Separation of the enantiomers of 5-hetaryl-1,3,4-thiadiazines

 

(57) Abstract:

Usage: in the pharmaceutical industry. The inventive enantiomers of 5-hetaryl-1,3,4-thiadiazines divided by the kinetic splitting of the racemate, which consists in the fact that the racemate 5-hetaryl-1,3,4-thiadiazine dissolved in an inert solvent or mixture of solvents, acelerou chiral acid chloride of the acid, the resulting mixture of diastereomers is treated with an amine, to full cleavage of a single diastereoisomer in enantiomers, which is the main, then separated from the fission products and the remaining pure diastereoisomer by reaction with the amine is transformed into the corresponding pure enantiomer. 1 C. p. F.-ly.

The invention concerns a method of separation of the enantiomers of 5-hetaryl-1,3,4-tradiational formula

(CO

(I) where R1means AND;

R2and R3respectively, H or A;

R4H, or acyl with 1 to 15 atoms WITH;

And alkyl with 1-8 C atoms;

n=1,2, or 3.

Derivatives of thiadiazine formula I is known from European patent N 0294647 and are specified as preferred.

R1-R4and a have the meanings specified under formula I, if there is no other explicit values.

Acyl is an acid residue of carboxylic or sulfonic acids, mainly alkaloid from 1 to 10, in particular 1, 2, 3, 4 or 5 C atoms, in some cases, preferably acetyl, further preferably formyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl (trimethylacetyl), further preferably optionally substituted aroyl with 7 to 15 C atoms, and as the substituents, in particular 1 to 3, mainly seen one of the following groups: alkyl, alkoxy, alkylthio, alkylsulfonyl or alkylsulfonyl with 1-3 respectively, mainly 1 or 2 atoms, methylendioxy, then HE, F, CL, Br, T, NR2, NH2alkylamino or dialkylamino with 1-3 respectively, mainly 1 or 2 atoms in the alkyl group. Individual preferred aroline residues are benzoyl, o-, m - or p-toluyl, o-, m - or p-methoxybenzoyl, 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-methylthiophenol, o-, m-, or p-methylsulfonylbenzoyl, o-, m - or p-methylsulfonylbenzoyl, 2 is ohms, for example 2 - or 3-furoyl, 2 - or 3-denial, pikolinos, nicotinoyl, isonicotinoyl, in addition, arylalkyl, for example, phenylacetyl, o-, m - or p-methoxyphenylacetyl, 2 - or 3-phenylpropionyl, 2-, 3 - or 4-phenylbutyric; cycloalkylcarbonyl, for example, cyclohexylcarbonyl; alkylsulfonyl, for example methyl-, ethyl-, propyl - or butylsulfonyl; arylsulfonyl, for example, bansilalpet, o-, m - or p-toluensulfonyl, -, m - or p-methoxybenzenesulfonyl, 1 - or 2 - naphthalenesulfonyl.

The separation of the racemate to the corresponding enantiomers hitherto possible only with the help of the method of liquid chromatography high pressure.

The objective of the invention to obtain the allocation method of enantiomers according to the formula I, do not use expensive separation using liquid chromatography high pressure, resulting in low yield of the target product, but at the same time ensuring the production of enantiomers of high purity in satisfactory quantities.

The problem is solved by using the kinetic method for the splitting of the racemate separation of the enantiomers of 5-hetaryl-1,3,4-thiadiazine.

Accordingly, the subject invention is a method of separation EN acelerou chiral acid chloride acid, the resulting mixture of diastereomers turn with the amine or alcohol, when this is complete splitting of a single diastereoisomer and minor splitting of the other diastereoisomer in enantiomers, which is the basis, then separated from the fission products and the remaining pure diastereoisomer by reaction with the amine or alcohol is transformed into the corresponding pure enantiomer.

A kinetic method for the splitting of the racemate, as a rule, does not satisfy the purity of the enantiomers and should be complemented with other methods.

