Tetrahydroimidazo[1,5-a]pyrazine derivatives, method for preparing and using them in medicine

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to tetrahydroimidazo[1,5-a]pyrazine derivatives of formula I or to their pharmaceutically acceptable salts (I), wherein: Ar represents phenyl, wherein phenyl is additionally substituted by 1-3 substitutes independently specified in halogen; R1 represents trifluoromethyl; R2 is specified in a group consisting of hydrohyl, alkyl having 1 to 4 carbon atoms, alkoxyl having having 1 to 4 carbon atoms, cycloalkyl representing a 5-6-member monocyclic ring group consisting of carbon completely, and -NR4R5, wherein each alkoxyl is optionally substituted by one group specified in a group consisting of phenyl and -OC(O)OR8; R3 is specified in a group consisting of a hydrogen atom and alkyl having 1 to 4 carbon atoms; each of R4 and R5 is independently specified is a group consisting of a hydrogen atom, alkyl having 1 to 4 carbon atoms, cycloalkyl representing a 3-8-member monocyclic ring group consisting of carbon completely, phenyl and pyridinyl, wherein each alkyl or phenyl is optionally substituted by one or more group specified in a group consisting of halogen, a cyano group, -SO2R7, -NR4R5 and -C(=O)OCH3; or R4 and R5 together with an atom, whereto attached form a 5-6-member heterocycle wherein the 5-6-member heterocycle optionally contains one or more N, O or S atom, and each 5-6-member heterocycle is optionally substituted by one or more groups consisting of halogen, hydroxyl, an amino group, alkyl having 1 to 4 carbon atoms, hydroxyalkyl 1 to 4 carbon atoms, -SO2R7, -C(O)NR4R5, -C(O)R7, =O; R7 represents alkyl 1 to 4 carbon atoms; and R8 is specified in a group consisting of alkyl 1 to 4 carbon atoms, and cycloalkyl representing a 5-6-member monocyclic ring group consisting of carbon completely. The invention also refers to methods for preparing them, a pharmaceutical composition having dipeptidyl peptidase IV inhibitory activity and containing said derivatives.

EFFECT: there are produced new compounds and composition on their basis which can find application in medicine for treating type 2 diabetes mellitus or hyperglycemia.

17 cl

 

The text descriptions are given in facsimile form.

1. Compounds having the formula (I)or their pharmaceutically acceptable salts:

where Ar represents phenyl, where phenyl is additionally substituted by 1-3 substituents, independently selected from halogen;
R1represents trifluoromethyl;
R2selected from the group consisting of hydroxyl, alkyl having from 1 to 4 carbon atoms, alkoxyl having from 1 to 4 carbon atoms, cycloalkyl, which represents a 5-6-membered consisting entirely of carbon monocyclic ring group, and-NR4R5where each alkoxy possibly substituted by one group selected from the group consisting of phenyl and
-OC(O)OR8;
R3selected from the group consisting of hydrogen atom and alkyl having about the 1 to 4 carbon atoms;
each of R4and R5independently selected from the group consisting of hydrogen atom, alkyl having from 1 to 4 carbon atoms, cycloalkyl representing a 3-8-membered consisting entirely of carbon monocyclic ring group, phenyl and pyridinyl, where the alkyl or phenyl, each possibly substituted by one or more than one group selected from the group consisting of halogen, ceanography, -SO2R7, -NR4R5and-C(=O)OCH3;
or R4and R5together with the atom to which they are attached, form a 5-6-membered heterocycle, where 5-6-membered heterocycle optionally contains one or more than one atom of N, O or S, and each 5-6-membered heterocycle possibly substituted by one or two groups selected from the group consisting of halogen, hydroxyl, amino, alkyl having from 1 to 4 carbon atoms, hydroxyalkyl having from 1 to 4 carbon atoms, -SO2R7, -C(O)NR4R5, -C(O)R7, =O;
R7represents alkyl having from 1 to 4 carbon atoms; and
R8selected from the group consisting of alkyl having from 1 to 4 carbon atoms, and cycloalkyl, which represents a 5-6-membered consisting entirely of carbon monocyclic ring group.

