Method for treatment of depression with compound-agonists of delta-receptors

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compositions and methods for treatment of depressive disorder in subject using the therapeutically effective dose of agonist(s) of delta-receptors of the general formula: wherein Ar1 represents a 6-membered carbocyclic aromatic ring with a substitute Y at its carbon atom wherein Y represents carboxamide of the formula: CONR9R10 wherein both R9 and R10 represent ethyl group; Z is chosen from group consisting of hydrogen atom (H), -OH and alkoxy-group; Ar2 represents a 6-membered carbocyclic aromatic ring with a substitute X at its carbon atom wherein X represents H, or pharmaceutically acceptable ester or salt of such compound. Invention provides antidepressant effect in a patient in using indicated compounds in lower doses as compared with the known agonists of delta-receptors showing the related chemical structure with compounds proposed.

EFFECT: improved method of treatment, enhanced and valuable medicinal properties of compounds.

17 cl, 1 tbl, 21 ex

 

The text descriptions are given in facsimile form.

1. The way to deal with depressive disorder in a subject suffering from this disorder or are prone to it, in which the specified subject is administered an effective amount of a therapeutic composition comprising at least one compound selected from the group consisting of

where G=O-alkyl, N(alkyl)2and any other pharmaceutically acceptable esters,

and its pharmaceutically acceptable salts and esters.

2. The method according to claim 1, where the mentioned pharmaceutical composition is administered by way of introduction, selected from the group consisting of oral, rectal, local, sublingual, mucosal, nasal, ophthalmic, subcutaneous, intramuscular, intravenous, transdermal, spinal, vnutriobolochechnoe, intra-articular, intra-arterial, sub-arachnoid, bronchial, lymphatic, and intrauterine injection.

3. The method according to claim 1, where the specified therapeutic composition further comprises another agent to combat depressive disorder.

4. The method according to claim 3, where the specified another agent to combat depressive disorder includes an agent selected from the group consisting of tricyclic antidepressants, MAO inhibitors, agonists and antagonists of 5-HT, aminoketones, reuptake inhibitors of serotonin and adrenergic reuptake inhibitors.

5. Compo is ice to combat depressive disorder in a subject, suffering from this disorder or are prone to it, containing at least one compound selected from the group consisting of

where G=O-alkyl, N(alkyl)2and any other pharmaceutically acceptable esters,

and its pharmaceutically acceptable salts and esters.

6. The composition according to claim 5 in standard dosage form.

7. The composition according to claim 6, where the specified standard dosage form comprises an oral dosage form.

8. The composition according to claim 5, additionally containing another agent to combat depressive disorder.

9. The composition of claim 8, where the specified another agent to combat depression the m disorder includes the agent, selected from the group consisting of tricyclic antidepressants, MAO inhibitors, agonists and antagonists of 5-HT, aminoketones, reuptake inhibitors of serotonin and adrenergic reuptake inhibitors.

10. Composition for combating depressive disorder mood for a subject suffering from this disorder or are prone to it, containing bulletinvirginia compound of General formula

where Ar1represents a 6-membered carbocyclic aromatic ring with the carbon atom Deputy Y, where Y represents carboxamide formula CONR9R10where R9and R10both represent ethyl group;

Z is selected from the group consisting of hydrogen, hydroxyl and alkoxy; and

Ar2represents a 6-membered carbocyclic aromatic ring with the carbon atom Deputy X, where X represents hydrogen,

or its pharmaceutically acceptable ester or salt.

11. The composition of claim 10, where bulletinvirginia compound is administered in oral dosage form.

12. The composition of claim 10, further containing another agent to combat depressive disorder.

13. The composition of claim 10, further containing another agent on what I struggle with depressive disorder, which is not an agonist of opioid receptor Delta.

14. The composition according to item 12, where specified another agent to combat depressive disorder includes an agent selected from the group consisting of tricyclic antidepressants, MAO inhibitors, agonists and antagonists of 5-HT, aminoketones, reuptake inhibitors of serotonin and adrenergic reuptake inhibitors.

15. The way to deal with depressive disorder in a subject suffering from this disorder or are prone to it, in which the specified subject is administered an effective amount of a therapeutic composition containing bulletinvirginia compound of General formula

where Ar1represents a 6-membered carbocyclic aromatic ring with the carbon atom Deputy Y, where Y represents carboxamide formula CONR9R10where R9and R10both represent ethyl group;

Z is selected from the group consisting of hydrogen, hydroxyl and alkoxy; and

Ar2represents a 6-membered carbocyclic aromatic ring with the carbon atom Deputy X, where X represents hydrogen,

or its pharmaceutically acceptable ester or salt.