In the case of compounds of formula I of the method can be applied without the use of additional methods, you get the purity of the enantiomers of more than 99%

The solvent is suitable mainly simple ether, such as tetrahydrofuran (THF), dioxane or a simple methyl tert-butyl ether, hydrocarbons such as hexane, cyclohexane, benzene, toluene, xylene or mesothelin, simple Picadilly ether, for example, a simple Picadilly or diethyl ether, amides, such as dimethylformamide (DMF), halogenated hydrocarbons such as dichloromethane, chlorobenzene or trichloroethylene, and mixtures of these solvents.

Especially predmety are for example, the acid chloride tetrahydro-5-oxo-2-frankenboob acid, acid chloride o-acetylindole acid, campolina acid or particularly preferably the acid chloride campanulas acid.

In particular, the racemate I is dissolved or suspended in one of these solvents or solvent mixtures, add an expedient manner, the base and the acid chloride of the acid, dissolved in one of these solvents, or in pure form. As bases are suitable, for example, hydroxides, carbonates, alcoholate of an alkali metal or alkaline-earth metals, in particular, secondary or tertiary amines, such as triethylamine or pyridine. Then the reaction mixture is stirred for 1-48 hours at a temperature between -20aboutC and the boiling point of the solvent, mainly in the range from -10 to +30aboutWith and produce a mixture of diastereomers. For cleavage of a mixture of diastereoisomers restore it in one of these solvents are mixed with the amine or alcohol, and again stirred for 1-48 h with 0-50aboutWith, mainly at 0-30aboutOr just stand.

It is also possible to dissolve the mixture of diastereomers without the use of additional rostamani With, in particular methanol, ethanol, or isopropanol, and mixtures thereof. Suitable amines, among others, piperidine, pyrrolidine, morpholin or ethylamine.

In the examples, "conventional treatment" means that, if necessary, add water or dilute sodium lye, extracted with an organic solvent, e.g. ethyl acetate, chloroform or dichloromethane, separated, the organic phase is dried over Na2SO4or gS4, filtered, evaporated and cleaned in appropriate circumstances advanced by chromatography or crystallization. The purity of the enantiomers can be determined, for example, using jhud or Differential scanning calorimetry (DSC). Reduction "Ehud" and "ei" refers to "liquid chromatography high pressure" and "enantiomer in excess".

P R I m e R 1. To a suspension of 40 g of 5-[1-(3,4-methylenedioxybenzyl)-1,2,3,4-tetrahydro-6-chinolin]-6-methyl-3,6-dihydro-2H-1, 3,4-thiadiazin-2-it in 800 ml of dichloromethane, diluted with 20 ml of trailmen added in drops with stirring at 0aboutWith 26 g of (-)-carboxylic campanulas acid dissolved in 100 ml dichloromethane and stirred for 4 h Then the reaction mixture is washed with hydrochloric acid and then bicarbonate restandol)-1,2,3,4-tetrahydro-6-chinolin] -6-methyl-3/6-dihydro-2H-1/3/4-televisin-2-it is in the form of a mixture of diastereomers, so pl. 216-217about.

P R I m m e R 2. 48 g of a mixture of diastereomers from example 1 are dissolved in 800 ml of tetrahydrofuran and after adding 3.6 ml of the research aged for 14 h at 25aboutC. the Reaction mixture was concentrated, stirred into water-ethyl acetate and, as usual, treated. (-)-Enantiomer obtained by splitting contaminated small amount of (+)-enantiomer is separated from the main number of unsplit diastereoisomer by chromatography. (+)-Enantiomer present in small quantities are removed from the (-)-enantiomer by recrystallization from ethanol in the form of a racemate. After concentration of the mother liquor and crystal - implementation of the receive(-)-5- [1-(3,4-methylenedioxybenzyl)-1,2,3,4-tetrahydro-6-Hino - Lil] 6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin - 2-it, so pl. 180aboutC; []20D=is 540about; ei > 99% (ghvd).

