Method for production of pyrlindone hydrochloride

FIELD: organic chemistry.

SUBSTANCE: invention relates to improved synthesis method of pyrlindone hydrochloride having formula (I) 1. Method features intramolecular cyclization of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole hydrochloride of formula IV 2 at 80°-140°C with alkali agent in presence of phase transfer catalyst to provide 1,2,5,6-tetrahydro-8-methyl-pyrazine[3,2,1-j,k]-4H-carbazole of formula VI 3 followed by reduction at 80°-120°C. Method of present invention makes in possible to produce compound of formula I with yield nearly 70 % and purity more than 99 %.

EFFECT: method of high yield with reduced amount of alkali agent and phase transfer catalyst.

7 cl, 2 ex

 

The technical field

This invention relates to an improved process for the preparation of the hydrochloride pirlindola.

Prerequisites to the creation of inventions

Hydrochloride pirlindola (1,10-trimethylene-8-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole) of the formula (I)

it is antidepressant, which acts to return to normal norepinephrine, and as an inhibitor of MAO (monoamine oxidase) ("Drug of the future". Vol. V, No. 1, pp.39-41, 1980).

Describes various methods of synthesis of this molecule, and most of them are the source of 6-methyl-1,2,3,4-tetrahydrocarbazol-1-she of the formula (II)

For example, French patent 2132514 (in the name of the all-Russian research chemical-pharmaceutical Institute named after Sergo Ordzhonikidze) illustrates the way coming directly from the compounds of formula (II), which, when it is subjected to reaction with an alkaline agent, such as methoxide or ethoxide sodium, and then with chlorine-acetonitrile, gives 9-cyanomethyl-6-methyl-1,2,3,4-tetrahydrocarbazol-1-it, which by catalytic hydrogenation, preferably with Nickel Rennea or catalyst Adams (platinum oxide) and the subsequent deposition of alcoholic or ethereal solution chloroethanol acid leads to the desired product. Obviously, this method as according to claim what iciam security (chloro-acetonitrile is highly toxic; Nickel Renney is legalservices substance)and economic reasons (catalyst Adams is extremely expensive) is not easy to apply in an industrial scale.

Ivanov PU etc., Chem.-Pharm. J. (1987), 21(1), p.71-75 (hereafter "Ivanov et al.") describes the way in which do not have these disadvantages. He also comes from a 6-methyl-1,2,3,4-tetrahydrocarbazol-1-she of the formula (II), which, when it is subjected to reaction with ethanolamine, gives 6-methyl-1-(2-hydroxy-imino)-1,2,3,4-tetrahydrocarbazol formula (III)

His first transformed into a salt with a solution chloroethanol acid in ethanol, then treated with tionilhloridom to obtain the hydrochloride of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole formula (IV)

which when recovering the sodium borohydride gives the hydrochloride of 6-methyl-1-(2-chloroethyl-amino)-1,2,3,4-tetrahydrocarbazole formula (V)

This intermediate compound is subjected to reaction intramolecular cyclization to obtain the desired compound. The above cyclization is carried out using an alkaline agent in an aqueous solution, for example sodium hydroxide, in the presence of a catalyst transfer phases, using benzene as solvent for the reaction.

The alkaline agent IP is result in a large excess: in the example this article reported the use of a 50%aqueous solution, obtained on the basis of 15 g of sodium hydroxide (2.8 mol) in relation to 9,07 d derivative of formula (V) (30 mmol).

The same example gives the amount of the catalyst phase transfer 10 wt.% in relation to the same derivative of the formula (V).

The yield of the final product of this method is equal to 68.4% (based on the same intermediate compound of formula (IV).

Brief description of the invention

Now found a method for the synthesis of hydrochloride pirlindola, which not only represents an industrially applicable alternative to previously known methods, but also has advantages compared to the method proposed by Ivanov and others, in that it uses smaller amounts of reagents, still achieving the same output.

