16-alkoxy-14-aryl-15-oxa-3,10-diazatetracyclo [8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetraene-2,11,12-triones and method for producing them

FIELD: chemistry.

SUBSTANCE: invention refers to a method for producing 16-alkoxy-14-aryl-15-oxa-3,10-diazatetracyclo-[8.7.0.01,13.04,9]heptadeca-4,6,8,13-tetraene-2,11,12-triones differing by the fact that 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones reacts with alkylvinyl esters in the inert aprotonic diluents medium that is followed by recovering end products.

EFFECT: developing the simple method for synthesis of 16-alkoxy-14-aryl-15-oxa-3,10-diazatetracyclo-[8,7,0,01,13,04,9]heptadeca-4,6,8,13-tetraene-2,11,12-triones.

2 cl, 1 tbl, 4 ex

 

The invention relates to the field of organic chemistry, namely to new individual compounds of the class 15-ox-3,10-diazatricyclo[8.7.0.01,13.04,9]heptadecane and to method of their production, which can be used as starting materials for the synthesis of new heterocyclic systems.

Known structural analogue of the claimed compounds - ethyl 4,5-dimethoxy-11,12-diokso-10-azotetrazole[8.7.0.01,13.02,7]heptadec-2,4,6,15-tetraen-13-carboxylate obtained by the interaction of ethyl 7,8-dimethoxy-2,3-diokso-4,5-dihydropyrrolo[2,1-a]isoquinoline-1-carboxylate with butadiene carried out by exposing the reactants in toluene at a temperature of 170°C for 30 hours (T. Sano, J. Toda, N. Kashiwaba et al., Heterocycles, 1981, v.l6, No. 7, p.1151-1156).

The disadvantages of this method include the inability to obtain the 16-alkoxy-14-aryl-15-ox-3,10-diazatricyclo[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-trions.

The object of the invention is to develop a simple method for the synthesis undescribed in the literature 16-alkoxy-14-aryl-15-ox-3,10-diazatricyclo[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-trions.

The task is carried out by boiling 3-koilpillai[1,2-a]quinoxaline-1,2,4(5H)-Trion (Ia-in) with alkylvinyl the esters in inert aprotic solvents on the trail�setup portion of the scheme:

I: Ar=Ph (a), (C6N4CL-4 (b), (C6H4OMe-4 (b);

II: Alk=Bu (a-b), Ar=Ph (a), (C6N4CL-4 (b), (C6H4OMe-4 (b).

The process is conducted at a temperature of 100°C and is used as a solvent of absolute 1,4-dioxane.

From the patent and technical literature were not identified ways of getting the 16-alkoxy-14-aryl-15-ox-3,10-diazatricyclo[8.7.0.01,13.04,9]-heptadec-4,6,8,13-tetraen-2,11,12-trions, sharing similar characteristics with the claimed method, namely not used starting materials, the solvent in which the reaction takes place, on what basis can you conclude that the claimed technical solution the criterion of "novelty" and "inventive step".

The invention is illustrated by the following examples.

Example 1. 14-Phenyl-16-ethoxy-15-ox-3,10-diazatricyclo-[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-Tryon (IIa).

To a solution of 3.0 mmol of 3-benzopyrrole[1,2-a]quinoxaline-1,2,4(5H)-Tryon (Ia) in 10 ml of absolute 1,4-dioxane was added a solution of 2.0 mmol of butylvinyl ether in 5 ml of absolute 1,4-dioxane was boiled for 1 hour, cooled, precipitated precipitate was filtered. A yield of 85%, a MP 241-242°C. (decomp., 1,4-dioxane). The compound (IIa) C24H22N2O5.

Found, %: C 68.78; H 5.34; N, 6.65.

Calculated, %: C 68.89; H 5.30; N, 6.69.

The compound (IIa) - yellow Chris�allicance substance soluble in DMSO and DMF, it is difficult soluble in the usual organic solvents, insoluble in water and Elkanah. Stable when stored under normal conditions.

