amidino)phenyl/-5-/4-(1,2-dicarboxyethyl)piperidinomethyl/ oxazolidin-2-it.

Example 25

Analogously to example 1, by reacting 4 - ethoxycarbonylpyrimidine ("AND")

with 3-/4-(N-4-chlorobenzylamino)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-4 - chlorobenzylamino)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-4-tormentilline)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-4-tormentilline) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-methoxybenzylidene)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-4-methoxybenzylidene)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it, so pl. 115-120oC;

with 3-/4-(N-3,4-methylenedioxyphenethylamine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3,4-R> with 3-/4-(N-4-triftoratsetilatsetonom)phenyl/ -5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-4-triftoratsetilatsetonom)phenyl/-5- (4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-lebenswelten) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3- /4-(N-4-cyanobenzylidene)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-4-methoxybenzylidene)phenyl/-5-(R)-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-4-methoxy-benzoylamino)- phenyl/-5(R)-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-it, so pl. 153-154oC;

//2D0= +31,2o(DMSO);

with 3-/4-(N-4-nitrobenzylidene)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-4-nitrobenzylidene) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-4-methylbenzylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-4-methylbenzylamino) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-4-methoxycarbonylmethylene) phenyl/-5-methane-sulfonyloxy-methyl-oxazolidin-2-one obtained 3- /4-(N-4-methoxycarbonylmethylene)phenyl/-5-(4-ethoxy - carbonyle the l - oxazolidin-2-one obtained 3-/4-(N-4-tert.-butylbenzoyl-amidino) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-3-chlorobenzylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-3-chlorobenzylamino) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-3-tormentilline)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-3-tormentilline) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-methoxybenzylidene)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3 - methoxybenzylidene) -phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3,4-dimethoxybenzamide)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3,4-dimethoxybenzamide) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-triftoratsetilatsetonom)phenyl/-5-(R)- methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - 3-triftoratsetilatsetonom)phenyl/-5(R)-(4-ethoxycarbonylmethyl - piperidinomethyl)-oxazolidin-2-he; so pl. 128-129oC;

//2D0=+29,7o(DMSO);

with 3-/4-(N-3-lebenswelten) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3-lebenswelten)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinoethyl 3-/4-(N-3-nitrobenzylidene) phenyl/-5-(4-(ethoxycarbonylmethyl-piperidinomethyl)oxazolidin - 2-he;

with 3-/4-(N-3-methylbenzylamino)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-3 - methylbenzylamino)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-3-methoxycarbonylmethylene)phenyl/-5-methane-sulfonyloxy - methyl-oxazolidin-2-one obtained 3-/4-(N-3-methoxycarbonylmethylene) phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-tert. -butylbenzylamine)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3 - tert. -butylbenzylamine)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-chlorobenzylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-chlorobenzylamino) phenyl/-5-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-tormentilline)phenyl/-5 - methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-2 - tormentilline)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-methoxybenzylidene)phenyl/ -5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2-methoxybenzylidene)phenyl/-5- (4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2,3,4-trimethoxybenzoyl-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-triftoratsetilatsetonom)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-2-triftoratsetilatsetonom)phenyl/-5-(4-ethoxycarbonylmethyl - piperazine derivatives-methyl)oxazolidin-2-he;

with 3-/4-(N-2-lebenswelten)phenyl/-5-methansulfonate-methyl-oxazolidin - 2-one obtained 3-/4-(N-2-lebenswelten)phenyl/-5- (4-ethoxycarbonylmethyl)-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-nitrobenzylidene)phenyl/ - 5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - 2-nitrobenzylidene)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-methylbenzylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-methylbenzylamino)phenyl/-5- (4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-methoxycarbonylmethylene)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - methoxycarbonylmethylene)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-tert. -butylbenzylamine)phenyl/ -5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2-tert.-butylbenzylamine)phenyl/-5- (4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-it.