Detailed description of the invention

Therefore, this invention relates to a process for the synthesis of hydrochloride pirlindola formula (I)

characterized in that the hydrochloride of 6-methyl-1-(2-chloroethylamino)-1,2,3,4-tetrahydrocarbazole formula (IV)

cichlisuite, giving 1,2,5,6-tetrahydro-8-methyl-pyrazin[3,2,1-j,k]-4H-carbazol formula (VI)

which is subjected to recovery.

More specifically, this izobreteny which refers to the way which compound of formula (IV) cyclist by treatment with an alkaline agent in a molar ratio of from 1.5:1 to 3:1 in the presence of a catalyst phase transfer in the amount of 3 wt.%, receiving the compound of formula (VI), which is then restored with obtaining the compounds of formula (1).

The alkaline agent is a carbonate of an alkali metal such as sodium carbonate or potassium, preferably potassium carbonate.

Preferably the molar ratio between the alkaline agent and the compound of formula (IV) is 2.4:1,1.

The catalyst transfer phases selected from the group including tetrabutylammonium bromide and tetrabutylammonium phosphate. For purely practical reasons it is preferable application of tetrabutylammonium bromide.

The cyclization reaction occurs at a temperature between 80 and 140°C, preferably at 120°With, within a period of approximately 3 hours.

The reduction takes place at a temperature between 80 and 120°C, preferably at 100°With, within a period of approximately 5 hours.

The compound of formula (VI) may be restored with sodium borohydride.

The whole process of the invention is carried out in dimethylformamide, dimethylacetamide or simple monopetalum ether of ethylene glycol, and dimethylformamide is preferred.

The access method that is the subject of this invention, an equivalent is enten out of the way Ivanova and others, namely about 70% relative to the compound of formula (IV). The final product is obtained with a degree of purity higher than 99%.

As mentioned above, the method of the present invention provides the advantage concerning the use of very reduced quantities and alkaline agent and catalyst transfer phase reactions of intramolecular cyclization, reaching, however, the same yield of the final product. More specifically, the amount of catalyst transfer phase is more than twice less than the number used by Ivanov and others, while the amount of the alkaline agent, at least three times lower than in the specified method.

The fact of reducing the number of reagents is of benefit not only from an economic point of view, but also in relation to working conditions, which become more comfortable by reducing reaction volumes.

A further advantage of this method compared to method Ivanova and others is in fact the replacement of benzene, thinner, which is highly carcinogenic and therefore problematic to apply in addition to all in the pharmaceutical field compared with dimethylformamide or one of the other solvents listed above. The transition from benzene to dimethylformamide, dimethylacetamide or monomethylamine ether of ethylene glycol is not obser natim. Usually the most well-known alternative to benzene is toluene, as both solvent are vysokoparnymi, which is not the case with solvents that can be used in the method of this invention.

To better illustrate the invention, are given below in the following examples.

Example 1

Synthesis of 1,2,5,6-tetrahydro-8-methyl-pyrazin[3,2,1-j,k]-4H-carbazol

Hydrochloride 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole (29,7 g, 0.1 mol) dissolved in dimethylformamide (59,4 g), then add potassium carbonate (29,7 g, 0.21 mol) and tetrabutylammonium bromide (0.9 g). The reaction mixture is heated to 120-125°C for approximately 2 hours until, until there is no longer the original product (determined by TLC). The salt formed in the reaction mixture is separated by filtration and the resulting solution was used as is in the subsequent stage.

Example 2

Synthesis of hydrochloride pirlindola

To the solution obtained in example 1, add sodium borohydride (3.8 g, 0.1 mol) at 25-30°and allow the temperature to rise up to 90-100°C, then maintained at these values until, until there is no longer the original product. Adding chloroethanol acid crystals are formed, which is separated by filtration and cool. The obtained solid is subjected paracrystal the emission of a mixture of water/sec.-butanol, getting to 18.1 g specified in the title compound (yield calculated on the hydrochloride of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole: 69,1%). Purity >99.8% (IHVR).

