4 aryloxy or 4 aaltio-piperidine derivatives, methods for their preparation, containing pharmaceutical composition and method of reception


(57) Abstract:

4 Aryloxy or 4 aaltio-piperidine derivatives of the formula I, where R1and R2each independently of one another denote a single or twofold substituted with, AND, HE, OA, phenylmethoxy, -O- (CH2)n-O-, NH2, NHAc, NAAc NHSO2A fluorine or chlorine, phenyl residues; X Is O, S or SO2; m=1; n=2; A - C1-6atoms; Ac - C1-4alkanoyl; and their physiologically acceptable salts, have an influence on the Central nervous system, preferably a damping action. 7 C. and 4 h. p. F.-ly, 1 table.

The invention relates to 4-aryloxy - or 4-aaltio-piperidinyl derivative of the formula (I):

< / BR>

R1and R2each, independently of one another, signify unsubstituted or one - or twofold substituted with A, OH, OA, aryloxy with 6-10 C atoms, aralkylated with 7-11 C atoms, -O-(CH2)n-O-, Gal, CF3, NO2, NH2, NHA, NA2, NHAc, NAAc, NHSO2A and/or NASO2A phenyl residues;

X denotes O, S, SO or SO2;

"m" denotes 1, 2 or 3;

"n" represents 1 or 2;

A stands for an alkyl residue with 1-6 C-atoms;

Gal denotes F, Cl, Br or iodine;

and Ac denotes alkanoyl with 1-8 C-atoms, arkanoid with 1-10 C-atemlosen the problem of obtaining new compounds, which can be used for the preparation of drugs.

It was found that these substances with good compatibility possess valuable pharmacological properties. For example, they have an influence on the Central nervous system, preferably the damping (e.g., soothing, trankviliziruuschem, antipsychotic and/or antidepressant) actions. In particular, the compounds have a damping effect on the behavior of mice (method see , Irwin, Psychopharmacologica, 13 (1968), 222-257). They inhibit in mice induced by apomorphine state creep (method see Costall and others, European J. Pharmacol., 50 /1968/, 39-50), or induce contralateral condition of rotation at Hemiparkison-rats (installed by the method of Ungerstedt and others, Brain Res, 24 /1970/, 485-493), without the appearance worth mentioning cataleptic side effects (method see Dolini-Stola, Pharmakopsychiat, 6, /1973/, 189-197). Further, substances inhibit the formation trithiolane agonists and antagonists of dopamine in relation to the veins receptors (set method Schwaroz etc., J. Neurochemistry, 34 /1980/, 772-778; and Creese and others, European J. Pharmacol, 46 /1977/, 377-381). Additionally, the compounds inhibit easycolocate reflex in anesthetized rats (set rukovods and blood pressure-lowering actions; so, blood pressure, measured directly from the waking, with the inserted catheter, spontaneously hypertensive rats (strain SHR /NIH-MO/ CHB-EMD method, see Weeks and Jones, Proc, Soc. Exptl. Brol. Med. 104 /1960/, 646-648), decreases after intragastric administration of the compounds.

The compound of formula (I) and their physiologically acceptable salts accession acids can therefore be used as a drug biologically active substances and also as intermediate products for the preparation of other biologically active drug substances.

The subject invention are derivatives of piperidine derivatives of the formula (I) and their salts.

The subject invention further is a method for the piperidine derivatives of formula (I) and their salts, characterized in that the compound of formula (II):

< / BR>
where R1and "m" are specified in paragraph 1 of the claims value; and

Z1denotes Z or NH2;

Z represents chlorine, bromine, iodine, OH, SO3CH3or another reactive functionally modified OH-group;

if Z1=Z, enter into interaction with the compound of the formula (III):

< / BR>
where R2and X are specified in paragraph 1 of the claims Zn is R2and X are specified in paragraph 1 of the claims value and

Z2and Z3are the same or different and, depending on the circumstances, represent chlorine, bromine, iodine, OH, SO3CH3or another reactive functionally modified OH-group;

corresponding generally to the formula (I) compound, which, however, instead of one or more hydrogen atoms contains one or more recoverable groups and/or one or more additional-SO2- and/or-SO - group, is treated with a reducing agent;

or to obtain the compounds of formula (I) under item 1 of the claims, the remainder R1and/or the remainder R2turn in the remainder R1and/or the remainder R2;

or the compound of formula (IV):

< / BR>
where R1, R2, X and m have the above values, enter into interaction with a suitable reactive derivative of carbonic acid;

or the compound of formula (V):

< / BR>
where R1and "m" have the specified values and

L denotes chlorine, bromine or other suitable removable group, enter into interaction with the compound of the formula (VI):

X1- R2,

where R2has a specified value and

X1indicates the OAU necessary, the compound of formula (I) release from one of its functional derivatives by treatment with solvolysis or hydrogenolysis means; or the compound of formula (I) by restoring or oxidation converted into another compound of formula (I); and/or the basis of the formula (I) under item 1 of the claims by treatment with acid is converted into one of its salts.

Below and above the remains of R1, R2, A, Ac, X-Gal, and the parameters "m" and "n" are listed for formula (I) values, unless nothing else.

In formulas or partial formulas "A" denotes an alkyl residue with 1-6, preferably 1,2,3 or 4 C-atoms. "A" preferably denotes methyl, next, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl or tert. -butyl; hereinafter, also pentyl, 1,2 - or 3-methyl-butyl; 1,1-, 1,2 - or 2,2-dimethyl-propyl; hexyl; 1-, 2 -, or 3-methyl-pentyl.

The remains of R1and R2may be the same or different. R1and R2preferably denote each, independently of one another, unsubstituted or substituted phenyl, and, depending on the circumstances, the substituents can be in the ortho - or meta-, particularly preferably, however, in the para-position of the phenyl residue.

In particular, R1and R2preferably represent phenyl; p-fluoro-, p-chloro, p-hydroxy, p-methoxy, p-nitro, p-methyl, p-tert.-butyl-,2also preferably represent 3,4-methylenedioxy-, p-propionamido - or p-methylsulfonyl-phenyl.