2. Compounds or their pharmaceutically acceptable salts according to claim 1, where the compound is selected from the group consisting of:














and.

3. Compounds or their pharmaceutically acceptable salts for the .1, where compounds selected from the group consisting of:














and.

4. Connect the indicators or their pharmaceutically acceptable salts according to claim 1 or 2, where salts are salts formed by the compounds and acids selected from the group consisting of hydrochloric acid, phosphoric acid and triperoxonane acid, preferably the salt is a hydrochloride.

5. Compounds having the formula (IA), as intermediates in the synthesis of compounds according to claim 1, having the formula (I):

where Ar represents phenyl, where phenyl is additionally substituted by 1-3 substituents, independently selected from halogen;
R1represents trifluoromethyl;
R3selected from the group consisting of hydrogen atom and alkyl having from 1 to 4 carbon atoms; and
X represents halogen.

6. Compounds having the formula (IB), as intermediates in the synthesis of compounds according to claim 1, having the formula (I),

where R1represents trifluoromethyl;
R2selected from the group consisting of hydroxyl, alkyl having from 1 to 4 carbon atoms, alkoxyl having from 1 to 4 carbon atoms, cycloalkyl, which represents a 5-6-membered consisting entirely of carbon monocyclic ring group, and-NR4R5where each alkoxy possibly substituted by one group selected from the group consisting of phenyl and -- OC(O)OR8;
R3selected from a group is s, consisting of hydrogen atom and alkyl having from 1 to 4 carbon atoms;
each of R4and R5independently selected from the group consisting of hydrogen atom, alkyl having from 1 to 4 carbon atoms, cycloalkyl representing a 3-8-membered consisting entirely of carbon monocyclic ring group, phenyl and pyridinyl, where each alkyl or phenyl possibly substituted by one or more than one group selected from the group consisting of halogen, ceanography, -SO2R7, -NR4R5and-C(=O)och3;
or R4and R5together with the atom to which they are attached, form a 5-6-membered heterocycle, where 5-6-membered heterocycle optionally contains one or more than one atom of N, O or S, and each 5-6-membered heterocycle possibly substituted by one or two groups selected from the group consisting of halogen, hydroxyl, amino, alkyl having from 1 to 4 carbon atoms, hydroxyalkyl having from 1 to 4 carbon atoms, -SO2R7, -C(O)NR4R5, -C(O)R7, =O;
R7represents alkyl having from 1 to 4 carbon atoms; and
R8selected from the group consisting of alkyl having from 1 to 4 carbon atoms, and cycloalkyl, which represents a 5-6-membered consisting entirely of carbon monocyclic ring group.

7. The way the floor is possible compounds according to claim 5, having the formula (IA)comprising the following stages:

carrying out the reaction of the acid anhydride with pyrazin-2-methylamine (IA_1) to obtain the amide (IA_2),

condensation of amide (IA_2) to obtain the derived imidazole[1,5-α]pyrazine (IA_3);

restore derived imidazole[1,5-α]pyrazine (IA_3) to give the substituted R1and R3derived tetrahydroimidazo[1,5-α] pyrazine (IA_4);

carrying out the reaction of substituted R1and R3derived tetrahydroimidazo[1,5-α]pyrazine (IA_4) with carboxylic acid (IA_5) in the presence of a condensation reagent to obtain condensation products of (IA_6),

halogenoalkane condensation products of (IA_6) to obtain the compounds of formula (IA); where Ar, R1, R3and X are such as defined in claim 5.