1. The method of synthesis of the hydrochloride pirlindola formula (I)

using the hydrochloride of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole, characterized in that the hydrochloride of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole formula (IV)

cyclist at a temperature of 80-140°C with an alkaline agent in the presence of a catalyst transfer phases with getting 1,2,5,6-tetrahydro-8-methyl-pyrazin[3,2,1-j,k]-4H-carbazol formula (VI)

who are recovering at a temperature of 80-120°C.

2. The method according to claim 1, wherein the alkaline agent is present in a molar ratio of from 1.5:1 to 3:1 with the compound of the formula (IV), the catalyst transfer phase in an amount of 3 wt.%.

3. The method according to claim 2, in which the alkaline agent is an alkali carbonate selected from the group comprising potassium carbonate and sodium carbonate.

4. The method according to claim 2, in which the alkaline agent is used in a ratio of 2.4:1,1 with the compound of the formula (IV).

5. The method according to claim 1, in which the product of formula (VI) may be restored with sodium borohydride.

6. The method according to claim 1, which conducted the Yat in the solvent, selected from the group consisting of dimethylformamide, dimethylacetamide and nanometrology ether of ethylene glycol.

7. The method according to claim 6, in which the solvent is dimethylformamide.



 

Same patents:

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

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

20 cl, 6 tbl, 192 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

The invention relates to imidazole derivative of the formula (I)

or its pharmaceutically acceptable salt

The invention relates to organic chemistry and can find application in medicine

The invention relates to heterocyclic compounds with substituted phenyl group of formula Ior its pharmaceutically acceptable salt, in which R1represents a C1-C6alkyl; R2represents a C1-C6alkyl; R3represents H or halogen andrepresents a substituted heterocycle, as defined in paragraph 1 of the claims; and X represents NH or O

The invention relates to organic chemistry and can find application in medicine

The invention relates to an improved process for the preparation of 5-[2-ethoxy-5-(4-methylpiperazin-1-ylsulphonyl)-phenyl]-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazole[4,3-d]pyrimidine-7-she formulas (I) and its pharmaceutically acceptable salts by the interaction of the compounds of formula (II), where R1and R2means hydrogen or R1means hydrogen and R2means methyl, with a mixture of formic acid and formaldehyde in the presence of tetrabutylammonium bromide, and the ratio of tetrabutylammonium bromide to the original compound is from 1:60 to 1:130, preferably 1:100

The invention relates to organic chemistry and agriculture

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of benzodiazepine. Invention describes a derivative of benzodiazepine of the formula (I): wherein dotted lines show the possible presence of a double bond; R1, R2, R3, R4 and R5 are given in the invention claim; n represents 0, 1, 2, 3 or 4; X represents sulfur atom (S) or -NT wherein T is give in the invention claim; A represents hydrogen atom, (C6-C18)-aryl group substituted optionally with one or more substitutes Su (as given in the invention claim) or (C1-C12)-alkyl; or in alternative variant R4 and R5 form in common the group -CR6=CR7 wherein CR6 is bound with X and wherein R6 and R7 are given in the invention claim, and their pharmaceutically acceptable salts with acids or bases. It is implied that compounds corresponding to one of points (a)-(e) enumerated in the invention claim are excluded from the invention text. Also, invention describes methods for preparing compounds of the formula (I) and a pharmaceutical composition eliciting the hypolipidemic activity. Invention provides preparing new compounds eliciting the useful biological properties.