In the IR spectrum of compound (IIa), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of NH group in the field 3193 cm-1, lactam carbonyl group With11=O in the region of 1730 cm-1, ketone groups (C12=O in the field 1694 cm-1and lactam carbonyl group With2=O in the region of 1680 cm-1.

In the PMR spectrum of the compound (IIa), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and related groups, there are singlet of NH group at 10.93 M. D., a multiplet of retinovoy group16N when 5.72 M. D., multiplet, methylene groups (C17H2at 2.30 M. D.

Example 2. 14-(4-Chlorophenyl)-16-ethoxy-15-dioxa-3,10-diazatricyclo-[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-Tryon (IIB).

To a solution of 3.0 mmol of 3-(4-chlorbenzoyl)imidazo[1,2-a]quinoxaline-1,2,4(5H)-Tryon (IB) in 10 ml of absolute 1,4-dioxane was added a solution of 2.0 mmol of butylvinyl ether in 5 ml of absolute 1,4-dioxane was boiled for 1.5 hours, cooled, precipitated precipitate was filtered. Yield 83%, t a MP 249-251°C.(decomp., 1,4-dioxane). The compound (IIB) C24H21ClN2O5.

Found, %: C 63.68; H 5.58; N, 6.11; Cl .88.

Calculated, %: C 63.65; H 4.67; N, 6.19; Cl, 7.83.

The compound (IIB) is a yellow crystalline substance, easily soluble in DMSO and DMF, it is difficult soluble in the usual organic solvents, insoluble in water and Elkanah. Stable when stored under normal conditions.

In the IR spectrum of compound (IIB), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of NH group in the field 3190 cm-1, lactam carbonyl group With11=O in the region of 1730 cm-1, ketone groups (C12=O in the area of 1698 cm-1and lactam carbonyl group (C2=O in the area of 1675 cm-1.

In the PMR spectrum of the compound (IIB), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and related groups, there are singlet of NH group at 10.94 M. D., a multiplet of retinovoy group16N when 5.72 M. D., a multiplet methylene group With17N2at 2.30 M. D.

Example 3. 14-(4-Methoxyphenyl)-16-ethoxy-15-ox-3,10-diazatricyclo[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-Tryon (IIB).

To a solution of 3.0 mmol of 3-(4-methoxybenzoyl)imidazo[1,2-a]quinoxaline-1,2,4(5H)-Tryon (IB) in 10 ml of absolute 1,4-dioxane was added a solution of 2.0 mmol of butylvinyl ether in 5 ml of absolute 1,4-dioxane was boiled for 50 min, cooled, precipitated precipitate was filtered. Yield 89%, t a MP 256-258°C.(decomp., 1,4 dioxane). The compound (IIB) C25H24N2O6.

Found, %: C 67.06; H 5.47; N, 6.35.

Calculated, %: C 66.95; H 5.39; N, 6.25.

The compound (IIB) is a yellow crystalline substance, easily soluble in DMSO and DMF, it is difficult soluble in the usual organic solvents, insoluble in water and Elkanah. Stable when stored under normal conditions.

In the IR spectrum of compound (IIB), filmed in the form of paste in vaseline oil, are the bands of stretching vibrations of NH group in the area of 3170 cm-1, lactam carbonyl group With11=O in the area of 1732 cm-1, ketone groups With12=O in the field 1699 cm-1and lactam carbonyl group With2=O in the area of 1677 cm-1.

In the PMR spectrum of the compound (IIB), filmed in a solution of DMSO-d6except for the signals of the protons of the aliphatic substituents, aromatic rings and related groups, there are singlet of NH group at 10.91 M. D., a multiplet of retinovoy group16N when 5.68 M. D., a multiplet methylene group With17N2at 2.28 M. D.

Example 4. Pharmacological study of the 16-alkoxy-14-aryl-15-ox-3,10-diazatricyclo[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-trions (IIa, b) in the presence of analgesic activity.