8. Method of preparing compounds according to claim 6 having the formula (IB), comprising the following stages:

recovery substituted R1derived imidazole[1,5-α]pyrazine (IB-1) and the protection of the amino group resulting from the recovered product with obtaining protected on the amino group, substituted R1derived imidazole[1,5-α]pyrazine (IB-2),

halogenide is the use of protected amino group, substituted R1derived imidazole[1,5-α]pyrazine (IB-2) with a halogenated compound (IB-3);

transformation of halogenated compounds (IB-3) in the substituted ether derived tetrahydroimidazo[1,5-α]pyrazine (IB-4);

hydrolysis of substituted ether derived tetrahydroimidazo[1,5-α]pyrazine (IB-4) to obtain the compound of carboxylic acid (IB-5);

the conversion of compounds of carboxylic acid (IB-5) to obtain compound (IB-6),

the conversion of compound (IB-6) to obtain the substituted ketone derived tetrahydroimidazo[1,5-α]pyrazine (IB-7),

remove protection substituted with a ketone derivative of tetrahydroimidazo[1,5-α]pyrazine (IB-7) to obtain the compounds of formula (IB)where R1, R2and R3are as defined in claim 6, X is a halogen.

9. Method of preparing compounds according to claim 1 to 3, having the formula (I), comprising the following stages:

the interaction of the compounds of formula (IA) according to claim 5 with octacarbonyl of dicobalt and CHLOROACETATE in the solvent methanol in the oil bath in an atmosphere of carbon monoxide and subsequent hydrolysis of the resulting product in the presence of the basis of the Oia at room temperature and acidification with obtaining carboxylic acid (IA_7);

the interaction of the resulting carboxylic acid (IA_7) with an amine, where the specified amine is a other4R5in the presence of a condensation reagent at room temperature, with the subsequent removal of the protection of the amino group in the presence of acid to obtain the compounds of formula (I),
where Ar, R1, R2, R3, R4and R5are as defined in claim 1, X represents a halogen.

10. Method of preparing compounds according to claim 1 to 3, having the formula (I), comprising the following stages:

the interaction of the compounds of formula (IA) according to claim 5 with octacarbonyl of dicobalt and CHLOROACETATE in the solvent methanol in the oil bath in an atmosphere of carbon monoxide and subsequent hydrolysis of the resulting product in the presence of a base at room temperature and acidification with obtaining carboxylic acid (IA_7);

the interaction of the resulting carboxylic acid (IA_7) with alcohol selected from the group consisting of ethanol, benzyl alcohol, isopropanol and tertbutanol, in the presence of a condensation reagent at room temperature, with the subsequent removal of the protection of the amino group in the presence of acid to obtain the compounds of formula (I),
where Ar, R1, R2and R3are the hat, as defined in claim 1, X represents a halogen.

11. Method of preparing compounds according to claims 1 to 3, having the formula (I), comprising the following stages:

the interaction of the compounds of formula (IA) according to claim 5 with octacarbonyl of dicobalt and CHLOROACETATE in the solvent methanol in the oil bath in an atmosphere of carbon monoxide and subsequent hydrolysis of the resulting product in the presence of a base at room temperature and acidification with obtaining carboxylic acid (IA_7);

the interaction of the resulting carboxylic acid (IA_7) with 1-halogenated carbonate selected from the group consisting of 1-chloramination, 1-chlorotriisopropylsilane and 1-chlorotestosterone, with the subsequent removal of the protection of the amino group in the presence of acid to obtain the compounds of formula (I),
where Ar, R1, R2and R3are as defined in claim 1, X represents a halogen.

12. Method of preparing compounds according to claims 1 to 3, having the formula (I), comprising the following stages:

the interaction of the compounds of formula (IB) according to claim 6 with a carboxylic acid in the presence of a condensation reagent bis(2-oxo-3-oxazolidinyl)phosphonium chloride with obtaining the product of condensation and subsequently removing the protection of the amino group with the floor is in the compounds of formula (I),
where Ar, R1, R2and R3are as defined in claim 1.

13. The method of receiving according to claim 9 or 12, also comprising a stage of the reaction the resulting compounds having the formula (I)with acids to produce salts accession acid, where the acid is selected from the group consisting of hydrochloric acid, phosphoric acid and triperoxonane acid, where preferably the salt is a salt of hydrochloric acid.

14. The pharmaceutical composition having inhibitory activity against dipeptidylpeptidase IV containing the compound or its salt according to any one of claims 1 to 4 in a therapeutically effective dose, as well as pharmaceutically acceptable carrier or excipient.