Example 26


3-/4-(N-benzoylamino)phenyl/-5-(4-carboxyethyl-piperidinomethyl)- oxazolidin-2-he - diffepercent, so pl. 172oC;

3-/4-(N-benzyloxycarbonylamino)phenyl/-5-(4 - carboxyethyl-piperidinomethyl)oxazolidin-2-he-DATEFORMAT; so pl. 134oC;

3-/4-(N-phenoxycarbonylamino)phenyl/-5-(4-carboxyethyl - piperidinomethyl)oxazolidin-2-he;

3-/4-(N-(3-pyridylcarbonyl)amidino)phenyl/-5-(4-carboxyethyl - piperidinomethyl)oxazolidin-2-he;

3-/4-N-(1-methyl-piperidin-4 - oxycarbonyl)amidino)phenyl/-5-(4-carboxyethyl-piperidinomethyl) oxazolidin-2-he;

3-/4-(N-methoxycarbonylamino)phenyl/-5-(4 - carboxyethyl-piperidinomethyl)oxazolidin-2-he-DATEFORMAT-dihydrate; so pl. 99-100oC;

3-/4-(N-ethoxycarbonylmethylene-amidino)phenyl/-5- (4-carboxyethyl-piperidinomethyl)oxazolidin-2-he; so pl. 102oC;

3-/4-(N-methylsulfonylamino)phenyl/-5-(4-carboxyethyl - piperidinomethyl)oxazolidin-2-he-DATEFORMAT-hydrate; so pl. 174oC;

3-/4-(N-1-naphthylamide)phenyl/-5-(4-carboxyethyl - piperidinomethyl)-oxazolidin-2-he-DATEFORMAT; so pl. 111 - 113oC;

3-/4-(N-2-naphthylamide)phenyl/-5-(4-carboxyethyl - piperidinomethyl)-oxazolidin-2-he;

3-/4-(N-diphenylacetyl-amidino)phenyl/-5- (4-carboxyethyl-piperazine interaction 4 - ethoxycarbonylpyrimidine ("AND")

with 3-/4-(N-2-acetoxypiperidine)phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - acetoxypiperidine)-phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl) oxazolidin-2-it.

Example 28

Analogously to example 1, by reacting 4 - ethoxycarbonylethyl-piperazine

with 3-/4-(N-2-acetoxypiperidine)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-2 - acetoxypiperidine)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl) oxazolidin-2-it.

Example 29

Analogously to example 1, by reacting 4-(2 - acetoxypropionyl)-piperidine with 3-/4-(N-2 - acetoxypiperidine)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-acetoxypiperidine) phenyl/-5-/4-(2-acetoxy-phenoxycarbonyl)piperidino/oxazolidin-2-it.

Example 30

Analogously to example 1, by reacting 4-(2 - acetoxypropionyl)piperidine with 3-/4-(N - benzoylamino)phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2 - one obtained 3-/4-(N-benzoyl-amidino)phenyl/-5-(4- (2- acetoxypropionyl)piperidino/oxazolidin-2-it.

Example 31

Analogously to example 1, by reacting 4-(2 - acetoxy - phenoxycarbonylamino)piperazine with 3-/4-(N-2 - and Idina) phenyl/-5-/4-(2-acetoxypropionyl)piperidinomethyl/oxazolidin-2-it.

Example 32

Analogously to example 1, by reacting 4-(2-acetoxy - phenoxy-carbonylethyl)piperazine with 3-/4-N-2-acetoxypiperidine) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2-acetoxypiperidine)phenyl/-5-/4- (2-acetoxypropionyl)piperidinomethyl/oxazolidin-2-it.

Example 33

Analogously to example 1, by reacting 4-(2 - acetoxy-phenoxycarbonylamino)piperazine with 3-/4-(N - benzoylamino)phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2 - one obtained 3-/4-(N-benzoyl-amidino)-phenyl/-5-/4-(2- acetoxyphenyl-carbonylmethyl)piperidinomethyl/oxazolidin-2-it.

Example 34

Analogously to example 1 by reacting 4-(2 - acetoxy-phenoxycarbonylamino)piperazine with 3-/4-(N - benzoylamino)phenyl/-5-methansulfonate-methyl-oxazolidin-2 - one obtained 3-/4-(N-benzoyl-amidino)-phenyl/-5-/4-(2- acetoxyphenyl-carbonylmethyl)piperidinomethyl/oxazolidin-2-it.