"AC" preferably denotes an acetyl or propionyl; later, however, formyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl (trimethylacetyl); further, preferably, if necessary substituted aroyl with 7-11 C atoms, and the substituents preferably take into account the following groups: alkyl, alkoxy, alkylthio, alkylsulfonyl or alkylsulfonyl, each with 1-3, preferably 1 or 2 C-atoms; methylendioxy; next, OH, fluorine, chlorine, bromine, iodine, NO2, NH2; alkylamino or dialkylamino, each with 1 to 3, preferably one or two C atoms in the alkyl group. Individual preferred rollname residues are benzoyl; o-, m - or p-toluyl; o-, m - or p-methoxy-benzoyl; 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethoxybenzoyl; 2,3,4-, 2,3,5-, 2,3,6-, 2,4,5-, 2,4,6- or 3,4,5-trimethoxybenzoyl; o-, m-, or p-methylsulfonylbenzoyl; 2,3 - or 3,4-methylenedioxybenzyl; 1 - or 2-naphtol. "AC", then, may refer to arkanoid with 1-10 C-atoms, as, for example, phenylacetyl; 2 - or 3-phenylpropionyl or 2-, 3 - or 4-phenylbutyric or 2 - or 3-phenylazophenyl.

"X" denotes preferably CI is fluorine or chlorine.

Accordingly, the subject invention are in particular those compounds of formula (I) in which at least one of these residues has one of these, in particular one of these preferred values.

Some preferred groups of compounds can be expressed by the following partial formulas (1a) to (1f), which correspond to the formula (I) and where more is not specified residues and parameters are specified for formula (I) value, where, however;

in 1a: R1denotes a p-methoxyphenyl or phenyl and

R2denotes p-acetamidophenyl;

1b: R1denotes a p-methoxyphenyl and R2denotes phenyl, m-methoxy-, p-methoxy-p-hydroxy-, p-chloro-, p-fluoro-, p-phenylmethoxy-, 3,4-methylendioxy-, p-methyl - or p-tert.-butyl-phenyl;

in 1c: R1denotes a p-methoxyphenyl; X = oxygen and m = 1;

in 1d: R2denotes p-acetamidophenyl, X = oxygen and m = 1;

in 1e: R1denotes a p-methoxyphenyl; R2denotes p-acetamido-, p-methoxy-, p-chloro-, p-methyl, p-tert.-butyl or n-methylsulfonyl-phenyl and X = sulfur;

in 1f: R1denotes a p-methoxyphenyl; R2denotes p-acetamido-, p-methoxy - or p-methylsulfonyl-phenyl and X = -SO2- . < the described in the literature (for example, in the standard works, as Houben-Weil, Methods of organic chemistry, ed. Georg-Thieme; J. March, Advanced Organic Chemistry, 3rd ed. /1985/; or Organic Reactions, both ed. John Wiley and Sons, Inc., New York), namely under reaction conditions which are known and suitable for the specified interactions. You can also use itself known here more not mentioned options.

Source materials for the proposed method in the desirable case can also be obtained in situ, so that they are not isolated from the reaction mixture, and immediately imposed on the interaction further, to obtain the compounds of formula (I).

In the compounds of formula (II) Z1means preferably Z; accordingly, the compounds of formula (II) in particular enter into interaction with derivatives of piperidine of formula (III), to obtain the compounds of formula (I). The residue Z preferably represents chlorine or bromine; however, it can also mean iodine, OH or a reactive functionally modified OH group, in particular alkylsulfonate group with 1 to 6 C-atoms (for example, methanesulfonate) or arylsulfonate group with 6 to 10 C-atoms (for example, benzosulfimide, p-toluensulfonate, 1 - or 2-naphthalenol what about the kind of connection then enter into an interaction with compounds of the formula (IIIa), in which Z2and Z3may be the same or different and preferably represent chlorine or bromine; later, however, also iodine, OH or a reactive functionally modified OH group, preferably, as above.

Compounds of formula (II), (III) and (IIIa) are partly known; the unknown compounds of the formula (II), (III) and (IIIa) can be obtained analogously to known compounds. Primary alcohols of the formula (II) are obtained, for example, by restoring the corresponding carboxylic acids or their esters. Treatment with thionyl chloride, bromoiodide, tribromide phosphorus halide or similar compounds gives the corresponding halides of the formula (II).

Sulfonyloxy-the compounds of formula (II) are obtained from the corresponding alcohols by introducing them into interaction with the corresponding anhydrides of sulfonic acids. Yodsoderzhaschie the compounds of formula (II) are obtained, for example, by exposure of potassium iodide to the corresponding ester p-toluenesulfonic acid. Amines of formula (II) are obtained, for example, from halides using phthalimide potassium or by restoring the corresponding NITRILES.

Piperidine formula (III) partly known or obtained by the analogue of the appropriate reaction or for example, by the reaction of 4-hydroxy-piperidino, and a hydroxyl group can also be functionally modified to the reactive group with the appropriate thiophenolate or thiophenolate and, if necessary, subsequent oxidation of the S-band up-SO - or-SO2-groups. The compounds of formula (IIIa) are obtained, for example, by restoring the corresponding complex diesters to diols and, if necessary, subsequent interactions with SOCl2accordingly, PBr3.

The conversion of compounds (II) and (III) proceeds by methods known from the literature for the alkylation of amines. It is possible, without the presence of solvent, the components to be fused with each other, if necessary in a sealed tube or in an autoclave. However, you can also connect to turn in the presence of an indifferent solvent. As suitable solvents, for example hydrocarbons as benzene, toluene, xylene; ketones, such as acetone, butanone; alcohols as methanol, ethanol, isopropanol, n-butanol; ethers, like tetrahydrofuran (THF) or dioxane; amides as dimethylformamide (DMF) or N-organic; NITRILES like acetonitrile, if necessary, also mixtures of these solvents with each and alkali or alkaline earth metal, carbonate or bicarbonate of alkali or alkaline earth metal or of another salt of a weak acid of the alkali or alkaline earth metal, preferably potassium, sodium or calcium, or the addition of organic bases like triethylamine, dimethylaniline, pyridine or quinoline, or an excess of amino-components, respectively, the compounds of formula (III) or (IIIa). The reaction temperature, depending on conditions, is approximately 0 - 150oC, usually 20 - 130oC.

Further, the compound of formula (I) can be obtained by the fact that forproduct that instead of hydrogen atoms contains one or more recoverable groups and/or one or more additional C-C and/or C-N-bonds is treated with a reducing agent, preferably at temperatures from -80oC to +250oC, in the presence of at least one inert solvent.

Recoverable (replaceable hydrogen groups are particularly oxygen in a carbonyl group, hydroxyl, arylsulfonate (for example, p-toluensulfonate), N-benzazolyl, N-benzyl or O-benzyl.

Fundamentally possible compounds that contain only one, or compounds that contain along with each other dorsally (I). Preferably used for this purpose catalytic hydrogenation, atomic hydrogen or certain complex metal hydrides, as NaBH4or LiAlH4.