15. The use of the compounds or their pharmaceutically acceptable salts according to any one of claims 1 to 4 for the manufacture of a medicinal product for the treatment of type 2 diabetes or hyperglycemia.

16. A method of inhibiting the catalytic activity of dipeptidylpeptidase IV, characterized by the fact that dipeptidyl peptidase IV is brought into contact with the compounds or their pharmaceutically acceptable salts according to any one of claims 1 to 4.

17. The use of the pharmaceutical composition according to 14 for the manufacture of a medicinal product for the treatment of type 2 diabetes or hyperglycemia.



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel azoindolizines or pharmaceutically acceptable salts thereof having Mek-kinase inhibitory activity in formula : ZA means CRA; RA means H or halogen; each of R1, R2 and R3 means H; W means: , each R4 and R5 means H; X1 represents -OR7; each R7 means C2-C12-hydroxyalkyl, 2,3-dihydroxypropyl, C2-C3-alkenoxyC1-C6-alkoxy, (2,2-dimethyl-[1,3]dioxalan-4-yl)-methyl or piperidinyl; X4 means: R6 means halogen or -SR16; R6 means halogen; p is equal to 1; R16 means C1-C12-alkyl.

EFFECT: invention relates to a pharmaceutical compositions containing these compounds, to a method of inhibiting the abnormal cell growth and the use of the compounds for preparing a drug preparation for inhibiting the abnormal cell growth.

9 cl, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel quinoline compounds of formula (I) and physiologically acceptable acid addition salts and N oxides thereof, wherein R denotes a polycyclic group of formula (R) wherein * indicates the quinolinyl radical binding site; A denotes (CH2)a, where a equals 0, 1, 2 or 3; B denotes (CH2)b, where b equals 0, 1, 2 or 3; X' denotes (CH2)x where x equals 0, 1, 2 or 3; Y denotes (CH2)y where y equals 0, 1, 2 or 3; provided that a+b=1, 2, 3 or 4, x+y=1, 2, 3 or 4, and a+b+x+y=3, 4, 5, 6 or 7; Q denotes N; R1 denotes hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, phenyl-C1-C4-alkyl, C1-C4-alkylcarbonyl, C1-C4-alkoxycarbonyl, phenoxycarbonyl or benzyloxycarbonyl, where phenyl rings in last two said groups are unsubstituted or carry 1, 2 or 3 substitutes selected from halogen, C1-C4-alkyl or C1-C4-halogenalkyl; R2 denotes hydrogen; R3 denotes hydrogen; p=0, 1 or 2; R4, if present, denotes C1-C4-alkyl and is bonded with X and/or Y, if p=2, two radicals R4, which are bonded with adjacent carbon atoms of X or Y, together can also denote a straight C2-C5-alkylene; q=0; n=0; m=0; X denotes S(O)2; which is located in position 3 of quinoline; Ar denotes a radical Ar1, wherein Ar1 is a phenyl, wherein the phenyl can be unsubstituted or can carry 1 substitute Rx wherein Rx denotes halogen, CN, C1-C6-alkyl, C1-C6-halogenalkyl, C1-C6-alkoxy, C1-C6-halogenalkoxy, C1-C6-alkylthio, C1-C6-halogenalkylthio, NRx1 Rx2, wherein Rx1 and Rx2 independently denote hydrogen, C1-C6-alkyl, or Rx1 and Rx2 together with a nitrogen atom form an N-bonded 5-, 6- or 7-member saturated heteromonocyclic ring or an N-boned 7-, 8-, 9- or 10-member saturated heterobicyclic ring, which are unsubstituted or carry 1, 2, 3 or 4 radicals selected from C1-C4-alkyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treatment using the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel quinoline derivatives are obtained, which respond to modulation of the serotonin 5-HT6 receptor.