16. The method according to clause 15, where the composition to omnitele contains another agent to combat depressive disorder.

17. The method according to clause 16, where another agent to combat depressive disorder selected from the group consisting of tricyclic antidepressants, MAO inhibitors, agonists and antagonists of 5-HT, aminoketones, reuptake inhibitors of serotonin and adrenergic reuptake inhibitors.



 

Same patents:

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compound of the formula (I): wherein (a) each R1 is chosen independently from hydrogen atom and alkoxy-group; (b) R2 represents hydrogen atom; (c) each R3 and R4 is chosen independently of one another from hydrogen atom, alkyl, alkynyl, heteroalkyl group, aryl; or R3 and R4 in common with nitrogen atom bound with them form heteroaryl or heterocycloaryl substitute optionally substituted with one or more hydroxo-group, carboxyl group, keto-, thioketo-, phenyl group, alkyl, heteroalkyl group, heteroaryl, heterocycloalkyl, spirocycloalkyl and their combinations; (d) each R5 and R6 represents hydrogen atom; or optical isomers, diastereomers and enantiomers represented by above given formula, and their pharmaceutically acceptable salts also. Also, invention describes using compound of the formula (I) for preparing a pharmaceutical composition possessing antibacterial activity and antibacterial pharmaceutical composition containing the safety and effective amount of compound of the formula (I) and a pharmaceutically acceptable carrier. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable properties of compounds and pharmaceutical composition.

7 cl, 37 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes derivatives of aminotetraline of the formula (I) wherein R1 means (C1-C6)-alkyl; R2 means halogen atom or -OR'; R3 means hydrogen atom (H) or -OR' wherein R' means (C1-C6)-alkyl or -SO2R'' wherein R'' means phenyl, thienyl, isoxazolyl; R4 means (C1-C6)-alkyl, phenyl, piperidinyl, pyrrolidinyl, morpholinyl, piperazinyl, diazepinyl, furanyl, isoxazolyl, imidazolyl and pyrazolyl that can be substituted optionally, and pharmaceutical compositions containing derivatives of aminotetraline. Proposed compounds are selective antagonists of M2/M3 muscarinic receptors and designated for treatment and prophylaxis of diseases associated with smooth muscle disorder.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

23 cl, 1 tbl, 16 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to alkylated (1H-benzimidazol-5-yl)-(-4-substituted phenyl)-amine derivatives, in particular compound of formula and pharmaceutically acceptable salts or solvates thereof, wherein R1, R2, and R9, are independently hydrogen, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluorimethoxy, azido, etc.; R7 is optionally substituted C1-C10-alkyl, C3-C10-cycloalkyl, etc.; A is-OR3 or NR4R3; R8 is hydrogen, -Cl, -Br, -F, cyano, nitro, etc.; and meanings of the rest substituents are as defined in specification. Also disclosed is composition for MEK inhibition and uses of benzinidazole compounds.

EFFECT: new compounds with value biological properties.

32 cl, 56 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new pyrasole derivatives of formula I wherein R5 represents phenyl or heteroaryl ring of formulae IIIa-IIIh meanings of the rest substituents are as defined in specification. Also disclosed are pharmaceutical composition based on said derivatives of formula I and uses thereof.

EFFECT: new biologically active compounds and pharmaceutical compositions based on the same for HIV inhibition.