For catalytic hydrogenation catalysts are suitable, for example, catalysts based on noble metals, Nickel and cobalt. Catalysts based on noble metals can be on the media (for example, platinum or palladium on coal; palladium on calcium carbonate or strontium carbonate), can be in the form of oxide catalysts (e.g. platinum oxide) or in the form of highly dispersed metal catalysts. Nickel and cobalt catalysts are expediently used in the form of a Raney metal, Nickel also on kieselguhr or pumice as the carrier. The hydrogenation can be performed at room temperature and normal pressure or at an elevated temperature and/or high pressure. Preferably operate at pressures of 1 to 100 atmospheres and at temperatures from -80oC to +150oC, first at a temperature of from room temperature to +100oC. Interaction, it is advisable to carry out in an acidic, neutral or alkaline region and in the presence of a solvent, such as water, metal and these solvents with each other.

If the reductant is used atomic hydrogen, it is possible to obtain, for example, by treating metals with weak acids or bases. For example, you can apply a mixture of zinc with a solution of alkali metal hydroxide or iron with acetic acid. Also suitable application of sodium or other alkali metal in alcohol, as ethanol, isopropanol, butanol, amyl or isoamyl alcohol or phenol. Further, it is possible to use Nickel-aluminum alloy in an aqueous-alkaline solution, if necessary with the addition of ethanol. To obtain atomic hydrogen suitable sodium or aluminum amalgam in aqueous-alcoholic or aqueous solution. The transformation can also be carried out in a heterogeneous phase, and appropriate use of water and benzene or toluene phase.

As reducing agents, then, you can use complex metal hydrides, as NaBH4diisobutylaluminium or NaAl(OCH2CH2OCH3)2H2and DIBORANE, if desirable, with the addition of the catalyst, as BF3, AlCl3or LiBr. As solvents for this purpose are suitable in particular ethers like diethyl ether, di-n-butyl Yu NaBH4primarily suitable alcohols as methanol or ethanol; then, water and aqueous alcohols as solvent. According to these methods, restore preferably at temperatures from -80oC to +150oC, in particular at 0 - 100oC.

The compounds of formula (I), then get that aromatic residue, R1and/or R2for example , by electrophilic substitution into another residue R1and/or R2.

The compounds of formula (I), then, is produced by the interaction of the aminoalcohols of the formula (IV) with a reactive derivative of carbonic acid. As such preferably suitable diallylmalonate as dimethyl - or diethylmalonate; esters of Harborview acid as methyl or ethyl ether of Harborview acid; N,N'-carbonyl-diimidazole or phosgene. Interaction expediently carried out in the presence of an inert solvent, preferably a halogenated hydrocarbon as chloroform; hydrocarbon like toluene, or an amide like DMF, at temperatures of about 20 to 200oC, preferably at 100 - 150oC. Derivative of carbonic acid is used in excess.

In addition, sedimentati, for example, by reacting compounds of the formula (II) (Z1= Z) with the corresponding derivatives of piperidine, enter into an interaction with compounds of the formula (VI), in conditions, which are known for the formation of ethers and simple thioethers.

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

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

rossilini groups. If the existing protective groups differ from each other, in many cases they can be selectively split.

The expression "protection for the amino group, the group is well known and relates to groups which are suitable for protecting (blocking) amino group prior to chemical interactions, which, however, can be easily removed, after passed the desired chemical reaction elsewhere in the molecule. Typical of such groups are in particular substituted or unsubstituted acyl, aryl (for example, 2,4-dinitrophenyl (DN)), arelaxation (for example, benzoyloxymethyl (BOM) or kalkilya group (for example, benzyl, 4-nitrobenzyl, triphenylmethyl). As for protective amino group after the desired reaction (or sequence of reactions) are removed, their family and size, however, is not critical; however, a preferred group with 1 to 20, especially 1 to 8 C-atoms. The expression "acyl group" in connection with the present method should be understood in its broadest sense. It covers produced from aliphatic, alifaticheskih, aromatic or heterocyclic carboxylic acids or sulfonic acids acyl group, and in particular alkoxycarbonyl, aryloxyalkyl or PR, the AK acetyl, propionyl, butyryl; arlenerina group, as phenylacetyl; aroline group as benzoyl or toluoyl; aryloxyalkanoic group, as phenoxyacetyl; alkoxycarbonyl group, as methoxycarbonyl, etoxycarbonyl, 2,2,2-trichlorocyanuric, isopropoxycarbonyl, tert.-butoxycarbonyl (BOC), 2-iodoxybenzoic; aracelikarsaalyna group, as benzyloxycarbonyl (CBZ), 4-methoxybenzeneboronic, 9-fluorenylmethoxycarbonyl (FMOC). Preferred protective for amino groups groups are BOC, DNP and BOM, then, CBZ, benzyl and acetyl.

The expression "protection for the hydroxyl group, the group is also generally known and relates to groups which are suitable for protecting a hydroxyl group against chemical interactions, which, however, can be easily removed, after passed the desired chemical reaction elsewhere in the molecule. Typical of such groups are the abovementioned unsubstituted or substituted aryl, kalkilya or acyl group; hereinafter, also alkyl groups. The nature and size of the hydroxyl protective for groups of groups is not critical, since they, after the desired chemical reaction or sequence of reactions, removed again. Preferred grouptree.-butyl, benzyl, p-nitrobenzoyl, p-toluensulfonyl and acetyl, and especially preferred benzyl and acetyl.

The release of the compounds of formula I from their functional derivatives is carried out - depending on the protective group, for example using strong acids, expediently using triperoxonane acid or perchloric acid, but also using other strong inorganic acids as hydrochloric acid or sulfuric acid, strong carboxylic acids, as trichloroacetic acid, or sulfonic acids, as benzene - or p-toluensulfonate. The presence of an additional inert solvent may, however, 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; 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, ispolzuya be reasonable about 0 - 50oC, preferably operate at 15 - 30oC (room temperature).

BOC-group can be split, 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 by about 5 to 20% solution of dimethylamine, diethylamine or piperidine in DMF at 15 - 50oC. the ratio of the DNP group is, for example, also using about 3 - 10%-aqueous solution of 2-mercaptoethanol in DMF/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, usually carried out at temperatures of 0 - 100oC and pressures of 1 to 200 bar, preferably at 20 to 30oC 1 to 10 bar. Hydrogenolysis of CBZ-group is good, for example, 5 to 10% palladium-on-coal in methanol at 20 - 30oC.

Further, the charge of the formula (I).