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

20 cl, 6 tbl, 192 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to a new derivative of bicyclic heteroaromatic compound of the general formula (I) or its pharmaceutically acceptable salt eliciting agonistic activity with respect to luteinizing hormone (LH). Compounds can be used for preparing medicinal agents for control ability for conception. In compounds of the general formula (I) R1 represents R7 wherein R7 represents (C6-C10)-aryl optionally substituted with halogen atom at ortho- and/or meta-position; NHR8, OR8 wherein R8 means (C1-C8)-alkyl that can be substituted with halogen atom, (C1-C8)-alkylcarbonyl, (C1-C8)-alkylcarbonyloxy-group, phenyl, (C6-C10)-arylcarbonylamino-group, 5-methyl-2-phenylimidazol-4-yl, (C6)-heterocycloalkyl wherein 1-2 heteroatoms are taken among nitrogen and oxygen atoms, ethyloxycarbonylmethylthio-(C1-C4)-alkoxy-group, amino-group, (C6-C7)-heteroaryl; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R2 represents (C1-C8)-alkyl or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; or (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; R3 represents (C1-C8)-alkyl possibly substituted with (C6-C14)-aryl possibly substituted with halogen atom, (C1-C4)-alkoxy-group, (C1-C4)-alkoxycarbonyl, mono- or tri-(C6-C10)-cycloalkyl, (C6-C10)-aryl, (C5-C6)-heteroaryl comprising nitrogen, oxygen or sulfur atom as a heteroatom; (C5-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; (C3-C8)-cycloalkyl, (C2-C7)-heterocycloalkyl comprising 2 heteroatoms taking among nitrogen or oxygen atom; or (C6-C10)-aryl optionally substituted with one or more substitutes taken among (C1-C8)-alkoxy-group; X represents sulfur atom (S) or N(R4); Y represents nitrogen atom (N); R4 represents (C1-C8)-alkyl, phenyl-(C1-C8)-alkyl; or X represents sulfur atom (S), and Y represents CH; Z represents NH2 or OH; A represents sulfur (S), oxygen atom (O) or a bond. Also, invention relates to a pharmaceutical composition.

EFFECT: valuable properties of compounds and composition.

14 cl, 1 tbl, 119 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to improved synthesis method of pyrlindone hydrochloride having formula (I) 1. Method features intramolecular cyclization of 6-methyl-1-(2-chloroethyl-imino)-1,2,3,4-tetrahydrocarbazole hydrochloride of formula IV 2 at 80°-140°C with alkali agent in presence of phase transfer catalyst to provide 1,2,5,6-tetrahydro-8-methyl-pyrazine[3,2,1-j,k]-4H-carbazole of formula VI 3 followed by reduction at 80°-120°C. Method of present invention makes in possible to produce compound of formula I with yield nearly 70 % and purity more than 99 %.

EFFECT: method of high yield with reduced amount of alkali agent and phase transfer catalyst.

7 cl, 2 ex

FIELD: organic chemistry, pharmaceutical compositions.

SUBSTANCE: invention relates to novel pyrasolbenzodiazepines of formula I 1 (in formula R1 is hydrogen, -NO2, -CN, halogen, -OR5, -COOR7, -CONR8R9, -NR10R11, NHCOR12, NHSO2R13; each R2 and R4 independently of one another are hydrogen, halogen, -NO2, -CF3; R3 is hydpegen, C3-C8-cycloalkyl, aryl, in particular C6-C10-aromatic group having 1 or 2 rings, 5-10-membered heteroaryl, having 1 or 2 rings and1-3 heteroatoms, selected from N, O, and S, -COOR7, CN, C2-C6-alkenyl, -CONR8R9 or C1-C6-alkyl optionally substituted with OR9-group, F or aryl as mentioned above; R5 is C1-C6-alkyl; R7 is hydrogen or C1-C6-alkyl; each independently of one another are hydrogen or C1-C6-alkyl optionally substituted with hydroxyl or NH2, or alternatively R8 and R9 together form morpholino group; each R10,R11 and R12 independently of one another are hydrogen or C1-C6-alkyl; R13 is C1-C6-alkyl optionally substituted with halogen or -NR14R15; each R14 and R15 independently of one another are hydrogen or C1-C6-alkyl optionally substituted with halogen; or alternatively -NR14R15 is morpholino group) or pharmaceutically acceptable salts thereof, as well as to certain pyrasolbenzodiazepine derivatives, thiolactam intermediates for production of compound (I) and pharmaceutical compositions containing the same. Compound and pharmaceutical composition of present invention are cycline-dependent kinase (CDK2) inhibitors and antiproliferation agents used in treatment or controlling disorders associated with cell proliferation, in particular breast, colon, lung and/or prostate tumors.

