Derivatives of benzoxazolone, pharmaceutical composition and treatment methods

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to new derivatives of phenylpiperazine that are partial agonists of D2 receptors and can be used in treatment of the central nervous system disorders, in particular, Parkinson's disease. Invention describes derivatives of benzoxazolone of the formula (1): wherein R means group of the formula (a) or (b) , and their salts. Also, invention describes a method for preparing compounds of the formula (1), pharmaceutical composition based on compounds of the formula (1), method for treatment of Parkinson's disease and method for treatment of the central nervous system disorders, such as schizophrenia, anxiety state and depression based on compounds of the formula 91). Invention provides preparing new compounds possessing the useful biological properties.

EFFECT: improved methods for treatment, valuable medicinal properties of compounds and pharmaceutical composition.

5 cl, 1 tbl, 2 ex

 

The invention relates to new derivatives phenylpiperazine formula (1):

where:

- R means a group of formula (a) or (b)

and their salts.

Found that the compounds according to the invention exhibit high affinity to the dopamine D2 receptor and the site re-absorption of serotonin. This combination is suitable for the treatment of psychotic diseases such as schizophrenia (treatment of both positive and negative symptoms) and other psychiatric diseases.

The compounds exhibit activity as a (partial) agonists, which makes them suitable for the treatment of Parkinson's disease.

The compounds exhibit activity of antagonists to the receptors of dopamine D2as they antagonizing caused by apomorphine in mice behavior glassing. The compounds also show activity as inhibitors of reuptake of serotonin, as they enhance the mice behavior induced by 5-HTP.

These compounds are active in therapeutic models that are sensitive to clinically relevant antipsychotic agents (for example, the reaction conditioned reflex avoidance; Van der Heyden & Bradford, Behav. Brain Res., 1988, 31: 61-67) and antidepressants or anxiolytics (for example, the suppression caused by the article is the ECCA cries; van der Poel and other Psychopharmacology, 1989, 97: 147-148).

Compounds active in clinically relevant models for Parkinson's disease (for example, changing the behavior of the rats; U. Ungerstedt, Acta Physiol. Scand., 1971, 82 (Appendix 367): 69-93).

In contrast to the clinically relevant receptor antagonists dopamine D2described compounds have a low propensity to induce catalepsy in rodents and thus likely to induce less extrapyramidal side effects than existing antipsychotics.

Inhibiting activity of re-absorption of serotonin, characteristic of these compounds may be responsible for therapeutic effects observed in behavioral models that are sensitive to antidepressants or anxiolytics.

Connections can be used to treat lesions or diseases of the Central nervous system, caused by violations of either dopaminergic or serotonergic systems, such as aggression, anxiety, autism, vertigo, depression, disorders of cognitive ability or memory, Parkinson's disease, and schizophrenia and other psychotic disorders.

Pharmacologically acceptable acids which the compounds of the invention can form a suitable acid additive salts are, for example, chloritoid the native acid, sulfuric acid, phosphoric acid, nitric acid and organic acids such as citric acid, fumaric acid, maleic acid, tartaric acid, acetic acid, benzoic acid, para-toluensulfonate, methanesulfonate and naphthalenesulfonate.

Compounds and their acid additive salts can be produced in forms suitable for injection, using appropriate methods when using additional substances, such as liquid and solid media.

Compounds having the formula (1)can be obtained by reaction of compounds of formula

in basic conditions with a compound of formula L(a) or L-(b)

where formula (a) and (b) have the above meanings and L is the so-called tsepliaeva group such as halogen atom or mutilata group.

Pieperazinove compound of the formula (2) can be obtained as described in patent EP 0189612.

Educt of the formula L-(a) may be obtained according to the following scheme:

Scheme And

Connection R can be obtained from R in the same way as the connection R, that is, the compound L-(b), where L means mesilate group of compounds R (see chart below).

Schema

The invention is illustrated by the following example is I.