Analgesic activity link (IIa, b) relative to the dipyrone was determined by the method of thermal irritation of hot plasti�ka" by Eddie and Leimbach on outbred mice weighing 18-22 grams (N. B. Eddy, Leimbarh D. J. - Pharmacol & Exper. Gher. 1953., 385-393). Statistical processing of the experimental data was performed using t student test (M. L. Belenky, Elements of quantitative evaluation of the pharmacological effect. - 2nd ed. - L., 1963. - p. 152). The effect was considered significant at p<0,05.

Studies have shown (table), what compounds (IIa, b) possess analgesic activity. Data on pharmacological activity of analogues of the claimed compounds available in the literature.

Table
The analgesic activity of compounds (IIa, b)
No. connectionDose, mg/kgBeing defensive reflex via
2 hours2.5 hours
IIa50,/b19,40±2,38
IIb50,/b19,34±2,78
Control 2% of krahm. mucus50,/b8,95±0,78 10,75±1,63
Metamizole sodium93 (U50) [2]16,33±3,02

1. A method of producing a 16-alkoxy-14-aryl-15-ox-3,10-diazatricyclo-[8.7.0.01,13.04,9]heptadec-4,6,8,13-tetraen-2,11,12-trions, characterized in that 3-koilpillai[1,2-a]quinoxaline-1,2,4(5H)-Trion is subjected to interaction with alkylvinyl esters in an inert aprotic solvent, followed by separation of the target products.

2. A method according to claim 2, characterized in that the solvent used absolute 1,4-dioxane.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to improved method of obtaining pyridine compounds (AA),(BB) and (CC) of respective formulas:

,

,

.

said compounds possess inhibiting action with respect to HIV-integrase. method consists in carrying out the following stages: P-1) bromination of compound of formula (I-I) with obtaining bromine-compound of formula (II-II)

,

where value R represents -CHO, -CH(OH)2, -CH(OH)(OR4), -CH(OH)-CH2OH or -CH(OR5)(OR6); P1 represents benzyl; P3 represents H or protective group of carboxyl; R4 represents lower alkyl; R5 and R6 independently represent lower alkyl or R5 and R6 can represent alkyl and be connected with formation of 5-, 6- or 7-member ring, P-2) formation of side chain of 2,4-di-fluorophenyl-CH2-NH-C(O)- with application of reagents 2,4-di-fluorophenyl-CH2-NH2 and carbon monoxide, stage of formation of Q ring by means of respective amine, selected from 3-amino-butan-1-ol, 2-amino-propan-1-ol and 2-pyrrolidinyl methylamine, and stage of debenzylation with obtaining compound of formula (AA), (BB) or (CC), where said stage P-2 is carried out after formation of Q ring.

EFFECT: method makes it possible to simplify obtaining target compounds due to carrying out regioselective bromination at the first stage.

6 cl, 3 ex, 7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) where values of substituents are given in description, possessing inhibiting activity with respect to cathepsin K as well as to pharmaceutical compositions for treating diseases, associated with cysteine protease activity and to methods of inhibiting cathepsin K in mammals, requiring such treatment by introduction of efficient amount of compound to mammal.

EFFECT: claimed is application of formula (I) compound or its pharmaceutically acceptable salt in manufacturing medication for application in cathepsin K inhibition in a warm-blooded animal.

10 cl, 45 ex, 5 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel spirocyclic azaindole derivatives of formula I: , where: one of A stands for N, and the other ones stand for CR7-10; W stands for NR4; X stands for O, S; R1 and R2, independently on each other stand for H; C1-5-alkyl each time saturated, branched or unbranched, non-substituted or monosubstituted with -OC1-6alkyl; phenyl, thienyl, morpholinyl, benzothiophenyl or benzodioxilyl, each time non-substituted or monosubstituted with F, C1-6alkyl; or 5-membered heteroaryl, containing three nitrogen atoms as heteroatoms, substituted with C1-3alkyl; bound with C1-3-alkyl group phenyl non-substituted or monosubstituted with F or C1-6alkyl; R4 stands for H; R5 stands for H; R6 stands for H; R7, R8, R9 and R10 stand for H or CP3; in form of siastereomers, mixtures of diastereomers or separate diastereomer; bases and/or salts of physiologically compatible acids. Compounds are suitable for treatment of a number of diseases, for instance, pain, stress, depressions, etc. Described is method of their obtaining.