So, you can split ethers (O-alkyl derivatives), and form the corresponding hydroxy derivatives. For example, ethers, can be split by treatment with dimethyl sulfide complex-tribromide boron, for example, toluene, 1,2-dichloroethane, THF or dimethyl sulfoxide; by fusing with hydrohloride pyridine or aniline, preferably by pyridinecarboxamide, at about 150 - 250oC; with HBr/acetic acid or with trigliceride aluminum, in chlorinated hydrocarbons as 1,2-dichloroethane.

Compounds of General formula (I) may contain an asymmetric center. So when they are received they can be formed in the form of racemates or, if applicable optically active substances are also in optically active form. Resulting racemates, if it is desirable, in itself known methods, mechanically or chemically, can be divided into their optical antipodes. Preferably, from the racemate by entering into interaction with optically active divider formed diastereomers. Separator is suitable, for example, optical active acid, such as D - and L-forms of tartaric acid, dibenzoyltartaric acid, diatsetilvinny acid, ka is in can be divided in itself known, for example, by fractional crystallization, and optically active compounds of formula (I) is in itself known, you can release from their diastereomers.

The obtained base of formula I with acids can be converted to the corresponding salt accession acid. For this transformation is preferably suitable acid, which give physiologically acceptable salts. Thus, it is possible to use inorganic acids, such as sulfuric acid, halogen acids as hydrochloric acid or Hydrobromic acid, phosphoric acid, like phosphoric acid; nitric acid; sulfamic acid; further, organic acids, in particular aliphatic, alicyclic, analiticheskie, aromatic or heterocyclic one - or polybasic carboxylic, sulfonic or sulfuric acids, as formic acid, acetic acid, propionic acid, pavlikova acid, diethyloxalate acid, malonic acid, succinic acid, Emelyanova acid, citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinamide acid, methane - or econsultation, ethicalfashion, 2-hydroxyethanesulfonic, benzosulfimide are not physiologically acceptable (for example, the picrate), may be suitable for isolation and purification of the bases of formula (I).

Free base of formula (I), if desirable, can be free from their salts by treatment with strong bases like sodium hydroxide or potassium hydroxide, sodium carbonate or potassium.

The subject of the invention, then, is the use of compounds of formula (I) and their physiologically acceptable salts for the preparation of pharmaceutical compositions, in particular by non-chemical. While their together with at least one carrier or auxiliary substance and, if necessary, in combination with one or more other biologically active substances can be brought to a suitable dosage forms.

The subject of the invention, then, are tools, in particular pharmaceutical compositions containing at least one compound of formula (I) and/or one of its physiologically acceptable salts. These compositions can be used as a drug in human medicine and veterinary medicine. As carriers take into account organic or inorganic substances which are suitable for intestinal (e.g. oral), parenteral or topic, the polyethylene glycols, gelatin, carbohydrates as lactose or starch, magnesium stearate, talc, vaseline. For intestinal use, in particular tablets, coated tablets, capsules, syrups, juices, drops or suppositories; for parenteral administration are solutions, preferably oily or aqueous solutions, furthermore, suspensions, emulsions or implants; for topical application are ointments, creams or powders. 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 lubricants, preservatives, stabilizers and/or wetting, emulsifying agents, salts for influencing the osmotic pressure, buffer substances, dyes, improves the taste and/or aroma substances. If desirable, they can also contain one or more other biologically active substances, for example one or more vitamins.

The compounds of formula (I) and their physiologically acceptable salts can be used in therapeutic treatment of the human or animal body and in combating diseases, in particular schizophrenia and psychoreactive is high blood pressure. Further, the compounds may find application in the treatment of extrapyramidal disorders. Connections are good atypical neuroleptic drugs and their use does not cause any worthy of mention, cataleptic side effects.

This proposed according to the invention substances, usually administered by analogy with the known, commercially available drugs (Thioridazine, Haloperidol), preferably in doses of about 0.2 to 500 mg, in particular from 0.2 to 50 mg, dosing unit. The daily dose is preferably about 0.003 to 10 mg/kg body weight.

Special dose for each particular patient, however, depends on various factors, for example, the effectiveness of used special connections, age, body weight, General health, sex, cost, time of administration 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.

In the following examples, "conventional treatment" means: if necessary, water is added, extracted with dichloromethane, separated, dried body is/or by crystallization. Temperature specified in theoC. ()DValues are measured at 20oC in dimethyl sulfoxide (DMSO).

Example 1

Solution a 3.01 g of 5-(methanesulfonylaminoethyl)-3-p-methoxyphenyl - oxazolidin-2-it ("And") /is obtained by reaction of 2,3-epoxy-1-propanol with N-benzyl-p-methoxyaniline with the formation of 1-N-benzyl-p-methoxyaniline-2,3-diol, hydrogenolysis to p-methoxyaniline-propane-2,3-diol, introduction, in cooperation with diethylmalonate with the formation of 5-(hydroxymethyl)-3-p-methoxyphenyl - oxazolidin-2-she and reaction with methanesulfonamido/, 1,58 g of 4-(p-acetamidophenol)-piperidine, 1.8 g of potassium iodide and 1.4 g of potassium carbonate in 100 ml of acetonitrile is boiled for 12 hours, after cooling, is treated as usual and get 3-p-methoxyphenyl-5-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2-it.

Similarly, by reacting "A":

4-(p-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/(4-p-methoxyphenoxy-piperidino)-methyl/-oxazolidin-2-he;

4-(p-chlorophenoxy)-piperidine get 3-p-methoxyphenyl-5-/(4-p-chlorophenoxy-piperidino)-methyl/-oxazolidin-2-he;

4-(p-pertenece)-piperidine get 3-p-methoxyphenyl-5-/(4-p-pertenece-piperidino)-methyl/-oxazolidin-2 is but)-methyl/-oxazolidin-2-he (hydrochloride);

4-(p-hydroxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/(4-p-hydroxyphenoxy-piperidino)-methyl/-oxazolidin-2-he;

4-(3,4-methylenedioxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/(4-(3,4-methylenedioxyphenoxy)-piperidino)-methyl/ -oxazolidin-2-he;

4-(m-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/(4-m-methoxyphenoxy-piperidino)-methyl/-oxazolidin-2-he;

4-phenoxy-piperidine get 3-p-methoxyphenyl-5-/(4-p-phenoxy-piperidino)-methyl/-oxazolidin-2-he;

4-(p-nitrophenoxy)-piperidine get 3-p-methoxyphenyl-5-/(4-p-nitrophenoxy-piperidino)-methyl/-oxazolidin-2-he;

Example 2

Analogously to example 1, starting from 5 (R)-(methanesulfonate-methyl)-3-p-methoxyphenyl-oxazolidin-2-it, by interaction

his 4-(p-acetamidophenol)-piperidine get 3-p-methoxyphenyl-5-(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2-he (hydrochloride), so pl. 195-196oC; []D= -28,8o(DMSO).