Example 1

of 18.1 g (0.1 mol) R was dissolved in 250 ml of CH2Cl2and brought up to 0°C. To the solution in CH2Cl2was added a solution prepared from 50 ml of concentrated sulfuric acid, wulitou on 200 g of ice. The resulting mixture was stirred at 0°using a cooling bath of ice/acetone. The last solution was added dropwise to 8.3 g (0.12 mol) NaNO2dissolved in 50 ml of water, and the temperature was maintained below 2°C. the Stirring was continued for 1 hour. Then the organic layer was separated, the aqueous layer once were extracted (CH2Cl2), the combined organic fractions were dried over MgSO4. The desiccant was removed by filtration and the filtrate was concentrated in vacuum, obtaining 17.8 g (99%) of crude dark yellow R. A solution of 17.8 g (0,099 mol) R in 100 ml dry THF under nitrogen atmosphere very carefully added dropwise to a suspension of LiAlH4(9.75 g, 244 mmol) in boiling dry THF. After completion of addition, the mixture was left to react for another 40 minutes. The reaction mixture was brought to room temperature and then cooled in a cooling bath of ice/ethanol. Then he added: 9.75 ml of water/THF (1/1), and 18.5 ml of 2n. NaOH (aq.) and 18.5 ml of water. The resulting mixture was brought to boiling for 20 minutes. After cooling, the reaction mixture was filtered (Hyflo), the obtained filtrate was concentrated in vacuum, obtaining 15.9 g of residue. After the deposits were dissolved in 98 ml of 1N. HCl in EtOAc, the resulting precipitate was filtered, receiving of 17.5 g (87%) R·HCl.

17.5 g (86 mmol) 2p3·HCl was dissolved in a mixture of 190 ml of ethylene glycol and 90 ml of water, the resulting solution was heated to 95°C. Then carefully added dropwise of 7.96 g (a 94.6 mmol) (3,4)-dihydro-2H-Piran. After completion of addition, stirring was continued for 3 hours at 95°C. After the reaction mixture had reached room temperature, added water and a little brine and was extracted with EtOAc (3×). The combined organic fractions were washed with water, NaHSO4(aq.), NaCl(aq.) accordingly, after which the organic fraction was dried over Na2SO4. Removal of drying agent and solvent gave a residue, which was purified column chromatography (SiO2, eluent Meon/CH2Cl23/97)to give 12 g (63%) of a dark red oil containing the corresponding alcohol R, which hardened on standing. Then the alcohol was converted into mesilate in the standard way (MsCl, diisopropylethylamine in CH2Cl2, 0° (C)receiving R (yield 98%).

Phenylpiperazin having the formula (2)were subjected to interaction with R according to the method described in patent EP 0900792, to obtain the compounds (1), where R denotes a group of formula (b); (TPL: 182-5°).

Example 2

R turned in R like getting R (example 1). R turned in R (98%) according to the method, described RajanBabu and others, J.Org.Chem. 51, (1986), 1704.

31,9 g (103 mmol) R in nitrogen atmosphere was dissolved in 49 ml of DMF. The resulting solution was slowly added to the solution containing 5,88 g (134 mmol, 1.3 EQ.) oil suspension containing 55% NaH in 148 ml of DMF, after which stirring is continued for one hour at room temperature, then the reaction mixture was cooled (ice/water). The last solution was added dropwise to 8.34 ml (19,02 g, 134 mmol, 1.3 EQ.) MeI dissolved in 49 ml of DMF. The reaction mixture was stirred an additional 16 hours at room temperature. The last was added water and was extracted with Et2O (2×), the organic fraction was washed with water (2×) and brine (1×) and finally dried over MgSO4. After removal of the desiccant and solvent in vacuo the residue was subjected to column chromatography (SiO2, eluent: CH2Cl2/hexane 3/1), getting to 26.2 g (79%) R in the form of a yellowish oil.

25,03 g (78 mmol) R was dissolved under nitrogen atmosphere in 110 ml of THF, and then added 93 ml (0,93 mmol, 1.2 EQ.) 1H. (n-But)4N+F-in THF. After stirring for one hour was added Et2O and the resulting mixture was washed with water (3×) and brine (1×). The organic layer was dried over Na2SO4. After removal of the desiccant and solvent the residue was extracted with toluene and then concentrated in vacuum to UDA is possible traces (t)butyldimethylsilyloxy. The residue was subjected to flash chromatography (SiO2, eluent Et2O), eventually getting 14.8 g (92%) R.

1,69 g (6,45 mmol) PPh3and 0.44 g (6,44 mmol) of imidazole was dissolved in 20 ml of CH2Cl2then the portions was added 1.64 g (6,45 mmol) of iodine. The reaction mixture was stirred for another 30 minutes at room temperature. To the latter mixture was slowly added 1.07 g (5,16 mmol) R dissolved in 10 ml of CH2Cl2. After 30 minutes the reaction mixture was washed with NaHCO3(aq.), NaHSO3(aq.) and brine, the remaining organic fraction was dried over Na2SO4. After removal of the desiccant and solvent in vacuo the residue was dissolved in Et2O, the precipitate (Ph3PO) was removed by filtration. The filtrate was concentrated in vacuo, the residue was purified flash chromatography (SiO2, eluent: CH2Cl2/hexane 1/1)to give 1.45 g (88%) of the desired iodide R.