Example 35

Analogously to example 1, by reacting 4 - ethoxycarbonylethyl-piperazine

with 3-/4-(N-4-chlorobenzylamino) phenyl/-5-methansulfonate-methyloxazolidine-2-one obtained 3- /4-(N-4-chlorobenzylamino)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

3/what about) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-4-methoxybenzylidene)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-4-methoxybenzylidene) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-it, so pl. 147-150oC;

with 3-/4-(N-3,4-methylenedioxyphenethylamine)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3,4 - methylenedioxyphenethylamine)phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-4-triftoratsetilatsetonom)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-4-triftoratsetilatsetonom)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he; so pl. 187oC;

with 3-/4-(N-4-lebenswelten)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-4-lebenswelten) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-4-nitrobenzylidene)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-4-nitrobenzylidene)phenyl/-5- (4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-4-methylbenzylamino)phenyl/I-methansulfonate-methyloxazolidine-2-one obtained 3-/4-(N-4 - methylbenzylamino)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

3 is xtermination) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-4-tert.-butylbenzylamine)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-4-tert.-butylbenzylamine) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-it,

with 3-/4-(N-3-chlorobenzylamino) phenyl/-5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3-chlorobenzylamino)phenyl/-5- (4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-tormentilline)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3-tormentilline)phenyl/-5- (4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-methoxybenzylidene)phenyl/-5 - methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-3 - methoxybenzylidene)-phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3,4-dimethoxybenzamide)phenyl/-5-methanesulfonylaminoethyl - oxazolidin-2-one obtained 3-/4-(N-3,4-dimethoxybenzamide) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-3-trifloromethyl-amidino)phenyl/-5-methane-sulfonyloxy - oxazolidin-2-one obtained 3-/4-(N-3-triftoratsetilatsetonom) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he; so pl. 130-131oC;

with 3-/4-(N-3-lambent oxycarbonate-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-3-nitrobenzylidene)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-3 - nitrobenzylidene)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-methylbenzylamino)phenyl/-5-methansulfonate - methyloxazolidine-2-one obtained 3-/4-(N-3-methylbenzylamino) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2 - he;:

with 3-/4-(N-3-methoxycarbonylmethylene)phenyl/-5-methansulfonate - methyl-oxazolidin-2-one obtained 3-/4-(N-3-methoxycarbonylmethylene) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-3-tert.-butylbenzylamine)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-3-tert.-butylbenzylamine) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-chlorobenzylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-chlorobenzylamino) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-he;

with 3-/4-(N-2-tormentilline)phenyl/-5- /methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - 2-tormentilline)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-methoxybenzylidene)phenyl/-5-meta piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2,3,4-trimethoxybenzylamine) phenyl/-5-methane-sulfonyloxy-methyl-oxazolidin-2-one obtained 3- /4-(N-2,3,4-trimethoxybenzylamine)phenyl/-5-(4 - ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-triftoratsetilatsetonom)phenyl/ -5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4- (N-2-triftoratsetilatsetonom)phenyl/-5- (4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-lebenswelten)phenyl/- 5-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N - 2-lebenswelten)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-nitrobenzylidene)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-2-nitrobenzylidene) phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2 - he;

with 3-/4-(N-2-methylbenzylamino)phenyl/-5-methanesulfonylaminoethyl-oxazolidin-2-one obtained 3-/4-(N-2-methylbenzylamino) -phenyl/-5-(4-ethoxycarbonylethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-methoxycarbonylmethylene)phenyl/-5 - methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-2 - methoxycarbonylmethylene)phenyl/-5-(4-ethoxycarbonylethyl - piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-2-tert.-butalbital/-5-(4-ethoxycarbonylethyl-piperidinomethyl) oxazolidin-2-it.

Example 36

Analogously to example 1, from 4-tert.- butoxycarbonyl-methyl-piperazine, through its interaction

with 3-/4-(N-benzoylamino)phenyl/-5 (R)-methansulfonate-methyl-oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/-5- (R)-methansulfonate-methyl-oxazolidin-2-it, so pl. 160oC; //D20= +32,7o;

with 3-/4-(N-benzoylamino)phenyl/-5-methansulfonate-methyl - oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/- 5-(4-tert.butoxycarbonylmethyl-piperidinomethyl)oxazolidin-2 - he; so pl. 182oC.

Example 37

Analogously to example 1, from 4-methoxycarbonylmethyl-phenolate sodium, through its interaction

with 3-/4-N-benzoylamino)phenyl/-5-chloromethyl-oxazolidin-2-one obtained 3-/4-(N-benzoylamino)phenyl/-5-(4-methoxycarbonylmethyl- -phenoxymethyl)oxazolidin-2-he; so pl. 170oC;

Analogously to example 1, from 4-(1-methoxycarbonyl-1-N - butylsulfonyl-ethyl) phenolate sodium, through its interaction with 3-/4-(N-benzoylamino)phenyl/-5-chloromethyl-oxazolidin - 2-one obtained 3-/4-(N-benzoylamino)phenyl/-5- /4-(1-methoxycarbonyl-1-N-butylsulfonyl-ethyl-phenoxymethyl) oxazolidin-2-it.