Similarly, by reacting 5 (R)-(methane-sulfonyl-oxymethyl)-3-p-methoxyphenyl-oxazolidin-2-it

4-(p-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-methoxyphenoxy-piperidino)-methyl/-oxazolidin-2-he (hydrochloride), so pl. 249-250oC; []D= -29,9o(DMSO);

4-(p-pertenece)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-pertenece-piperidino)-methyl/-oxazolidin-2-he (hydrochloride), so pl. 246-247oC; []D= -28,9o(DMSO);

4-(p-proletarienne)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-phenylmethoxy-piperidino)-methyl/-oxazolidin-2-he (hydrochloride), so pl. 260-261oC; []D= -26,0o(DMSO);

4-(p-hydroxyphenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-hydroxyphenoxy-piperidino)-methyl/-oxazolidin-2-he (hydrochloride), so pl. 190-191oC; []D= -30,3o(DMSO);

4-(3,4-methylenedioxyphenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-(3,4-phenylmethoxy-piperidino)-methyl/ -oxazolidin-2-he (hydrochloride), so pl. 227-229oC; []D= -28,0o(DMSO);

4-(m-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-m-methoxyphenoxy-piperidino)-methyl/ -oxazolidin-2-he (hydrochloride), so pl. 208-209oC; []D= -29,1o(DMSO);

4-(p-methanesulfonylaminoethyl)-piperidine get 3-p-methoxyphenyl-5-(S)-/(4-p-methysulfonylmethane-piperidino) -methyl/-oxazolidin-2-he (hydrochloride), so pl. 184oC (decomposition); []D= -26,5o(the(hydrochloride); so pl. 227-229oC; []D= -31,6o(DMSO);

4-(p-nitrophenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-nitrophenoxy-piperidino)-methyl/-oxazolidin-2-he (hydrochloride) so pl. 250-253oC; []D= -32,7o(DMSO);

Example 3

Analogously to example 1, starting from 5(R)-(methanesulfonate-methyl)-3-p-methoxyphenyl-oxazolidin-2-it, by reacting it with 4-(p-acetamidophenyl)-piperidine get 3-p-methoxy-phenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2-he; so pl. 178-179oC; []D= -27,6o(DMSO).

Similarly, by reacting 5 (R)-(methanesulfonyl-hydroxy-methyl)-3-p-methoxyphenyl-oxazolidin-2-it

4-(p-methoxybenzylthio)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-methoxybenzylthio-piperidino)-methyl/-oxazolidin-2-he (hydrochloride) so pl. 223-225oC; []D= -31,3o(DMSO);

4-(p-chlorophenylthio)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-chlorophenylthio-piperidino)-methyl/-oxazolidin-2-he (hydrochloride) so pl. 233-236oC; []D= -30,8o(DMSO);

4-(p-methylphenylthio)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-methylphenylthio-piperidino)-methyl/-oxazolidin-2-he (hydrochloride) so pl. 226-229oC; []D= -33,6o(Dsone)-methyl/- oxazolidin-2-he (hydrochloride); so pl. 231-234oC; []D/= - 30,9o(DMSO);

4-(p-methanesulfonylaminoethyl)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-methanesulfonylaminoethyl-piperidino)-methyl/- oxazolidin-2-he; so pl. 152-154oC; []D= - 27,1o(DMSO).

Example 4

A solution of 1.2 g of 3-p-methoxyphenyl-5(S)-/(4-p-nitrophenoxy-piperidino)-methyl/-oxazolidin-one (so pl. 250-253oC; it is produced according to example 2) in 40 ml of methanol hydronaut in the presence of 0.6 g of Raney Nickel at room temperature until the cessation of hydrogen absorption /p(H2) = 1 bar/. After filtering off and after conventional treatment get 3-p-methoxyphenyl-5(S)-/(4-p-aminophenoxy-piperidino)-methyl/-oxazolidin-2-it. so pl. 236-240oC; []D- 27,2o(DMSO).

Example 5

A solution of 1.4 g of 3-p-methoxyphenyl-5(S)-/(4-p-aminophenoxy-piperidino)-methyl/-oxazolidin-2-it, and 2 ml of pyridine in 60 ml of THF is mixed dropwise with 1 ml of propionitrile and stirred for 2 hours at room temperature. After the usual processing gain 3-p-methoxy-phenyl-5(S)-/(4-p-propionylcarnitine-piperidino)-methyl/ -oxazolidin-2-it. So pl. 170-172oC; []D- 29,4o(DMSO).

Similarly, by acylation of 3-p-methoxyphenyl-5-(S)-/(is etaminophen-piperidino)-methyl/-oxazolidin-2-he (hydrochloride). So pl. 195-196oC; []D= - 28,8o(DMSO).

Example 6

A solution of 2.8 g of 3-p-methoxyphenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2-it (so pl. 195-196oC) in 40 ml of dimethylformamide under cooling with ice mixed with 0.5 g of NaH and 1.7 ml of ethyliodide and stirred for 1 hour. Then mix the following 2 hours at room temperature and, after conventional treatment, receive 3-p-methoxyphenyl-5-/(4(n-N-these-acetamido-phenoxy)-piperidino)-methyl/- oxazolidin-2-it.

Similarly, by alkylation of the secondary N-atom of the corresponding compounds of formula (I), 3-p-methoxyphenyl-5-(S)-/(4-acetamidophenol-piperidino)-methyl/-oxazolidin-2-it is using under the conditions get 3-p-methoxyphenyl-5(S)-(4-(p-N-methyl-acetamidophenol)-piperidino)-methyl/- oxazolidin-2-he (hydrochloride); so pl. 254-257oC; []D= - 28,4o(DMSO).

Example 7

Analogously to example 1, starting from 5(R)-(methanesulfonylaminoethyl)-3-phenyl-oxazolidin-2-it, by reacting it with 4-(p-acetamido-phenoxy)-piperidine get 3-phenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2-he (hydrochloride). So pl. > 260oC; []D= - 27,1o(DMSO).