P R I m e R 3. 20 g of unsplit diastereoisomer of example 2 is dissolved in THF, diluted with 3 ml of the research and analogous to example 2, continue processing. After removal of solvent the residue precrystallizer from ethanol. Get(+)-5-[1-(3,4-methylenedioxybenzyl)-1,2,3,4 - tetrahydro-6-chinolin] 6-methyl-3,5-dihydro-2H-1,3,4-thiadiazin-2-it, so pl. 181aboutC; [] 20D= +to 541.5aboutC; []20D=+541,0about; ei > 99%

P R I m e R 5. Analogously to example 1 racemic mixture of 5-[1-methyl-1,2,3,4-tetrahydro-6-chinolin] -6-methyl-3,6-dihydro - 2H-1,3,4-thiadiazin-2-it (so pl. 177about(C) treated with (+)-acid chloride campanulas acid. Receive 3-[(+)-campanil] -5- (1-methyl-1,2,3,4-tetrahydro-6-chinolin)-6 - methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-it is in the form of a mixture of diastereoisomers.

P R I m e R 6. The mixture of diastereomers from example 5 is treated analogously to example 2 morpholine. Receive (+)-5-(1-methyl-1,2,3,4-tetrahydro-6-chinolin)-6-methyl - 3,6-dihydro-2H-1,3,4-thiadiazin-2-he, along with the corresponding unsplit the diastereoisomer, further processing as described in example 7.

P R I m e R 7. Unsplit the diastereoisomer of example 6 is dissolved as in example 4 in methanol and boiled for 20 hours After removal of the solvent the residue from ethanol and recrystallized receive (-)-5-(1-methyl-1,2,3,4-tetrahydro-6-chinolin)-6-me-til-3,6-dihydro-2H-1,3,4-t IADI

P R I m e R 8. Analogously to example 1 racemate 5-[1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydro-6-trimethoxybenzoyl)-1,2,3,4-tetrahed - ro-6-chinolin] 6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-it is in the form of a mixture of diastereoisomers. Similarly receive 3-[(+)-kapanol]-5-[1-isonicotinoyl-2,3, 4,5 - tetrahydro-1H-1-benzazepin-7-yl] -6-me - til-3,6-dihydro-2H-1,3,4-thiadiazin-2-it.

P R I m e R 9. The mixture of diastereomers from example 8 is treated analogously to example 2 morpholine. Get(-)-5-[1-(3,4,5-trimethoxybenzoyl)-1,2,3,4-tetrahydro-6 - chinolin]-6-methyl-3,6-dihydro-2H-1,3,4-t-aliasin-2-he, along with the corresponding unsplit the diastereoisomer, further processing as described in example 10.

Similarly, receive (-)-5-[1-isonicotinoyl-2,3,4,5-tetrahydro-1H-1-benzazepin-7-yl]-6-methyl-3,6 - digizen-2-it.

P R I m e R 10. From unsplit of the diastereoisomer of example 9 as in example 3 receive 9 (+)-5-[1-(3,4,5-trimethoxybenzoyl)-1,2,3,4-tetrahed - ro-6-chinolin] 6-methyl-3,6-dihydro-2H-1,3,4-thiadiazin-2-he, []20D=+476,2about.

Similarly receive (+)-5-[1-isonicotinoyl-2,3,4,5-tetrahydro-1H-1-benzazepin-7 - yl] -6-methyl-3,6-dihydro-2H-1,3,4-tiadi - Azin-2-he, []20D= +478,2about.

1. SEPARATION of the ENANTIOMERS OF 5-HETARYL-1,3,4-THIADIAZINES General formula I

< / BR>
where R1- A;

R2and R3- N or A;

R4- N, a or C1- C15-acyl;

A - C1-C8-alkyl;

n = 1, 2, or 3,

nerton solvent or mixture of solvents, acelerou chiral acid chloride of the acid, the resulting mixture of diastereomers is treated with an amine or alcohol to full cleavage of a single diastereoisomer and minor splitting of the other diastereoisomer in enantiomers, which is the basis, then separated from the fission products and the remaining pure diastereoisomer by reaction with the amine is transformed into the corresponding pure enantiomer.