Phenylpiperazin having the formula (2)were subjected to interaction with R according to the method described in patent EP 0900792, with connection 1, where R is the group (a) (TPL: 202-4°).

Table

Pharmacological data for the compounds of formula (1):
R
Pharmacological analysisIndicator / Edenism.Example 2Example 1
Affinity in vitro
The affinity to the receptor dopamine D2pKi8,28,6
Site of absorption of serotoninpKi>9,0
Functional activity in vitro
agonism in respect of the receptor dopamine D2(camp-test)pEC506,0
internal activity against receptor dopamine D2(0,0-1,0)ε0,310,27
the uptake of 5-HT by synapse in rat brainpEC507,2
Inhibition of the uptake of 5-HT in vivo
Potentiation of 5-NTR of seroma oralED50mg/kg11,1
Activity against Parkinson's disease in vivo:
changing the behavior of rats 6-OHDA, oralED50mg/kg11,0

1. Derivatives benzoxazolone having the formula (1)

where R denotes a group of formula (a) or (b)

and their salts.

2. Method of preparing compounds according to claim 1, characterized in that the compound having formula (2),

subject interaction in basic conditions with a compound of formula L(a) or L-(b)

where L means tsepliaeva group, and (a) and (b) have the meanings given in claim 1.

3. Pharmaceutical composition for the treatment of CNS disorders, such as schizophrenia, anxiety, depression, and Parkinson's disease, containing at least one compound according to claim 1 as an active ingredient.

4. JV is a method for treating Parkinson's disease, wherein the applied compound according to claim 1.

5. A method of treatment of CNS disorders, such as schizophrenia, anxiety and depression, wherein the applied compound according to claim 1.



 

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29 cl, 12 tbl, 587 ex

FIELD: organic chemistry, medicine, endocrinology.

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52 cl, 77 ex

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(2)

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EFFECT: valuable properties of compounds.

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EFFECT: valuable medicinal and biochemical properties of compounds.

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EFFECT: improved and valuable pharmaceutical properties of agent.

22 cl, 32 dwg, 7 tbl, 28 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds and composition.

7 cl, 16 ex

FIELD: organic chemistry, medicine, pharmacology, pharmacy.

SUBSTANCE: invention relates to a new physiologically active composition effecting on nicotine receptors and prepared in the form of tablets, granules, capsules, suspensions, solutions and injections. As an active component the composition comprises pharmaceutically effective amount of substituted 1-oxo-1,2-dihydro[2,7]-naphthyridine of the general formula (1)

or its salt, N-oxide or hydrate wherein R1 represents hydrogen atom, inert substitute, optionally substituted (C1-C5)-alkyl, optionally substituted amino-group; R2 and R3 represent independently of one another hydrogen atom, nitrile group, formyl group, inert substitute, optionally substituted (C1-C5)-alkyl, carboxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group or optionally substituted carbamoyl group; R4 at carbon atoms of pyridine moiety represents: hydrogen atom, halogen atom, inert substitute, optionally substituted hydroxy-(C1-C5)-alkyl, optionally substituted amino-group, optionally substituted hydroxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group, optionally substituted carbamoyl group; R4 at nitrogen atom of pyridine moiety forms pyridinium salt with pharmacologically acceptable anion and represents inert substitute. Also, invention relates to new substituted 1-oxo-1,2-dihydro[2,7]naphthyridines of the general formula (1) or their salts, N-oxides or hydrates wherein R1 and R4 have value given in cl. 1, and R2 and R3 represent independently of one another carboxyl group, optionally substituted (C1-C6)-alkyloxycarbonyl group or optionally substituted carbamoyl group. Also, invention relates to a method for their preparing and to a method for modulating activity of nicotine receptor and using compounds of the general formula (1) by cl. 1 for preparing physiologically active composition, and as ligands of nicotine receptors for aims of experimental investigations of physiological processes as "pharmacological tools". Also, invention relates to a set for preparing the composition.

EFFECT: improved preparing method, valuable properties of compounds and compositions.

7 cl, 2 sch, 2 tbl, 5 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

FIELD: medicine, pharmacology.