Example 38

Analogously to example 1, from 1 - ethoxy oxazolidin-2-one obtained 3-/4-(N-ethoxycarbonylmethyl)phenyl/-5 (R)-(4-etoxycarbonyl-methyl-piperidinomethyl)-2-he; so pl. 142-143oC;

with 3-/4-(N-ethoxycarbonylmethyl)phenyl/-5(S)- chloromethyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethyl)phenyl/-5(S)-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-he; so pl. 142-143oC;

with 3-/4-(N-isopropoxycarbonyl)phenyl/-5(R)-chloromethyl - oxazolidin-2-one obtained 3-/4-(N-isopropoxycarbonyl) phenyl/-5(R)-(4-ethoxycarbonylmethyl-piperidinomethyl) oxazolidin-2-he; so pl. 129-130oC, //2D0= +31,2o(DMSO);

with 3-/4-N-isopropoxycarbonyl)phenyl/-5-(S)-chloromethyl - oxazolidin-2-one obtained 3-/4-(N-isopropoxycarbonyl) phenyl/-5(S)-(4-ethoxycarbonylmethyl-piperidinomethyl)oxazolidin-2-he;

with 3-/4-(N-methoxycarbonylamino)phenyl-5(R)- chloromethyl-oxazolidin-2-one obtained 3-/4-(N - methoxycarbonylamino)phenyl/-5(R)-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it, so pl. 175-176oC.

//2D0= +51o(methanol);

with 3-/4-(N-methoxycarbonylamino) phenyl/5(S)-chloromethyl-oxazolidin-2-one obtained 3-/4-(N - methoxycarbonylamino)phenyl/-5-(S)-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it.

Similarly, on the basis of 1-tert.-butoxycarbonylmethyl-piperazine, through its interactiono
C;

with 3-/4-(N-ethoxycarbonylmethyl)phenyl/-5 - chloromethyl-oxazolidin-2-one obtained 3-/4-(N - ethoxycarbonylmethyl)phenyl/-5-(4-tert.-butoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it.

Example 39

Analogously to example 17, by reductive cleavage of 5-phenyl-1,2-4-oxadiazole group on the basis of 1-/4-(5-phenyl-1,2,4-oxadiazoline-3-yl)phenyl/-4- (4-etoxycarbonyl-piperidino)piperidine [prepared by interaction of 1-(5-phenyl-1,2,4-oxazolidin-3-yl)4-chloro-piperidine with 1-(etoxycarbonyl)piperazine under the conditions indicated in example 1], gain 1-4-N-benzoylamino)phenyl/-4-/4- (etoxycarbonyl)piperidino/piperidine; so pl. 118-119oC.

Example 40

Analogously to example 24, by saponification

/-/4-(N-benzoylamino)phenyl/-5-(4-ethoxycarbonylmethyl - piperidinomethyl)oxazolidin-2-it (so pl. 114oC, example 1) get 3-/4-(N-benzoylamino)phenyl/-5-(4-carboxymethyl-piperidinomethyl)- oxazolidin-2-he-bis-triptorelin, so pl. 91oC;

3-/4-(N-benzoylamino)phenyl/-5-(R)-(4-etoxycarbonyl - methyl-piperidinomethyl)oxazolidin-2-it (so pl. 150oC, example 1) get 3-/4-(N-benzoylamino)phenyl/-5(R)-(4-carboxymethyl - piperidinomethyl)-oxazolidin-2-he-bis-triptorelin; so pl. 147-typeparameter)oxazolidin-2-it (so pl. 181oC, example 39) get 3-/4-(N - methoxycarbonylamino)phenyl/-5-(4-carboxymethylaminomethyl) oxazolidin-2-he - bis-triptorelin; so pl. 92-93oC.

The following examples relate to pharmaceutical compositions.

Example: Glass vials of medicine for injection

A solution of 100 g of biologically active substances of the formula (1) and 5 g of dinitrigenoxide in 3 l of double-distilled water using 2 N. hydrochloric acid to establish a pH of 6.5, the solution is sterile filtered, poured into glass vials for drug injection, lyophilizer in sterile sterile conditions and closed. Each bottle of the drug 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 (1) 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 the formula (1), 9,38 g NaH2PO42 H2O, 28,48 g Na2HPO412 H2O, 0.1 g of benzylaniline in 940 ml of double-distilled water. Establish a pH of 6.8, the eh.