EFFECT: new antiproliferation agents.

20 cl, 12 tbl, 8 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: compounds satisfying the formula I 1 are disclosed, wherein each R1 and R2 independently to one another are H, OH, OA or Hal; or R1 and R2 together are -O-CH2-O- or -O-CH2-CH2-O-; R3 and R4 are A-group; X - group monosubstituted with R8, R5 or R7; R5 is linear or branched C1-C10-alkylene, wherein one or two CH2-groups may be substituted with oxygen atom; R7 is phenyl or phenylmethyl; R8 is COOH, COOA, CONH2, CONHA, CON(A)2 or CN; F is C1-C6-alkyl; and Hal is F, Cl, Br, or I, as well as physiologically acceptable salts or solvates thereof. Methods for production of claimed compounds (I) and pharmaceutical composition containing the same also are disclosed. Said compounds and pharmaceutical composition have activity as phosphodiesterase V inhibitors and are useful in treatment of cardiovascular diseases and potency disorders.

EFFECT: pharmaceutically applicable compounds and compositions.

7 cl, 16 ex

FIELD: organic chemistry, medicine, gastroenterology, pharmacy.

SUBSTANCE: invention relates to a pyrrolopyridazine derivative of the following formula: wherein R1 represents (C3-C7)-cycloalkyl-(C1-C6)-alkyl group that can be substituted optionally with (C1-C6)-alkyl group; R2 represents (C1-C6)-alkyl group; R3 represents hydroxymethyl group, (C2-C6)-aliphatic acyloxymethyl group, (C6-C10)-arylcarbonyloxymethyl group, (C1-C6)-alkoxycarbonyloxymethyl group, formyl group, carboxyl group, (C1-C6)-alkoxycarbonyl group or (C6-C10)-aryloxycarbonyl group; R4 represents (C6-C10)-aryl group that can be substituted optionally with substitutes taken among the group consisting of (C1-C6)-alkyl groups, halogen-(C1-C6)-alkyl groups, (C1-C6)-alkoxy-groups, halogen-(C1-C6)-alkoxy-groups and halogen atoms; A represents imino-group, oxygen or sulfur atom, or its pharmaceutically acceptable salt. Pyrrolopyridazine derivatives elicit inhibitory activity with respect to gastric juice secretion and protective activity with respect to stomach mucosa and can be useful as a curative agent for prophylaxis or treatment of ulcer disease. Except for, invention relates to a pharmaceutical composition based on compounds of the invention and to a method for prophylaxis and treatment of ulcer disease.

EFFECT: valuable medicinal properties of compound.

25 cl, 1 tbl, 11 ex

FIELD: organic chemistry of heterocyclic compounds, medicine, pharmacy.