13 cl, 54 ex, 2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): wherein R means -C(O)R1 wherein R1 is chosen from the series: (C1-C6)-alkyl, -C=CH-COOH, -NHCH2-CH2R2, -N(CH2-CH2OH)CH2-CH2OH, -N(CH3)CH2-CH2-NHCH3, -N(CH3)CH2-CH2N(CH3)CH3, saturated 4-, 5- and 6-membered cycles and saturated and unsaturated 5- and 5-membered cycles comprising at least one heteroatom from a series sulfur (S), nitrogen (N) and oxygen (O), and optionally substituted with a group chosen from the series: (C1-C6)-alkyl, -C=O-R5, -OH, (C1-C6)-alkyl substituted with hydroxy-group optionally, (C1-C6)-alkyl substituted optionally with a group of the series: -NH2, -N-(C1-C6)-alkyl, -SO2CH3, =O, and 5- and 6-membered saturated cycles comprising at least one heteroatom chosen from N and O, and wherein R5 is chosen from the series: hydrogen atom (H), (C1-C6)-alkyl, (C1-C6)-alkyl substituted with hydroxy-group optionally, and (C1-C6)-alkyl substituted with NH2-group optionally; R2 is chosen from the series: -N(CH3)CH3, -NH2, morpholinyl and piperazinyl; X1, X2 and X3 are chosen independently from the series: -OH, (C1-C2)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CH2OCH3 and -CH2OCH2CH3, or one among X1, X2 or X3 means hydrogen atom, and two others are chosen independently from the series: hydroxy-group, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -Cl, -Br, -F, -CF3, -CH2OCH3, -CH2OCH2CH3, -OCH2-CH2R3, -OCH2-CF3 and -OR4, morpholylmethyl, -N(CH3)CH3, -CH2OH, -COOH, or one among X1, X2 or X3 means hydrogen atom, and two others in common with two carbon atoms including bonds between them in benzene cycle to which they are bound optionally form 5- or 6-membered saturated cycle comprising at least one heteroatom chosen from S, N and O, and wherein R3 is chosen from the series: -F, -OCH3, -N(CH3)CH3, saturated 5-membered cycle comprising at least one heteroatom N; R4 means 3-5-membered saturated cycle, and each Y1 and Y2 is chosen independently from the series: -Cl, -Br, -NO2,-C≡N and C≡N, and compound of the formula (II) also given in the invention description. Also, invention relates to a pharmaceutical composition possessing anti-proliferative activity and based on these compounds. Invention provides preparing novel compounds possessing the useful biological properties.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

28 cl, 39 ex

Novel benzodioxols // 2304580

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel derivatives of benzodioxol of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7 and X are given in the description and the invention claim, and to their pharmaceutically acceptable salts. Also, invention relates to pharmaceutical compositions based on compounds of the formula (I) and their using for preparing medicinal agents used in treatment and/or prophylaxis of diseases associated with modulation of CB1 receptors.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 279 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention relates to varioline derivatives of general formula (5a), wherein R1 is selected from halogen and C1-C12-alkyl; R2 is selected from hydrogen and halogen; R3, R4, R5, R6, and R7 represent hydrogen; X1 amino group optionally substituted by C1-C12-alkoxy, benzylamino, C1-C12-alkylsulfinyl, or C1-C12-thioalkyl; X2 amino group, C1-C12-thioalkyl, C1-C12-alkylsulfinyl, or optionally C1-C12-alkoxy-substituted benzylamino; or R1 and R2 pair can be combined into condensed benzene ring system optionally substituted by C1-C12-alkoxy group. Indicated compounds exhibit antitumor activity. Invention further relates to pharmaceutical composition based on these compounds and use of these compounds to prepare drug useful in treatment of cancer. Invention also comprises a method for preparing intermediate varioline compounds. .

EFFECT: expanded synthetic possibilities in heterocyclic compounds area and increased choice of antitumor agents.

16 cl, 107 ex

FIELD: organic chemistry, medicine, endocrinology, pharmacy.