Example D: Ointment

Mix 500 mg of biologically active substances (1) with 99.5 g of vaseline under aseptic conditions.

Example D: Tablets

A mixture of 1 kg of biologically active substances of the formula (1), 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, so that each tablet contains 10 mg of biologically active substances.

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

Example 3: Ampoules

A solution of 1 kg of biologically active substances of the formula (1) in 60 l of double-distilled water is sterile filtered, dispensed into ampoules, lyophilizer in sterile sterile conditions and closed. Each ampoule contains 10 mg of biologically active substances.

PHARMACOLOGICAL DATA

Studies on platelet aggregation was performed in accordance with the methods of entrace collagen, necessary to induce aggregation by 20% in plasma enriched with platelets taken from the treated Guinea pigs. This limiting concentration varies from 2 μg/ml in the medium, which was treated animals, up to a maximum of 16 μg/ml to completely inhibited aggregation.

The dose of the test compounds can be increased to limit the concentration corresponding to half of its maximum value (i.e., 9 mg/ml), which is calculated as the ED1/2max and is given in the table below.

The results are shown in table 1, include the tested compounds, the values of the ED1/2max, the melting temperature and the number of examples in which these compounds are referred to, the corresponding text description of the application.

Tested compounds of the General formula:

< / BR>
Table 1 data characterize the tested compounds with values ED1/2max, proving that the referenced compounds are GPIIbIIIa antagonists.

Various diseases that are pathologically associated with increased platelet aggregation, i.e. the formation of a blood clot are a potential clinical indication for the management of GPIIbIIIa antagonists. Credity aggregation of platelets, obstructive coronary heart system or circulation of the brain.

Atherosclerotic syndrome, including the formation of atherosclerotic plaques in diseased vessels, the gap between plaques, as well as restenosis vessels after RTSA (subcutaneous transluminal coronary angioplasty), due to the high degree of adhesion of platelets and their aggregation. As shown in experiments on animals and the study of the EPIC-stage (clinical stage, phase III), GPIIbIIIa antagonists have a high potential for therapeutic impact in these clinical indications.

In addition, it is real prevention of metastasis of cancer cells GPIIbIIIa antagonists that are based on the following observations:

Circulating cancer cells can form microaggregate with platelets and in this form to stick to the walls of blood vessels. Using this mechanism facilitates the adhesion and further penetration of cancer cells in the tissue. In addition, cancer cells are covered and protected by microaggregate that prevents their recognition by cells of the immune system.

Thus, GPIIbIIIa antagonists as inhibitors of platelet aggregation should be very effective>/BR>< / BR>
where R stands for

< / BR>
where B = CH2;

R10= OH or H;

m = 0, 1,

or

< / BR>
where B = CH2U = CH2or CO;

R9= CO2H or CO2A,

n = 0, 1, 2;

< / BR>
where n = 1;

< / BR>
where R4= H, A-SO2, Ar-SO2,

< / BR>
with R5= H, A, quinil, alkenyl, each with 2 to 5 C-atoms, or Ar;

< / BR>
where D, E, F and G each, independently of one another, denotes CH or N;

k and l are each, independently of one another, denotes 0, 1 or 4, and k 0, if E and F each represents N, and l 0, if G = N;

< / BR>
where R6= H or A and m, each, independently of one another, = 0, 1;

< / BR>
and R4has already indicated in the formula (d) value;

p = 2, 3, 4,

R1denotes H, A;

R2denotes OH, OA;

R3represents A-CO -, Ar-CO -, Het-CO, Ar-O-CO -, Ar-SO2;

A denotes alkyl with 1 to 6 C-atoms;

Ar denotes unsubstituted or mono-, two - or three-fold substituted with A, F, Cl, Br, J, OA, -O-CH2-O-, COOA, COOH, O-CO-A, phenyl or 1 - or 2-naphthyl, diphenylmethyl or benzyl;

Het denotes a single or dual core, saturated or unsaturated heterocycle with 1 to 4 N, O and/or S atoms, which is not substituted or may be substituted once with F, Cl, Br, A, OH, OA,

and p. 1.