SUBSTANCE: invention describes bicyclical nitrogen-containing heterocycles of the general formula (I): , wherein R1 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, pyridyl, naphthyl, furyl-(C1-C4)-alkyl, phenyl optionally substituted with di-(C1-C7)-alkylamino-(C1-C7)-group, halogen atom, (C1-C7)-alkoxy-group or hydroxy-(C1-C7)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group, amino-(C1-C7)-alkyl, amino-group or di-(C1-C7)-alkylamino-(C1-C7)-alkoxy-group; R2 means (C1-C7)-alkyl, (C3-C7)-cycloalkyl, furyl-(C1-C4)-alkyl, pyridyl or its N-oxide; phenyl optionally substituted with halogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, hydroxy-group or trifluoromethyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxy-group; R3 means hydrogen atom, (C1-C7)-alkyl, (C3-C7)-cycloalkyl-(C1-C4)-alkyl, (C3-C7)-cycloalkenyl, pyridyl-(C1-C4)-alkyl, naphthyl, phenyl optionally substituted with phthalimido-(C1-C4)-alkyl, amino-(C1-C7)-alkyl, hydroxy-(C1-C7)-alkyl, (C1-C7)-alkylamino-(C1-C7)-alkyl, di-(C1-C7)-alkylamino-(C1-C7)-alkyl, morpholino-(C1-C4)-alkyl or piperazinyl-(C1-C4)-alkyl, or phenyl-(C1-C7)-alkyl optionally substituted with (C1-C7)-alkoxycarbonyl or carboxy-group. Also, invention relates to pharmaceutically acceptable salts of compounds of the formula (I) as a base with acids or pharmaceutically acceptable salts of compounds of the formula (I) as acid with bases, and pharmaceutical composition based on thereof. Compounds described above show inhibitory activity with respect to tyrosine kinase and can be used in treatment or prophylaxis of inflammatory, immunological, oncological, bronchopulmonary, dermatological and cardiovascular diseases, for treatment of asthma, disorders in the central nervous system or complications associated with diabetes mellitus, or for prophylaxis against transplant rejection after surgery transplantation.

EFFECT: valuable medicinal properties of compounds and composition.

14 cl, 1 tbl, 92 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new azaheterocycles comprising fragment of piperidin-2-yl- of the general formula (1):

as separate enantiomers or mixture of enantiomers, or their pharmaceutically acceptable salts, oxides or hydrates. In compounds of the formula (1) R1 represents hydrogen atom, inert substitute or NH-protecting substitute; W represents optionally substituted azaheterocycle, such as: pyridin-3-yl, pyrazolo[1,5-a]pyridin-6-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-7-yl, 3,4-dihydro-2H-pyrido[1,2-a]pyrimidin-9-yl, imidazo[1,2-a]pyrimidin-6-yl, imidazo[1,2-a]pyrimidin-8-yl or [1,8]naphthyridin-3-yl. Compounds elicit activity with respect to nicotine receptors and can be used in pharmaceutical industry. Also, invention relates to the focused library for search of physiologically active compound-leaders, and to pharmaceutical compositions based on new compounds of the formula (1).

EFFECT: valuable medicinal and pharmacological properties of compounds.

9 cl, 1 tbl, 15 sch, 22 ex

FIELD: organic chemistry, medicine, pharmacy.

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

wherein A represents bicyclic or tricyclic azepine derivative; V1 and V2 both represent hydrogen atom (H) or one among V1 and V2 represents hydrogen atom (H), OMe, OBn, OPh, O-acyl, Br, Cl, F, N3, NH2, NHBn and another represents hydrogen atom (H); or V1 and V2 represent in common =O or -O(CH2)pO-; W1 represents oxygen (O) or sulfur (S) atom; X1 and X2 both represent hydrogen atom (H) or in common represent =O or =S; Y represents OR5 or NR6R7; R1 means hydrogen atom (H), lower alkyl, F, Cl and Br; R2 means lower alkoxy-group or values given for R1; R3 and R5 are taken independently among hydrogen atom (H) and lower alkyl; R4 means hydrogen atom (H); R6 and R7 are taken independently among hydrogen atom (H) and lower alkyl, or they in common mean -(CH2)n-; n = 3, 4, 5 or 6; p = 2 or 3. These compounds are agonists of vasopressin V2 receptors and useful as antidiuretic and procoagulants, and also to pharmaceutical compositions comprising these vasopressin agonists. These compositions are useful especially in treatment of diabetes insipidus of the central origin and night enuresis.

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

26 cl, 1 tbl, 119 ex

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