SUBSTANCE: invention describes novel derivatives of hexahydrodiazepinone of the general formula (I): or their pharmaceutically acceptable salts wherein Ar represents phenyl substituted with one-three halogen atoms; R1 means hydrogen atom, (C3-C6)-cycloalkyl possibly substituted with hydroxy-group, halogen atom, (C1-C10)-alkoxycarbonyl or phenyl-(C1-C3)-alkoxy-group; R4 means hydrogen atom, (C1-C10)-alkyl optionally substituted with: (a) phenyl that can be substituted with halogen atom, (C1-C3)-alkyl, halogen-(C1-C3)-alkyl, halogen-(C1-C3)-alkoxy-group; (b) hydroxy-group; (c) (C3-C6)-cycloalkyl; (d) phenyl-(C1-C3)-alkoxy-group; (e) biphenyl; (f) pyridyl; (g) 1-oxido-pyridinyl; (i) pyrazolyl; R5 means hydrogen atom or (C1-C10)-alkyl; R8 and R9 mean hydrogen atom. Also, invention relates to a pharmaceutical composition containing these compounds and using novel compounds for preparing a medicinal agent used in treatment of non-insulin dependent diabetes mellitus.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 2 tbl, 9 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to N3-alkylated benzimidazole derivatives for preparing a drug used in inhibition of MEK activity. Invention describes benzimidazole compound of the formula (I): and its pharmaceutically acceptable salts and solvates wherein R1, R2, R9 and R10 are chosen independently from hydrogen atom, halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-, azido-group, -OR3, -C(O)R3, -C(O)OR3, -OC(O)R3, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group; R3 is chosen from hydrogen atom, trifluormethyl group, (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl group is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R', -C(O)OR', -OC(O)R' wherein R' is chosen independently from hydrogen atom, lower alkyl; R4 represents independently hydrogen atom or (C1-C6)-alkyl; R6 is chosen from trifluoromethyl group or (C1-C10)-alkyl, (C3-C10)-cycloalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R', -C(O)OR', -OC(O)R', -OR'; R7 is chosen from (C1-C10)-alkyl, (C3-C10)-cycloalkyl, (C3-C10)-cycloalkylalkyl wherein each alkyl and cycloalkyl moiety is substituted possibly with groups in the amount from one to five and chosen independently from halogen atom, trifluoromethyl group, difluoromethoxy-, trifluoromethoxy-group, -C(O)R3, -C(O)OR3, -OC(O)R3, -SO2R6, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl; W is chosen from -C(O)OR3, -C(O)NR3R4, -C(O)NROR3, -C(O)R4OR3, -C(O)(C3-C10)-cycloalkyl, -C(O)(C1-C10)-alkyl. Also, invention describes compositions used for inhibition of MEK activity, using such compounds for preparing a drug used in inhibition of MEK activity and preparing a drug used in cancer treatment.

EFFECT: valuable medicinal and biochemical properties of compounds and composition.

17 cl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of cyclic amine of the general formula (1): , their pharmaceutically acceptable salts or hydrates wherein each among R1, R2 and R3 represents independently hydrogen atom, halogen atom, hydroxy-group, (C1-C8)-alkoxy-group; each among W1 and W2 represents independently nitrogen atom (N) or -CH; X represents oxygen atom (O), -NR4, -COONR4 or -NR4CO; R4 represents hydrogen atom, (C1-C8)-alkyl, (C3-C6)-alkynyl, substituted or unsubstituted phenyl, unsubstituted benzyl, unsubstituted indanyl wherein substitute(s) of phenyl represent(s) 1-3 groups or atoms chosen from (C1-C8)-alkyl, (C1-C8)-alkoxy-group, (C1-C8)-alkoxy-group substituted with 1-3 halogen atoms, (C1-C8)-alkylthio-group, (C1-C8)-alkylsulfonyl, halogen atom, trifluoromethyl group and (C1-C3)-alkylenedioxy-group; each among l, m and n represents number 0 or 1. Proposed compounds possess inhibitory effect on cell adhesion and/or cell infiltration and can be used as a medicinal agent and pharmaceutical composition based on thereof.

EFFECT: valuable biological and medicinal properties of compounds and pharmaceutical composition.

6 cl, 1 tbl, 439 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of formula I , wherein G is carbon or nitrogen atom; A is i) phenyl substituted with any from -COOH, -CONH2, COOCH3, -CN, -NH2 or -COCH3; ii) naphthyl, benzophuranyl, and quinolinyl; and iii) formulae , , .

Compounds of present invention are useful in particular in pain treatment.

EFFECT: new agents for pain treatment.

58 ex

FIELD: organic chemistry.

SUBSTANCE: claimed method includes reaction of C60-fullerene with 1,2-diaminepropane in presence of Cp2TiCl2 as catalyst in toluene medium at room temperature (approximately 20°C) for 44-52 hours. Yield of target product is 73-90 %. Compound of present invention is useful as chelating agent, sorbent, biologically active compound and for production of new materials with desired electronic, magnetic and optical properties. .

EFFECT: new compound; method of increased yield and selectivity.

1 tbl, 1 ex

FIELD: organic chemistry, medicine, ophthalmology, pharmacy.

SUBSTANCE: invention relates to new derivatives of nitrogen-containing heterocyclic compounds of the general formula (I): wherein X1, X2, X3, X4 and X5 mean -CH2 or one of them represents -NH and another X1-X5 represent -CH2; k = 0, 1 or 2; when t = 2, then radicals R1 are similar or different; R1 represents direct or branched (C1-C8)-alkyl or (C1-C8)-alkoxy-group; A means phenyl or pyridinyl; R2 means hydrogen atom (H), hydroxyl, halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy-group; n = 0, 1-4; radicals R2 are similar or different, when n > 1; p = 0 or 1-5; Y means -OC(O); Z means -CH, or to their pharmaceutically acceptable salts. Compounds of the formula (I) possess agonistic activity with respect to muscarinic receptors and can be used in medicine as medicinal preparations for treatment of neurodegenerative diseases or diseases associated with increased intraocular pressure.