SUBSTANCE: invention relates to arypyprazole anhydrous crystals B showing characteristic peaks in powdered roentgen rays diffraction at 2θ = 11.0°, 16.6°, 19.3°, 20.3° and 22.1°, specific infrared absorption bands at 2945, 2812, 1678, 1627, 1448, 1377, 1173, 960 and 779 cm-1 in IR-spectrum, endothermic peak at 141.5° in thermogravimetric/differential thermic analysis and endothermic peak at 140.7° C in differential scanning calorimetry, arypyprazole A hydrate, to methods for their preparing, pharmaceutical compositions comprising arypyprazole crystals B and methods for their preparing. Invention provides reduced hygroscopicity of arypyprazole crystals B.

EFFECT: improved preparing method.

57 cl, 14 tbl, 24 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepines of the general formula (I):

wherein X means ordinary bond or ethynediyl group wherein if X mean ordinary bond then R1 means halogen atom or phenyl substituted with halogen atom optionally or (C1-C7)-alkyl group; in case when X means ethynediyl group then R1 mean phenyl substituted with halogen atom optionally; R2 means halogen atom, hydroxy-group, lower alkyl, lower alkoxy-group, hydroxymethyl, hydroxyethyl, lower alkoxy-(ethoxy)n wherein n = 1-4, cyanomethoxy-group, morpholine-4-yl, thiomorpholine-4-yl, 1-oxothiomorpholine-4-yl, 1,1-dioxothiomorpholine-4-yl, 4-oxopiperidine-1-yl, 4-(lower)-alkoxypiperidine-1-yl, 4-hydroxypiperidine-1-yl, 4-hydroxyethoxypiperidine-1-yl, 4-(lower)-alkylpiperazine-1-yl, lower alkoxycarbonyl, 2-di-(lower)-alkylaminoethylsulfanyl, N,N-bis-(lower)-alkylamino-(lower)-alkyl, (lower)-alkoxycarbonyl-(lower)-alkyl, (lower)-alkylcarboxy-(lower)-alkyl, lower alkoxycarbonylmethylsulfanyl, carboxymethylsulfanyl, 1,4-dioxa-8-azaspiro[4,5]dec-8-yl, carboxy-(lower)-alkoxy-group, cyano-(lower)-alkyl, 2-oxo[1,3]dioxolane-4-yl-(lower)-alkoxy-group, 2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrole-5-yl, (3R)-hydroxypyrrolidine-1-yl, 3,4-dihydroxypyrrolidine-1-yl, 2-oxooxazolidine-3-yl, carbamoylmethyl, carboxy-(lower)-alkyl, carbamoylmethoxy-, hydroxycarbamoyl-(lower)-alkoxy-, lower alkoxycarbamoyl-(lower)-alkoxy-, (lower)-alkylcarbamoylmethoxy-group; R3 means phenyl, thiophenyl, pyridinyl that are substituted with halogen atom, cyano-group, carbamoyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl wherein groups of 1,2,3-triazolyl, 1,2,4-triazolyl or isoxazolyl are substituted optionally with (C1-C7)-alkyl or (C1-C7)-alkylsulfanyl, and to their pharmaceutically acceptable salts. Also, invention describes a medicinal agent that is antagonist of mGlu receptors of the group II based on compound of the formula (I). The medicinal agent can be used in treatment and prophylaxis of acute and/or chronic neurological disturbances including psychosis, schizophrenia, Alzheimer's disease, disturbances in cognitive ability and memory damage.

EFFECT: valuable medicinal properties of compounds.

7 cl, 1 tbl, 98 ex

FIELD: organic chemistry, medicine, psychiatry, pharmacy.

SUBSTANCE: invention relates to medicinal agents used for prophylaxis and treatment of schizophrenia by inhibition or suppression of neurodegenerative disease caused by hypofunction of glutamic acid receptors. As an active component agents comprise derivative of 5-substituted 3-oxadiazolyl-1,6-naphthiridine-2(1H)-one of the formula (I):

wherein Het represents oxadiazolyl group; R1 represents hydrogen atom, lower alkyl group, lower cycloalkyl group, trifluoromethyl group, lower alkenyl group, lower alkynyl group, lower alkoxyl group, lower alkoxy-(lower)-alkyl group, lower hydroxyalkyl group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group; R2 represents hydrogen atom, lower alkyl group, lower cycloalkyl group, lower cycloalkylmethyl group, lower alkenyl group, lower cycloalkenyl group, lower alkynyl group, substituted or unsubstituted aryl group and substituted or unsubstituted heteroaryl group wherein indicated groups represent phenyl or naphthyl and indicated heteroaryl groups represents furyl, thienyl or pyridyl, or their physiologically acceptable acid-additive salts.