2. The method according to p. 1, characterized in that the splitting of the diastereoisomer use methanol or morpholine.

 

Same patents:

The invention relates to new compounds 1,2,5,6-tetrahydropyridine number of General formula

(I) where Z is oxygen or sulfur;

R is hydrogen or C1-3-alkyl; when Z stands for oxygen, R1is a halogen, amino group, acetylamino or-O-R2where R2is4-6-alkyl or C6-quinil; Z, meaning sulfur, R1is halogen, C1-8-alkyl, C6-alkenyl straight chain, cyclopropylmethyl, benzyloxypropionic, morpholino-, 4-methylpiperidino - or 4-hexylamino or a group-O-R2where R2linear or branched C3-6alkenyl,3-6-quinil, cyclopropylmethyl, -R3-O-R4or-R3-O-R4-O-R5where each of R3, R4and R5means1-4-alkyl, or R1represents a group S-R2where R2linear C2-8-alkyl, or their pharmaceutically acceptable salts

The invention relates to a method for producing 6-fluoro-1,2-benzisothiazole formula

(I) where R is a hydrogen atom, a lower alkyl or a group of the formula

orwhere R1means-Cho or - CN, namely, that on-halogenoalkane derivative of the formula:

where R has the above meanings, is subjected to the interaction with R3SH, where R3- benzyl, environment aprotic organic solvent, with the formation of the compounds of formula

(III)where R and R3have the specified values, which are subjected to interaction with a halogenation agent to obtain the corresponding sulfanilamide formula

(IV)Subjected to interaction obtained sulfanilamide with ammonia in the compounds of the formula

(I)

Polucheniya pharmaceutically active compounds, which can be used, for example, as antipsychotic agents and as inhibitors of reuptake of serotonin

The invention relates to new heterocyclic compounds and their salts, as well as new intermediate products

Iap inhibitors // 2491276

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: U1-M-U2, where U1 and U2 have general formula (I), where: G stands for: IVb IVd ive, and values M, X1, X2, R2, R3, R3', R4, R4', R5, R5', R6, R6', R7, Z7, Z2, Z3, Z4, Q2 are given in item 1 of the formula.

EFFECT: compounds can be applied for induction of apoptosis in cell.

37 cl, 13 dwg, 43 ex

FIELD: medicine.

SUBSTANCE: inventions refer to the new inhibitors of hepatitis B virus replication, representing 1,1-dioxo-1,4-dihydro-2H-benzo[1,2,4]thiadiazin-3-ones of general formula 1, their pharmaceutically acceptable salts and/or hydrates. In general formula

wherein Ar1 and Ar2 represent phenyl optionally substituted by one, two or three identical or different substitutes specified in C1-C4alkyl, methoxyl, halogen, carboxyl and carbonitrile. The invention also refers to the pharmaceutical composition in the form of tablets, capsules or injections placed in a pharmaceutically acceptable pack and applicable for treating hepatitis B, and the method of preventing or treating hepatitis B.

EFFECT: higher efficacy of using the compounds.

6 cl, 1 tbl, 5 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes benzamidine derivatives of the general formula (I): wherein R1 means hydrogen atom, halogen atom, (C1-C6)-alkyl or hydroxyl; R2 means hydrogen atom or halogen atom; R3 means (C1-C6)-alkyl possibly substituted with hydroxy-group, alkoxycarbonyl-(C3-C13)-alkylsulfonyl, carboxy-(C2-C7)-alkylsulfonyl; each among R4 and R5 means hydrogen atom, halogen atom, (C1-C6)-alkyl possibly substituted with halogen atom, (C1-C6)-alkoxy-group, carboxy-group, (C2-C7)-alkoxycarbonyl, carbamoyl, mono-(C2-C7)-alkylcarbamoyl, di-(C3-C13)-alkylcarbamoyl; R6 means heterocycle or similar group; each among R7 and R8 means hydrogen atom, (C1-C6)-alkyl or similar group; n = 0, 1 or 2, or their pharmacologically acceptable salts, esters or amides. Compounds elicit the excellent inhibitory activity with respect to activated factor X in blood coagulation and useful for prophylaxis or treatment of diseases associated with blood coagulation.

EFFECT: improved method for prophylaxis and treatment, valuable medicinal properties of compound.

26 cl, 2 tbl, 253 ex

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: 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, pharmacy.