EFFECT: compounds are suitable for treatment of a number of diseases, for instance, pain, stress, depressions.

11 cl; 1 tbl; 34 ex

FIELD: chemistry.

SUBSTANCE: compounds, which have formula I , in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have values given in description and are inhibitors of receptor tyrosinkinases, useful in treatment of diseases, mediated by class 3 and class 5 receptor tyrosinkinases. It has been also discovered that specific compounds of the claimed invention are Pim-1 inhibitors. Also claimed is method of obtaining formula I compound.

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27 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds, specifically to 4-substituted-3-(1-alkyl-2-chloro-1H-indol-3-yl)furan-2,5-diones of general formula I , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R3=phenyl, naphthyl, 2-phenyl-1-ethenyl, thienyl, furyl, pyrrolyl, benzothiophenyl, benzofuranyl, indolyl, synthesis method thereof and use as compounds capable of photochemical generation of stable fluorophores of formula II, which can be used, for instance in information storage systems, particularly as photosensitive components of material for three-dimensional recording and storage of information. The invention also relates to novel 4,5-substituted-6-alkyl-1H-furo[3,4-c]carbazole-1,3(6H)diones of general formula II , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R4=H, R5=phenyl, R4, R5=benzo, naphtho, thieno, furo, pyrrolo, benzothieno, benzofuro, indolo, method for synthesis of said compounds and use as fluorophores.

EFFECT: obtaining novel compounds and possibility of using said compounds as fluorophores.

14 cl, 2 tbl, 8 ex

FIELD: medicine; pharmacology.

SUBSTANCE: new annelated asaheterocycles include pyrimidine fragment of general formula I in the form of free bases or pharmaceutically acceptable salts. Compounds of this invention possess properties of PI3 kinase inhibitors. In general formula I X represents oxygen atom or sulphur atom; Z represents oxygen atom, R1 represents hydrogen atom or optionally substituted C1-C6alkyl, or Z represents nitrogen atom together with bound carbon atom forming through Z and R1 optionally substituted annelated imidazoline cycle; R2 represents optionally substituted C1-C6alkyl, optionally substituted C3-C8cycloalkyl, optionally substituted phenyl, possibly annelated with 5-6-term heterocyclyl containing heteroatoms chosen from oxygen and nitrogen, optionally substituted 5-6-term heterocyclyl containing heteroatoms chosen from nitrogen, oxygen and/or sulphur, possibly annelated with phenyl ring. Invention also concerns method of production of compounds, pharmaceutical compositions and medical products.

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14 cl, 3 dwg, 1 tbl, 4 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel polycyclic compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7, cycle A, cycles B, X, Y and Z have values given in the invention claims and in description of the claim, and to their pharmaceutically acceptable salts also. Proposed compound possess an antitumor activity and can be used in treatment of oncological diseases. Also, invention relates to a pharmaceutical composition based on these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

23 cl, 1 tbl, 57 ex

FIELD: organic synthesis.

SUBSTANCE: invention relates to synthesis of camptotecin analogues from 2'-amino-5'-hydroxypropiophnone corresponding to AB ring portion of camptotecin structure and tricyclic ketone converted into CDE ring portion in camptotecin structure. Preparation of 2'-amino-5'-hydroxypropiophnone comprises following steps: (1) preparing compound (b) by mixing compound (a), benzylation agent, and a base followed by stirring mixture obtained in solvent on heating under reflux; (2) preparing compound (c) by dropwise adding Grignard reagent to compound (b) under an inert gas atmosphere; (3) preparing compound (d) by mixing compound (c) with an oxidant and stirring resulting mixture; and (4) preparing compound (e) via catalytic reduction of compound (d) (see scheme 1 below). Intermediate compounds (c') and (d') are described. Also described is a method for preparing tricyclic ketone to provide efficient complete synthesis of camptotecin serving as starting compound for irinotecan hydrochloride and a various types of camptotecin derivatives as well as for stable preparation of camptotecin and its derivatives. Scheme 1: .