Similarly, by linking ucaut 3-phenyl-5(R)-/(4-p-acetamidophenol-piperidino)-methyl/- oxazolidin-2-he (hydrochloride); so pl. > 260oC;

5(S)-(methanesulfonylaminoethyl)-3-p-chlorophenyl-oxazolidin-2-get hold 3-p-chlorophenyl-5(R)-/(4-p-acetamidophenol-piperidino)-methyl/- oxazolidin-2-he (hydrochloride); so square 264 - 266oC;

c 5(R)-(methanesulfonylaminoethyl)-3-p-chlorophenyl-oxazolidin-2-get hold 3-p-chlorophenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2 - he (hydrochloride). So pl. 264 - 266oC; []D= - 31,7o(DMSO);

c 5(S)-(methanesulfonylaminoethyl)-3-p-(phenylmethoxy)-phenyl-oxazolidin-2-get hold 3-p-(phenylmethoxy)-phenyl-5(R)-/(4-p-acetamidophenol-piperidino)-methyl/ -oxazolidin-2-he (hydrochloride); so pl. 189 - 191oC;

c 5(R)-(methanesulfonylaminoethyl)-3-p-(phenylmethoxy)-phenyl - oxazolidin-2-get hold 3-p-(phenylmethoxy)-phenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/ -oxazolidin-2-he (hydrochloride hydrate); so pl. 189 - 191oC; []D= - 22,7o(DMSO);

c 5(S)-(methanesulfonylaminoethyl)-3-p-hydroxyphenyl-oxazolidin-2-get hold 3-p-hydroxyphenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2 - he (hydrochloride); so pl. 282 - 284oC;

c 5(R)-(methanesulfonylaminoethyl)-3-p-hydroxyphenyl-oxazolidin-2-get hold 3-p-hydroxyphenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxa is)-3-p-forfinal-oxazolidin-2-get hold 3-p-forfinal-5(R)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2 - he (hydrochloride); so pl. 267 - 268oC;

c 5(R)-(methanesulfonylaminoethyl)-3-p-forfinal-oxazolidin-2-get hold 3-p-forfinal-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/-oxazolidin-2 - he (hydrochloride). So pl. 267 - 268oC; []D= - 25,5o(DMSO);

5(S)-(methanesulfonylaminoethyl)-3-p-methoxyphenyl-oxazolidin-2-get hold 3-p-methoxyphenyl-5(R)-/(4-p-acetamidophenol-piperidino)- methyl/-oxazolidin-2-he (hydrochloride). So pl. 206 - 208oC; []D= +29,9o(DMSO).

Example 8

Analogously to example 1, starting from 5-(2-methansulfonate-ethyl)-3-p-methoxyphenyl-oxazolidin-2-it, by reacting it with 4-(p-acetamidophenol)-piperidine get 3-p-methoxyphenyl-5-/2-(4-p-acetamidophenol-piperidino)-ethyl/-oxazolidin-2-he; so pl. 226-229oC.

Similarly, by reacting 5-(2-methanesulfonylaminoethyl)-3-p-methoxyphenyl-oxazolidin-2-it

4-(p-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/2-(4-p-methoxyphenoxy-piperidino)-ethyl/-oxazolidin-2-he;

4-(p-chlorophenoxy)-piperidine get 3-p-methoxyphenyl-5-/2-(4-p-chlorophenoxy-piperidino)-ethyl/-oxazolidin-2-he;

4-(p-pertenece)-piperidine get 3-p-methoxyphenyl-5-/2-(4-p-pertenece-piperidino)-ethyl/-oxazolidin-2-he; is)-ethyl/-oxazolidin-2-he;

4-(p-hydroxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/2-(4-p-hydroxyphenoxy-piperidino)-ethyl/-oxazolidin-2-he;

4-(3,4-methylenedioxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/2-(4-(3,4-methylenedioxyphenoxy)-piperidino)-ethyl/ -oxazolidin-2-he;

4-(m-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/2-(4-m-methoxyphenoxy-piperidino)-ethyl/-oxazolidin-2-he;

4-phenoxy-piperidine get 3-p-methoxyphenyl-5-/2-(4-phenoxy-piperidino)-ethyl/-oxazolidin-2-he;

4-(p-nitrophenoxy)-piperidine get 3-p-methoxyphenyl-5-/2-(4-p-nitrophenoxy-piperidino)-ethyl/-oxazolidin-2-he;

Similarly, by reacting 5-(3-methanesulfonylaminoethyl)-3-p-methoxyphenyl-oxazolidin-2-it

4-(p-acetamidophenol)-piperidine get 3-p-methoxyphenyl-5-/3-(4-p-acetamidophenol-piperidino)-propyl/-oxazolidin-2-he (dihydrochloride); so pl. 166-168oC;

4-(p-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/3-(4-p-methoxyphenoxy-piperidino)-propyl/-oxazolidin-2-he (hydrochloride);

4-(p-chlorophenoxy)-piperidine get 3-p-methoxyphenyl-5-/3-(4-p-chlorophenoxy-piperidino)-propyl/-oxazolidin-2-he;

4-(p-pertenece)-piperidine get 3-p-methoxyphenyl-5-/3-(4-p-toxigenic-5-/3-(4-p-phenylmethoxy-piperidino)-propyl/ -oxazolidin-2-he;

4-(p-hydroxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/3-(4-p-hydroxyphenoxy-piperidino)-propyl/-oxazolidin-2-he;

4-(3,4-methylenedioxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/3-(4-(3,4-methylenedioxyphenoxy)-piperidino)-propyl/ -oxazolidin-2-he;

4-(m-methoxyphenoxy)-piperidine get 3-p-methoxyphenyl-5-/3-(4-m-methoxyphenoxy-piperidino)-propyl/ -oxazolidin-2-he;

4-phenoxy-piperidine get 3-p-methoxyphenyl-5-/3-(4-phenoxy-piperidino)-propyl/ -oxazolidin-2-he;

4-(p-nitrophenoxy)-piperidine get 3-p-methoxyphenyl-5-/3-(4-p-nitrophenoxy-piperidino)-propyl/ -oxazolidin-2-he;

Example 9

Analogously to example 6, by alkylation of the secondary N - atom in the following compounds of formula (I):

3-phenyl-5-(R)-/(4-acetamidophenol-piperidino)-methyl/-oxazolidin-2-get it 3-phenyl-5-(R)-/(4-p-(N-methyl-acetamidophenol)-piperidino)-methyl/ -oxazolidin-2-he;

3-p-chlorophenyl-5(R)-/(4-p-acetamidophenol-piperidino)-methyl/- oxazolidin-2-get it 3-p-chlorophenyl-5-(R)-/(4-p-(N-methyl-acetamidophenol)-piperidino)-methyl/- oxazolidin-2-he;