SUBSTANCE: invention relates to biologically active compounds, in particular, to substituted 5R1,6R2-thiadiazine-2-amines and pharmaceutical compositions comprising thereof that can be used in medicine as potential pharmacologically active substances eliciting the unique combination of properties: expressed anticoagulant activity in combination with capacity to inhibit aggregation of platelets. Effect of these substances differ from preparations used in medicinal practice and they can be used therefore in treatment of such diseases as myocardium infarction, disturbance in cerebral circulation, rejection of transplanted organs and tissues and so on. Indicated compounds correspond to the formula (I):

wherein values of radicals R1, R2 and R3 are given in the invention claim.

EFFECT: valuable medicinal properties of compounds.

4 cl, 2 tbl, 7 dwg, 33 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to applying compounds of the general formula (1):

as inhibitors of caspase-3 that allows their applying as "molecular tools" and as active medicinal substances inhibiting selectively the scheduling cellular death (apoptosis). Also, invention relates to pharmaceutical compositions based on compounds of the formula (1), to a method for their preparing and a method for treatment or prophylaxis of diseases associated with enhanced activation of apoptosis. Also, invention relates to new groups of compounds of the formula 91), in particular, to compounds of the formulae (1.1):

and (1.2):

. In indicated structural formulae R1 represents inert substitute; R2, R3 and R4 represent independently of one another hydrogen atom, fluorine atom (F), chlorine atom (Cl), bromine atom (Br), iodine atom (J). CF3, inert substitute, nitro-group (NO2), CN, COOH, optionally substituted sulfamoyl group, optionally substituted carbamide group, optionally substituted carboxy-(C1-C6)-alkyl group; R5 represents oxygen atom or carbon atom included in optionally condensed, optionally substituted and optionally comprising one or some heteroatoms; R6 represents hydrogen atom or inert substitute; X represents sulfur atom or oxygen atom.

EFFECT: improved preparing and applying methods, valuable medicinal and biochemical properties of compounds.

3 cl, 1 dwg, 2 tbl, 1 sch, 8 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes derivatives of 4-phenylpyridine N-oxides of the general formula (I) and their pharmaceutically acceptable acid-additive salts wherein R means hydrogen atom, lower alkyl or halogen atom; R1 means hydrogen atom; R2 and R2' mean independently of one another hydrogen, halogen atom, trifluoromethyl group, (lower)-alkoxy-group; or R2 and R2' can mean in common the group -CH=CH-CH=CH- optionally substituted with one or two substitutes taken among lower alkyl or (lower)-alkoxy-group; R3 and R3' mean independently of one another hydrogen atom, lower alkyl; R4 and R4' mean independently of one another -(CH2)mOR6 or lower alkyl; or R4 and R4' form in common with N-atom to which they are bound substituted R5-cyclic tertiary amine representing pyrrolidine-1-yl, piperidine-1-yl, piperazine-1-yl, morpholine-4-yl or 1,1-dioxomorpholine-4-yl; R5 means hydrogen atom, hydroxyl, -COOR3, -N(R3)CO-lower alkyl or -C(O)R3; R6 means hydrogen atom, lower alkyl; X means -C(O)N(R6)-, -N(R6)C(O)-; n = 0, 1, 2, 3 or 4; m = 1, 2 or 3. Also, invention describes a medicinal agent comprising these compounds. Compounds can be used as drugs in treatment or prophylaxis of diseases associated with antagonists of NK-1 receptor.

EFFECT: valuable medicinal properties of agent.

6 cl, 32 ex

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to new derivatives of 2-arylimino-2,3-dihydrothiazoles of the general formula (I): wherein radical values R1, R2, R3 and R4 are given in the claim invention. New compounds are useful in treatment of pathological states or diseases wherein one or some somatostatin receptors are implicated, for example, acromegaly, hypophysis adenomas or gastroenteropancreatic endocrine tumors with carcinoid syndrome and gastroenteric bleedings.

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

14 cl, 2825 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to derivatives of dihydronaphthalene represented by the formula (I):

wherein radical values are determined in the description and to its nontoxic salts. The proposed compound is a regulator of receptors activated by a peroxisome proliferator (PPAR) of α- and γ-type. The agent can be useful as a hypoglycemic agent, hypolipidemic agent, agent for prophylaxis and/or treatment of diseases associated with metabolic disturbances, agent increasing the content of HDL-cholesterol and reducing the content of LDL-cholesterol and/or VLDL-cholesterol and agent for weakening diabetes mellitus factor risk, and/or X-syndrome. Also, invention claims derivative of dihydronaphthalene representing 3-{5-{2-[2-(4-methylphenyl)-5-methyloxazol-4-yl]ethoxy}-3,4-dihydronaphthalen-1-yl}propanoic acid.