EFFECT: expanded synthetic possibilities in camptotecin derivatives series.

5 cl, 17 tbl, 33 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to triheterocyclic compound of the formula (I): wherein X represents carbon atom; Y represents carbon or nitrogen atom; W represents carbon or nitrogen atom; U represents -CR2, and Z represents -CR2 or nitrogen atom; ring A represents (C5-C6)-cycloalkyl ring or 5-membered heterocyclic ring comprising one nitrogen, oxygen or sulfur atom; R1 represents alkyl, alkenyl, alkynyl, -NR4R5, -OR6 and others; R3 represents phenyl ring substituted with 1-3 substitutes or pyridyl or 1,3-dioxoindanyl ring substituted with 1-2 substitutes, and its pharmaceutically acceptable salts and pharmaceutical composition containing thereof as an active component. Also, invention relates to derivatives of pyrazolopyrimidine and derivatives of pyrrolopyrimidine. Compounds of the formula (I) show antagonistic activity with respect to corticotropin-releasing factor receptors. The compound can be used in treatment and/or prophylaxis of depression, anxiety state, disorders in food intake, post-traumatic stress, ulcerous disease, irritable bowel syndrome, Alzheimer's disease, abuse in drugs using or alcoholic syndrome dependence.

EFFECT: valuable medicinal properties of compounds and pharmaceutical agent.

7 cl, 1 dwg, 24 ex

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

SUBSTANCE: invention relates to new substituted pyrido[4',3':5,6]pyrano[2,3-d]pyrimidines of the general formula (1): or (2): or their pharmaceutically acceptable salts, N-oxides or hydrate possessing physiologically active properties, in particular, eliciting ability to induce apoptosis in tumor cells causing their death. In the general formula (1) or (2) X represents sulfur or oxygen atom; Y represents sulfur atom, group -SO, group -SO2, group -NH or group -NR6; R1 represents aryl, substituted aryl, heteroaryl; R2 and R5 represent hydrogen atom, alkyl, allyl, substituted benzyl, group -CH2-C(O)R3, group -CH2-C(O)NR3R4 wherein R3, R4 and R6 represent inert substitute. Also, invention relates to new combinatory libraries for search compound-leaders and candidates for medicinal compounds preparing by screening the combinatory libraries.

EFFECT: valuable medicinal properties of compounds.

9 cl, 1 tbl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a new substance eliciting an antiviral and antibacterial activity that is based on derivatives of 2,8-dithioxo-1H-pyrano[2,3-d;6,5-d']dipyrimidine and their 10-aza-analogues. This substance comprises derivative of indicated group of the general formula: A1*M: wherein X is taken among the group: oxygen atom (O), NH, N-alkyl; R1 is taken among the group: hydrogen atom (H), OH, chlorine atom (Cl), O-alkyl, NH2, NH-alkyl, NH-Ar, N-(alkyl)2, SH, S-alkyl; R2 is taken among the group: unsubstituted or substituted phenyl, naphthyl, thienyl; R3 is taken among the group: hydrogen atom (H), chlorine atom (Cl), O-alkyl, NH2, NH-alkyl, S-dihydroxypyrimidinyl; M is absent or taken among the group: cation Na, K, Li, ammonium or any other pharmacologically acceptable cation; or complex of pharmacologically acceptable cation (see above) with anion of one of derivatives of A1 (variants R1-R3 are given above). Invention provides preparing new compounds eliciting an antiviral and antibacterial activity.

EFFECT: valuable medicinal properties of substance.