3. The compounds of formula I on p. 1 representing:

a) 3-p-(N-Benzoylamino)phenyl-5-(4-(ethoxycarbonylmethyl)-piperidinomethyl)oxazolidin-2-he;

b) 3-p-(3-pyridylcarbonyl)phenyl-5-[4-(ethoxycarbonylmethyl)-piperidinomethyl]oxazolidin-2-he;

C) 3-p-(N-methyl-4-piperidinecarbonitrile)phenyl-5-/4-(ethoxycarbonylmethyl)piperidinomethyl/oxazolidin-2-he;

d) 3-p-(N-methylsulfonylamino)phenyl-5-/4-(carboxyethylpyrrole-methyl/oxazolidin-2-he;

e) 3-p-(N-1-naphthylamide)phenyl-5-(4-carboxymethylaminomethyl)-oxazolidin-2-he;

f) 3-p-[N-(ethoxycarbonylmethylene)amidino] -phenyl-5-[4-(tert. butoxycarbonylmethyl)piperidinomethyl]oxazolidin-2-he;

g) 3-p-(N-methylsulfonylamino)phenyl-5-[-(tert. butoxycarbonyl-ethyl)piperidinomethyl]-oxazolidin-2-it.

4. The method of obtaining compounds of formula I on p. 1, characterized in that the compound of formula I release from one of its functional derivatives by treatment with solvolysis or hydrogenolysis tools.

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

< / BR>
where R, R1and R2have these values, enter into interaction with r, J, or easily displaced a group to delete.

6. Pharmaceutical composition having antagonistic activity against receptor adhesion, characterized in that it contains as active substance at least one compound of formula I under item 1 and/or one of its physiologically acceptable salt in an effective amount and at least one carrier or excipient.

7. The compounds of formula I and their physiologically acceptable salts under item 1 as receptor antagonists of adhesion.

8. The compound of formula I under item 1 and/or one of its pharmaceutically acceptable salts, which has antagonistic activity against GPIIbIIa.

 

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The invention relates to benzothiophene compounds of formula I, where R1-H, - OH, -O(C1-C4alkyl), - EA6H5-, OCO(C1-C6alkyl), or-OSO2(C2-C6alkyl);

R2IS-H, -OH, -O(C1-C4alkyl), EA6H5, CCA(C1-C6alkyl) , -OSO2(C2-C6alkyl), or halogen; R3- 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, diisopropylamino or 1 hexamethyleneimino; n = 2 or 3; Z Is-O - or-S-, or their pharmaceutically acceptable salts

The invention relates to new substituted heterocyclic compounds, process for the preparation of these compounds and pharmaceutical compositions containing them as active substances

The invention relates to the derivatives of hintline formula (I), where n = 2 and each R2independently halogen; R3- (1-4C)alkoxy; R1di-[(1-4C)alkyl]amino(2-4C)alkoxy, pyrrolidin-1-yl-(2-4C)alkoxy, piperidino-(2-4C)alkoxy, morpholino-(2-4C)alkoxy, piperazine-1-yl-(2-4C)alkoxy, 4-(1-4C)alkylpiperazine-1-yl-(2-4C)alkoxy, imidazol-1-yl-(2-4C)alkoxy, di-[(1-4C)-alkoxy-(2-4C)alkyl] amino-(2-4C)alkoxy, and any R1containing methylene group, which is not linked to the nitrogen atom or oxygen atom, and optionally contains in the indicated methylene group, a hydroxyl Deputy, or their pharmaceutically acceptable salts, processes for their preparation, pharmaceutical compositions containing these compounds, and the use of inhibitory activity of compounds to inhibit the receptor tyrosinekinase in the treatment of proliferative diseases, such as cancer

The invention relates to new derivatives of benzylpiperidine formula I, where R1denotes H or Hal, R2is unsubstituted or substituted Gal in the aromatic ring of the benzyl group in the 2 -, 3-or 4-position piperidino ring, provided that R2doesn't mean 4-benzyl when X represents-CO-, Y -, and Z represent CH2and R1- N; R3denotes H or A , X IS-CO-, Y is --CH2-, -NH - or-O-, Z is-CH2- or connection, And - alkyl WITH1-6In - OH, H+, HE, Hal Is F, Cl, Br or I, and their salts

The invention relates to new derivatives of benzimidazole and their salts formed by the addition of acids, the way they are received and microbicide tool based on them

The invention relates to new substituted heterocyclic compounds, process for the preparation of these compounds and pharmaceutical compositions containing them as active substances

The invention relates to new derivatives of oxazolidinones General formula (I) listed in the description, as well as their salt
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