EFFECT: valuable medicinal properties of agents.

10 cl, 1 tbl

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of benzodiazepine of the general formula (I)

and their pharmaceutically acceptable acid-additive salts wherein X means a ordinary bond or ethynediyl group; when X means ordinary bond then R1 means halogen atom, (lower)-alkyl, (lower)-alkylcarbonyl, (lower)-cycloalkyl, benzoyl, phenyl substituted optionally with halogen atom, hydroxyl, (lower)-alkyl, (lower)-alkoxy-group, halogen-(lower)-alkoxy-group or cyano-group; styryl, phenylethyl, naphthyl, diphenyl, benzofuranyl, or 5- or 6-membered heterocyclic ring representing thiophenyl, furanyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl which are optionally substituted; when X means ethynediyl group then R1 means hydrogen atom, (lower)-alkyl substituted optionally with oxo-group; (lower)-cycloalkyl substituted with hydroxyl; (lower)-cycloalkenyl substituted optionally with oxo-group; (lower)-alkenyl, optionally substituted phenyl; 5- or 6-membered heterocyclic ring representing thiophenyl, thiazolyl, pyridinyl, dihydropyridinyl, tetrahydropyridinyl or dihydropyranyl and substituted optionally; R3 means phenyl, pyridyl, thiophenyl or thiazolyl which are substituted optionally. These compounds can be used for treatment or prophylaxis of acute and/or chronic neurological diseases, such as psychosis, schizophrenia, Alzheimer's disease, disorder of cognitive ability and memory disorder. Also, invention describes a medicinal agent based on these compounds and a method for preparing compounds of the formula (I).

EFFECT: improved method for preparing, valuable medicinal properties of compounds.

10 cl, 1 tbl, 173 ex

FIELD: medicine, pharmaceutical technology, pharmacy.

SUBSTANCE: invention relates to granulated composition containing 11-[4-[2-(2-hydroxyethyl)ethyl]-1-piperazinyl]dibenzo[b,f][1,4]thiazepine (quetiapine) or its pharmaceutically acceptable salt, preferably quetiapine fumarate, as an active substance and a water-soluble binding agent. Invention relates to a method for preparing this composition and to a method for treatment of patients with nervous system diseases such as psychotic states including schizophrenia. Invention alleviates dosing of drugs by patients in required dose and solves problem concerning maintenance of regimen and schedule of treatment.

EFFECT: improved and valuable properties of composition.

16 cl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves administering typical neuroleptics according to titration scheme and tricyclic antidepressants. Neuroleptics are applied according to titration scheme in the morning and tricyclic antidepressants are introduced as intravenous drop-by-drop infusion in the evening in combination with per os application of atypic neuroleptic risperidon. After having given 12-14 intravenous infusions, strategic supporting risperidon psychopharmacotherapy in combination with tricyclic antidepressants during 4-6 months.

EFFECT: enhanced effectiveness in overcoming pharmacological resistance; accelerated schizo-affective syndrome relief.

FIELD: medicine.

SUBSTANCE: invention proposes a medicinal preparation for treatment of extrapyramidal disorders (Parkinson's disease, dyskinetic and choreic syndromes, in particular, Huntington chorea, dystonic syndromes, later dyskinesia, tremor, Gilles de la Tourette's disease, ballism, fatigue legs syndrome and Wilson's disease), and a pharmaceutical composition and a set for the same designation also. As a medicinal preparation invention proposes (R)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chroman or its physiologically acceptable salt known early as a combined selective antagonist of dopamine D2 receptors and antagonist of serotonin receptor of 1A subtype. These properties and high affinity to D3 receptor show favorable effect on extrapyramidal and motor systems. Pharmaceutical composition and set comprise (R)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chroman or its salt and a medicinal preparation against Parkinson's disease as active compounds. The compound (R)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chroman decreased extrapyramidal moving disorders caused by neuroleptics and enhanced their anti-parkinsonic effect, i. e. it shows property to diminish symptoms of Parkinson's disease and to enhance the general activity.

EFFECT: improved and valuable medicinal properties of compound and pharmaceutical composition.

26 cl, 10 ex

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