17 cl, 7 tbl, 16 ex

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

SUBSTANCE: invention relates to new substituted pyrido[4',3':5,6]pyrano[2,3-d]pyrimidines of the general formula (1): or (2): or their pharmaceutically acceptable salts, N-oxides or hydrate possessing physiologically active properties, in particular, eliciting ability to induce apoptosis in tumor cells causing their death. In the general formula (1) or (2) X represents sulfur or oxygen atom; Y represents sulfur atom, group -SO, group -SO2, group -NH or group -NR6; R1 represents aryl, substituted aryl, heteroaryl; R2 and R5 represent hydrogen atom, alkyl, allyl, substituted benzyl, group -CH2-C(O)R3, group -CH2-C(O)NR3R4 wherein R3, R4 and R6 represent inert substitute. Also, invention relates to new combinatory libraries for search compound-leaders and candidates for medicinal compounds preparing by screening the combinatory libraries.

EFFECT: valuable medicinal properties of compounds.

9 cl, 1 tbl, 9 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to triheterocyclic compound of the formula (I): wherein X represents carbon atom; Y represents carbon or nitrogen atom; W represents carbon or nitrogen atom; U represents -CR2, and Z represents -CR2 or nitrogen atom; ring A represents (C5-C6)-cycloalkyl ring or 5-membered heterocyclic ring comprising one nitrogen, oxygen or sulfur atom; R1 represents alkyl, alkenyl, alkynyl, -NR4R5, -OR6 and others; R3 represents phenyl ring substituted with 1-3 substitutes or pyridyl or 1,3-dioxoindanyl ring substituted with 1-2 substitutes, and its pharmaceutically acceptable salts and pharmaceutical composition containing thereof as an active component. Also, invention relates to derivatives of pyrazolopyrimidine and derivatives of pyrrolopyrimidine. Compounds of the formula (I) show antagonistic activity with respect to corticotropin-releasing factor receptors. The compound can be used in treatment and/or prophylaxis of depression, anxiety state, disorders in food intake, post-traumatic stress, ulcerous disease, irritable bowel syndrome, Alzheimer's disease, abuse in drugs using or alcoholic syndrome dependence.

EFFECT: valuable medicinal properties of compounds and pharmaceutical agent.

7 cl, 1 dwg, 24 ex

FIELD: organic synthesis.

SUBSTANCE: invention relates to synthesis of camptotecin analogues from 2'-amino-5'-hydroxypropiophnone corresponding to AB ring portion of camptotecin structure and tricyclic ketone converted into CDE ring portion in camptotecin structure. Preparation of 2'-amino-5'-hydroxypropiophnone comprises following steps: (1) preparing compound (b) by mixing compound (a), benzylation agent, and a base followed by stirring mixture obtained in solvent on heating under reflux; (2) preparing compound (c) by dropwise adding Grignard reagent to compound (b) under an inert gas atmosphere; (3) preparing compound (d) by mixing compound (c) with an oxidant and stirring resulting mixture; and (4) preparing compound (e) via catalytic reduction of compound (d) (see scheme 1 below). Intermediate compounds (c') and (d') are described. Also described is a method for preparing tricyclic ketone to provide efficient complete synthesis of camptotecin serving as starting compound for irinotecan hydrochloride and a various types of camptotecin derivatives as well as for stable preparation of camptotecin and its derivatives. Scheme 1: .

EFFECT: expanded synthetic possibilities in camptotecin derivatives series.

5 cl, 17 tbl, 33 ex

FIELD: organic chemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel polycyclic compounds of the formula (I): wherein R1, R2, R3, R4, R5, R6, R7, cycle A, cycles B, X, Y and Z have values given in the invention claims and in description of the claim, and to their pharmaceutically acceptable salts also. Proposed compound possess an antitumor activity and can be used in treatment of oncological diseases. Also, invention relates to a pharmaceutical composition based on these compounds.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

23 cl, 1 tbl, 57 ex

FIELD: medicine; pharmacology.