3-p-chlorophenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/- oxazolidin-2-get it 3-p-chlorophenyl-5-(S)-/(4-p-(N-methyl-acetamidophenol/- oxazolidin-2-get it 3-p-(phenylmethoxy)-phenyl-5-(R)-/(4-p-(N-methyl-acetamidophenol)-piperidino) -methyl/-oxazolidin-2-he;

3-p-(phenylmethoxy)-phenyl-5(S)-/(4-p-acetamidophenol-piperidino)-methyl/- oxazolidin-2-get it 3-p-(phenylmethoxy)-phenyl-5-(S)-/(4-p-(N-methyl-acetamidophenol)-piperidino) -methyl/-oxazolidin-2-he;

3-p-hydroxyphenyl-5(R)-/(4-p-acetamidophenol-piperidino)- methyl/-oxazolidin-2-get it 3-p-methoxyphenyl-5(R)-/(4-p-(N - methyl-acetamidophenol)-piperidino)-methyl/-oxazolidin-2-he;

3-p-hydroxyphenyl-5(S)-/(4-p-acetamidophenol-piperidino)- methyl/-oxazolidin-2-get it 3-p-methoxyphenyl-5(S)-/(4-p-(N - methyl-acetamidophenol)-piperidino)-methyl/-oxazolidin-2-he;

3-p-forfinal-5(R)-/(4-p-acetamidophenol-piperidino)- methyl/-oxazolidin-2-get it 3-p-forfinal-5(R)-/(4-p-(N - methyl-acetamidophenol)-piperidino)-methyl/-oxazolidin-2-he;

3-p-forfinal-5(S)-/(4-p-acetamidophenol-piperidino)- methyl/-oxazolidin-2-get it 3-p-forfinal-5(S)-/(4-p-(N - methyl-acetamidophenol)-piperidino)-methyl/-oxazolidin-2-he;

3-p-methoxyphenyl-5(R)-/(4-p-acetamidophenol-piperidino)- methyl/-oxazolidin-2-get it 3-p-methoxyphenyl-5(R)-/(4-p-(N - methyl-acetamidophenol)-piperidino)-methyl/-oxazolidin-2-it.

Example 10

A solution of 1.2 g

3-p-methoxyphenyl-5(S)-/4-p-acetamidophenyl-dipiperidino)-methyl/ -oxazolin the Asa at 60oC. After evaporation and normal processing gain 3-p-methoxyphenyl-5(S)-/(4-p-acetamidobenzenesulfonyl-piperidino) -methyl/-oxazolidin-2-he; so pl. 174 - 176oC; []D= - 24,0o(DMSO).

Similarly, by oxidation of the corresponding dipiperidino derivatives:

3-p-methoxyphenyl-5(S)-/(4-p-methoxybenzylthio-piperidino)- methyl/-oxazolidin-2-it (hydrochloride; so pl. 223 - 225oC) get 3-p-methoxyphenyl-5(S)-/(4-p-methoxybenzenesulfonyl - piperidino)-methyl/-oxazolidin-2-he (hydrochloride); so pl. 254 - 256oC; []D=-31,6o(DMSO);

3-p-methoxyphenyl-5(S)-/(4-p-chlorophenylthio-piperidino)- methyl/-oxazolidin-2-it (hydrochloride; so pl. 233 - 236oC) get 3-p-methoxyphenyl-5(S)-/(4-p-chlorophenylsulfonyl - piperidino)-methyl/-oxazolidin-2-he;

3-p-methoxyphenyl-5(S)-/(4-p-methylphenylthio-piperidino)- methyl/-oxazolidin-2-it (hydrochloride; so pl. 226 - 229oC) get 3-p-methoxyphenyl-5(S)-/(4-p-methylanisole - piperidino)-methyl/-oxazolidin-2-he;

3-p-methoxyphenyl-5(S)-/(4-p-tert. -butylphenyl-piperidino)- methyl/-oxazolidin-2-it (hydrochloride; so pl. 231 - 234oC) get 3-p-methoxyphenyl-5(S)-/(4-p-tert. -butylphenylmethyl - piperidino)-methyl/-oxazolidin-2-he;

3-p-methoxyphenylacetyl-5(S)-/(4-p-methanesulfonylaminoethyl - piperidino)-methyl/-oxazolidin-2-he; so pl. 187 - 189oC; []D=-23,2o(DMSO).

Example 11

A solution of 1.6 g of 3-p-methoxyphenyl-5(S)= /(4-p - aminobenzamidine)methyl/-oxazolidin-2-it (produced according to example 4) and 0.9 g of methanesulfonamide (dissolved in 5 ml THF) in 100 ml THF is stirred for 3 hours at room temperature. After evaporation and normal processing gain 3-p-methoxyphenyl-5(S)-/(4 - p- -methanesulfonyl-amino-phenoxy-piperidino)-methyl/-oxazolidin-2-he (hydrochloride); so pl. 184oC (decomposition); []D=-26,5o(DMSO).

Similarly, on the basis of 3-p-methoxyphenyl-5-/2-(4 - p-aminophenoxy-piperidino)-ethyl/-oxazolidin-2-get it 3-p-methoxy-phenyl-5-/2-(4-p-methanesulfonylaminoethyl - piperidino)-ethyl/-oxazolidin-2-it.

Example 12

Analogously to example I, starting from 5(R)-(methanesulfonate-methyl)-3-p-methoxyphenyl-oxazolidin-2-it, by reacting it with 4-(3,4-Ethylenedioxy-phenoxy)-piperidine, get 3-p-methoxyphenyl-5(S)-/4(3,4-Ethylenedioxy-phenoxypyridine) -methyl/-oxazolidin-2-he (hydrochloride); so pl. 219 - 221oC; []D=-28,5o(DMSO).

Similarly, by reacting 5(R)-(methanesulfonate-methyl)-3-p-methoxyphenyl-oxazolidin-2-it;

4-(o-acetamido-fenac - 02oC []D=-22,5o(DMSO).

4-(m-acetamido-phenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-m-acetamido-phenoxy-piperidino)-methyl/- oxazolidin-2-he; So pl. 164 - 165oC []D=30.5 pero(DMSO);

4-(p-formamido-phenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-pomareda-phenoxy-piperidino)-methyl/- oxazolidin-2-he; so pl. 102 - 103oC []D=-31,2o(DMSO);

4-(p-Valeriano-phenoxy)-piperidine get 3-p-methoxyphenyl-5(S)-/(4-p-Valeriano-phenoxy-piperidino)-methyl/- 2-oxazolidinone (hydrochloride); so pl. 224 - 226oC []D= -26,7=-26,7o(DMSO);

4-(p-isobutylamino-phenoxy)-piperidine get 3-p - methoxyphenyl-5(S)-/(4-p-isobutyryl-amino-phenoxy-piperidino)- methyl)-oxazolidin-2-he (hydrochloride); so pl. 235 - 236oC; []D=-28,6o(DMSO).