EFFECT: valuable medicinal properties of derivatives.

6 cl, 1 tbl, 2 dwg, 16 ex

The invention relates to peptide compositions with delayed release, representing a compound (I) containing the compound (A) formula

and the polymer containing lactide links, glycolide links and links tartaric acids - which are found in the polymer at the next sootnoshenii: lactide units constitute from about 71% to about 73%, glycolide links from about 26% to about 28%; and the parts of tartaric acid from about 1% to 3%, and the amino group of the compound (a) relate ionic bond with the carboxyl groups of the acid units of the polymer; the particles of compound I, an average size of from about 10 microns to about 100 microns; pharmaceutical composition with delayed release and two methods of treatment of various diseases, including the introduction to the patient an effective amount of compound A, or microparticles

The invention relates to new derivatives of nitrogen-containing heterocyclic compounds of General formula

where X1-X5denote SN2or one of them denotes NH, and the other X1-X5are CH2; k is 0 or 1, R1is1-8the alkyl, C1-8hydroxyalkoxy; t is 0, 1 or 2; And represents phenyl or pyridinyl; R2is H, hydroxyl, halogen or1-6the alkyl, C1-6alkoxygroup; n is 0, 1-4; p is 0 or an integer from 1 to 5, Y is-C(O)-; Z is CH2or their pharmaceutically acceptable salts

The invention relates to derivatives of piperazine or piperidine derivatives of General formula I, in which G represents a carbon atom or nitrogen; And selected from (i) phenyl substituted by a group-COOH, CONH2-SOON3, -CN, NH2or-PINES3; (ii) naphthyl, benzofuranyl and hineline; or a group of the formula (iii), R1selected from hydrogen; branched or straight C1-C6of alkyl, C1-C6alkenyl - (C1-C6alkyl); each of R9, R10, R13, R14, R17and R18independently has the meanings indicated above for R1; Represents a substituted or unsubstituted aromatic, optionally substituted C5-C10hydroaromatics balance
The invention relates to a method for producing 2-trifluoromethyl-10-[3-(1-methyl-piperazinil-4)-propyl)] -fenotiazina used to treat diseases of the Central nervous system

FIELD: chemical technology, pharmacy.

SUBSTANCE: invention relates to an improved method for preparing sertraline hydrochloride form V that possesses the antidepressant effect. Method involves the following steps: (a) dissolving or suspending sertraline mandelate in a protonic solvent or a mixture of protonic solvents; (b) decreasing pH value of solution or suspension by addition of HCl aqueous solution of HCl solution in protonic solvent with addition of water to form a clear solution, and (c) isolation of the sertraline hydrochloride form V. At step (a) solvents from group comprising alcohol, water or their mixtures are chosen as solvents. For example, an alcoholic solvent used in step (a) can be chosen from group comprising methanol, ethanol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, tert.-butyl alcohol and isobutyl alcohol or their mixtures but isopropyl alcohol is preferable. The dissolving or suspending step (a) is carried out at heating and/or stirring in solvent at temperature in the range 20-90oC usually. Decreasing the pH value in step (b) is carried out usually up to the range 1-3 preferably. Sertraline hydrochloride form V obtained at step (c) is isolated by cooling the mixture obtained at step (b). Cooling is carried out under natural conditions to room temperature or using mild cooling agents, such as cold water, water, alcohol or their mixtures wherein indicated alcohol is chosen from group comprising monohydric alcohol, dihydric alcohol or their mixtures. Also, invention relates to a method for preparing a pharmaceutical composition with immediate releasing the sertraline hydrochloride form V that involves mixing sertraline hydrochloride form V prepared by cl. 1 having particles size less 20 mcm and in the amount 90% of the total amount of particles, not less, with a pharmaceutically acceptable diluting agent, carrier or carrier. Proposed method provides simplifying the process for preparing the preparation based on decreasing the total amount of steps.

EFFECT: improved preparing method.

14 cl, 4 sch, 2 dwg, 1 tbl

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