SUBSTANCE: new annelated asaheterocycles include pyrimidine fragment of general formula I in the form of free bases or pharmaceutically acceptable salts. Compounds of this invention possess properties of PI3 kinase inhibitors. In general formula I X represents oxygen atom or sulphur atom; Z represents oxygen atom, R1 represents hydrogen atom or optionally substituted C1-C6alkyl, or Z represents nitrogen atom together with bound carbon atom forming through Z and R1 optionally substituted annelated imidazoline cycle; R2 represents optionally substituted C1-C6alkyl, optionally substituted C3-C8cycloalkyl, optionally substituted phenyl, possibly annelated with 5-6-term heterocyclyl containing heteroatoms chosen from oxygen and nitrogen, optionally substituted 5-6-term heterocyclyl containing heteroatoms chosen from nitrogen, oxygen and/or sulphur, possibly annelated with phenyl ring. Invention also concerns method of production of compounds, pharmaceutical compositions and medical products.

EFFECT: effective application for preparation of medical products for oncologic therapy.

14 cl, 3 dwg, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds, specifically to 4-substituted-3-(1-alkyl-2-chloro-1H-indol-3-yl)furan-2,5-diones of general formula I , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R3=phenyl, naphthyl, 2-phenyl-1-ethenyl, thienyl, furyl, pyrrolyl, benzothiophenyl, benzofuranyl, indolyl, synthesis method thereof and use as compounds capable of photochemical generation of stable fluorophores of formula II, which can be used, for instance in information storage systems, particularly as photosensitive components of material for three-dimensional recording and storage of information. The invention also relates to novel 4,5-substituted-6-alkyl-1H-furo[3,4-c]carbazole-1,3(6H)diones of general formula II , where R1=H, C1-C6 alkyl; R2=H, C1-C6 alkyl, C1-C6 alkoxy; R4=H, R5=phenyl, R4, R5=benzo, naphtho, thieno, furo, pyrrolo, benzothieno, benzofuro, indolo, method for synthesis of said compounds and use as fluorophores.

EFFECT: obtaining novel compounds and possibility of using said compounds as fluorophores.

14 cl, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: compounds, which have formula I , in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have values given in description and are inhibitors of receptor tyrosinkinases, useful in treatment of diseases, mediated by class 3 and class 5 receptor tyrosinkinases. It has been also discovered that specific compounds of the claimed invention are Pim-1 inhibitors. Also claimed is method of obtaining formula I compound.

EFFECT: increase of compound efficiency.

27 cl, 51 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel spirocyclic azaindole derivatives of formula I: , where: one of A stands for N, and the other ones stand for CR7-10; W stands for NR4; X stands for O, S; R1 and R2, independently on each other stand for H; C1-5-alkyl each time saturated, branched or unbranched, non-substituted or monosubstituted with -OC1-6alkyl; phenyl, thienyl, morpholinyl, benzothiophenyl or benzodioxilyl, each time non-substituted or monosubstituted with F, C1-6alkyl; or 5-membered heteroaryl, containing three nitrogen atoms as heteroatoms, substituted with C1-3alkyl; bound with C1-3-alkyl group phenyl non-substituted or monosubstituted with F or C1-6alkyl; R4 stands for H; R5 stands for H; R6 stands for H; R7, R8, R9 and R10 stand for H or CP3; in form of siastereomers, mixtures of diastereomers or separate diastereomer; bases and/or salts of physiologically compatible acids. Compounds are suitable for treatment of a number of diseases, for instance, pain, stress, depressions, etc. Described is method of their obtaining.

EFFECT: compounds are suitable for treatment of a number of diseases, for instance, pain, stress, depressions.

11 cl; 1 tbl; 34 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) where values of substituents are given in description, possessing inhibiting activity with respect to cathepsin K as well as to pharmaceutical compositions for treating diseases, associated with cysteine protease activity and to methods of inhibiting cathepsin K in mammals, requiring such treatment by introduction of efficient amount of compound to mammal.

EFFECT: claimed is application of formula (I) compound or its pharmaceutically acceptable salt in manufacturing medication for application in cathepsin K inhibition in a warm-blooded animal.

10 cl, 45 ex, 5 dwg

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