Example 13

Analogously to example 1, starting from 5(R)-(methanesulfonate-methyl)-3-p-hydroxyphenyl-oxazolidin-2-it, by reacting it with 4-(p-hydroxy-phenoxy)-piperidine get 3-p-hydroxyphenyl-5(S)-/(4-p-hydroxy-phenoxy-piperidino)- methyl/-oxazolidin-2-he (hydrochloride); so pl. 241 - 245oC; []D=-28,0o(DMSO).

Similarly, by reacting 5(R)-(3 are square-p-hydroxy-phenyl-5(S)-/(4-p-propionamidoxime)- methyl/-oxazolidin-2-he; so pl. 122 - 125oC; []D=-25,0o(DMSO).

The following examples relate to pharmaceutical compositions:

Example: a Glass container with a preparation for injection

A solution of 100 g of biologically active substances of the formula (I) and 5 g of dinitrigenoxide in 3 l of double-distilled water using a 2H. hydrochloric acid set pH=6.5, the solution is sterile filtered, filled glass containers for drugs for injection, lyophilizers and sterile closed. Each glass container of medicine for injection contains 5 mg of biologically active substances.

Example B: Candles

Melt a mixture of 20 mg of biologically active substances of the formula (I) 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 (I), 9,38 g NaH2PO2H2O; 28,48 g Na2HPO412H2O and 0.1 g of benzylaniline in 940 ml of double-distilled water. Set pH 6.8, made up to 1 l and sterilized by irradiation. This solution can be applied in the form of eye drops.

Example D: Ointment

Smeserver D: Tablets

A mixture of 1 kg of biologically active substances of formula I, 4 kg of lactose, 1, 2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate as usual pressed into tablets, so that each tablet contains 10 mg of biologically active substances.

Example E: Bean

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

Example G: Capsules

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

Example C: Ampoules

A solution of 1 kg of biologically active substances of formula I in 60 l of double-distilled water is poured into ampoules under aseptic conditions lyophilizer and sterile closed. Each ampoule contains 10 mg of biologically active substances.

Pharmacological data

Inhibition, the crimps mice induced by apomorphine was determined similarly to the method described by Costello and other European J. Pharmacol., 50, 1968, 39 - 50. Determined the value of the ED50in mg/kg subcutaneous (SC) compounds of General formula I:

< / BR>
where R1and R2each independently of one another denote a single or twofold substituted with A, OH, OA, phenylmethoxy, -O-(CH2)n-O-, Hal, NH2, NHAC, NAAc and/or NHSO2A phenyl residues;

X denotes O, S or SO2;

m denotes 1;

n denotes 2;

A stands for an alkyl residue with 1 to 6 C-atoms;

Hal represents fluorine or chlorine;

Ac denotes alkanoyl with 1 to 4 C-atoms;

and their physiologically acceptable salts.

2. The enantiomer of the compounds of formula I under item 1.

3. 4 aryloxy or 4 aaltio-piperidine derivatives under item 1, representing:

(a) 3-p-chlorophenyl-5-[(4-p-acetaminophenxycodone)-methyl] -oxazolidin-2-he;

(b) 3-p-hydroxyphenyl-5-[(4-p-acetaminophenxycodone)-methyl]-oxazolidin-2-he;

(in) 3-p-methoxyphenyl-5-[(4-p-chlorphenoxamine)-methyl] -oxazolidin-2-he;

(g) 3-p-methoxyphenyl-5-[(4-p-hydroxypropylamino)-methyl]-oxazolidin-2-he;

(d) 3-p-methoxyphenyl-5-[(4-p-nitrophenoxide)-methyl] -oxazolidin-2-he;

(e) 3-p-methoxyphenyl-5-[(4-p-chlorophenylpiperazine)-methyl] -oxazolidin-2-he;

(W) 3-p-methoxyphenyl-5-[(4-p-methylvinylpyridine)-methyl] -oxazolidin-2-he;

(h) 3-p-methoxyphenyl-5 is a new derivative of the formula I on p. 1, possessing neuroleptic activity.

5. The method of obtaining 4-aryloxy or 4 aaltio-piperidinovyh derivatives of the formula I on p. 1, characterized in that the compound of formula II

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

Z1denotes Z or NH2;

Z represents chlorine, bromine, iodine, HE, SO3CH3or another reactive functionally modified HE-group if Z1denotes Z,

enter into interaction with the compound of the formula III

< / BR>
where R2and X are specified in paragraph 1 values

or, if Z1denotes NH2enter into interaction with the compound of the formula IIIa

< / BR>
where R2and X are specified in paragraph 1 values

Z2and Z3are the same or different and each represents chlorine, bromine, iodine, HE, SO3CH3or another reactive functionally modified IT group.

6. The method of obtaining 4-aryloxy or 4 aaltio-piperidinovyh derivatives of the formula I on p. 1, characterized in that connection, usually corresponding to the formula I, which instead of one or more hydrogen atoms contains one or more recoverable groups and/or one or more of the si - or 4-aaltio-piperidinovyh derivatives of the formula I on p. 1, characterized in that for obtaining the compounds of formula I, the residue R1and/or R2turn in the remainder R1and/or R2.

8. The method of obtaining 4-aryloxy - or 4-aaltio-piperidinovyh derivatives of the formula I on p. 1, characterized in that the compound of formula I on p. 1 release from one of its functional derivatives by treatment with solvolysis or hydrogenolysis funds, or the compound of formula I by recovery or oxidation converted into another compound of formula I.

9. The method according to PP.5 to 8, characterized in that the base of the formula I on p. 1 by treatment with acid is converted into one of its salts.

10. Pharmaceutical composition having neuroleptic activity, characterized in that it contains at least one compound of formula I under item 1 and/or one of its physiologically acceptable salts and pharmaceutically acceptable excipients or carriers.

11. A method of obtaining a pharmaceutical composition, characterized in that the compound of formula I under item 1 and/or one of its physiologically acceptable salts together with at least one solid, liquid or semi-liquid carrier or auxiliary


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The invention relates to medicine, namely to the chemical-pharmaceutical industry and relates to pharmaceutical compositions for topical application for the treatment of allergic diseases of the eye and nose

The invention relates to medicine, specifically to pharmacology

The invention relates to substituted derivative asalaam, which is an effective anti-Helicobacter tools that can be used as monotherapy for eradication of Helicobacter pylori and related species