EFFECT: valuable medicinal properties of compounds and agent.

21 cl, 15 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula: or wherein x means 1, 2, 3 or 4; m means 1 or 2; n means 1 or 2; Q represents carbon atom (C) or nitrogen atom (N); A represents oxygen atom (O) or sulfur atom (S); R1 represents lower alkyl; X represents -CH; R2 represents hydrogen (H) or halogen atom; R2a, R2b and R2c can be similar or different and they are chosen from hydrogen atom (H), alkyl, alkoxy-group or halogen atom; R3 represents aryloxycarbonyl or alkoxyaryloxycarbonyl; Y represents -CO2R4 wherein R4 represents hydrogen atom (H) or alkyl, and including all their stereoisomers, their prodrugs as esters and their pharmaceutically acceptable salts. These compounds are useful antidiabetic and hypolipidemic agents and agents used against obesity also.

EFFECT: valuable medicinal properties of compounds.

29 cl, 12 tbl, 587 ex

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to derivatives of pyridazinone or triazinone represented by the following formula, their salts or their hydrates: wherein each among A1, A2 and A3 represents independently of one another phenyl group that can be optionally substituted with one or some groups chosen from the group including (1) hydroxy-group, (2) halogen atom, (3) nitrile group, (4) nitro-group, (5) (C1-C6)-alkyl group that can be substituted with at least one hydroxy-group, (6) (C1-C6)-alkoxy-group that can be substituted with at least one group chosen from the group including di-(C1-C6-alkyl)-alkylamino-group, hydroxy-group and pyridyl group, (7) (C1-C6)-alkylthio-group, (8) amino-group, (9) (C1-C6)-alkylsulfonyl group, (10) formyl group, (11) phenyl group, (12) trifluoromethylsulfonyloxy-group; pyridyl group that can be substituted with nitrile group or halogen atom or it can be N-oxidized; pyrimidyl group; pyrazinyl group; thienyl group; thiazolyl group; naphthyl group; benzodioxolyl group; Q represents oxygen atom (O); Z represents carbon atom (C) or nitrogen atom (N); each among X1, X2 and X3 represents independently of one another a simple bond or (C1-C6)-alkylene group optionally substituted with hydroxyl group; R1 represents hydrogen atom or (C1-C6)-alkyl group; R2 represents hydrogen atom; or R1 and R2 can be bound so that the group CR2-ZR1 forms a double carbon-carbon bond represented as C=C (under condition that when Z represents nitrogen atom (N) then R1 represents the unshared electron pair); R3 represents hydrogen atom or can be bound with any atom in A1 or A3 to form 5-6-membered heterocyclic ring comprising oxygen atom that is optionally substituted with hydroxyl group (under condition that (1) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; and each among A1, A2 and A3 represents phenyl group, (2) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o,p-dimethylphenyl group; A2 represents o-methylphenyl group, and A3 represents phenyl group, or (3) when Z represents nitrogen atom (N) then each among X1, X2 and X3 represents a simple bond; A1 represents o-methylphenyl group; A2 represents p-methoxyphenyl group, and A3 represents phenyl group, and at least one among R2 and R means the group distinct from hydrogen atom) with exception of some compounds determined in definite cases (1), (3)-(8), (10)-(16) and (19) given in claim 1 of the invention. Compounds of the formula (I) elicit inhibitory activity with respect to AMPA receptors and/or kainate receptors. Also, invention relates to a pharmaceutical composition used in treatment or prophylaxis of disease, such as epilepsy or demyelinization disease, such as cerebrospinal sclerosis wherein AMPA receptors take part, a method for treatment or prophylaxis of abovementioned diseases and using compound of the formula (I) for preparing a medicinal agent used in treatment or prophylaxis of abovementioned diseases.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

32 cl, 10 tbl, 129 ex

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