23 cl, 2 tbl, 44 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new tetracyclic compounds of general formula (I), wherein is a single or double bond; no bonds or a single bond; or V means N; T and X as shown in structure fragments above; U and W independently mean C or N with one of them shall be N; R3, R4, R5 and R6 - H; Rv is absent; Ru and Rw are independently absent or mean (C1-12)alkyl; Y =N-OR1 or NP'1, wherein R1 - H, (C1-12)alkyl optionally substituted by phenyl, phenyloxy, carboxy, (C1-12)alkoxy, (C1-12)alkoxycarbonyl, or (C2-12)alkenyl; R'1 is phenyl, or pharmaceutically acceptable salts thereof, or diastereomers thereof, or regioisomers thereof, or: mixtures thereof, a pharmaceutical composition containing them, and specific compounds for cysteine protease inhibition.

EFFECT: compounds may be used in medicine in treating cancer, neurodegenerative diseases, inflammatory disorders, cardiovascular diseases, etc.

8 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new pyrimidine substituted macrocyclic compounds of genral formula (I) , wherein A= -C(=O)OR1 or -C(=O)-NH-SO2-R2; R1 = H or C1-6alkyl; R2 = phenyl, thienyl, C3-7cycloalkyl optionally substituted by C1-6alkyl; X = N or CH; E = NR5; R5 = H or C1-6alkyl; n = 4 or 5; R7=H, C1-6alkyl, C1-6alkoxy, phenyl optionally substituted by C1-6alkoxy; R8 =C1-6alkoxy, phenyl optionally substituted by C1-6alkoxy, morpholino or -NRaRb, wherein Ra and Rb independently mean H or C1-6alkyl; R9 = Rq = H; or their pharmaceutically acceptable addition salts, or stereoisomers, and pharmaceutical compositions containing them.

EFFECT: compounds are inhibitors of HCV NS3 serine protease and can find application in treating chronic hepatic disorders, particularly chronic hepatitis.

10 cl, 1 tbl, 25 ex

FIELD: chemistry.

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EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.

14 cl, 1 tbl, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to producing new 5,8,9,10-tetrahydropyrimido[4,5-d]azocine derivatives having triflate, secondary and tertiary amino groups in the 4th position of general formula specified below. In general structural formula: 2-12 2 X=OTf (Tf means triflate), X means NR1R22 related to the groups 3-12

.

The method consists in the fact that 6-isopropyl-2-phenyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one reacts with methyl propyolate in methanol at room temperature to produce methyl 8-isopropyl-4-oxo-2-phenyl-5,8,9,10-tetrahydropyrimido[4,5-d]azocine-6-carboxylate (1). Thereafter, the prepared compound reacts with triftalane hydride in dichloromethane in the presence of pyridine at t°=-10°C; it is recovered and purified with by means of column chromatography to prepare methyl 8-isopropyl-2-phenyl-4-{[(trifluoromethyl)sulphonyl]oxy}-5,8,9,10-tetrahydropyrimido[4,5-d]azocine-6-carboxylate (2); then the solution I mmole of the prepared product (2) in absolute dioxide is added with 2 mmole of K2CO3 and 1.5 mmole of appropriate amine. After being boiled for two hours and removing the solvent, respective 4-amino substituted 5,8,9,10-tetrahydropyrimido[4,5-d]azocine of formula 3-12 is prepared. The method is directed to prepare the products in the form of white or yellow powder, or in the form of drying oil.

EFFECT: after the primary screening, the compounds appeared to be acetyl- and butyrylcholin esterase inhibitors and can find application as scaffolds in searching the preparations for treating neurodegenerative diseases.

10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new imidazo[4,5-b]pyrazine derivatives of general formula or to its pharmaceutically acceptable salt wherein: R1 represents either aryl unsubstituted or substituted by one of the groups: halogen, hydoxyl, C1-6alkyl, C1-6alkoxyl, NH2, NHC1-6alkyl, N(C1-6alkyl)2, NHC1-6alkylC1-6alkoxy, C1-6alkylhydroxy, -C(O)NH2, -C(O)OC1-6alkyl, -C(O)NH C1-6alkyl, cyano, carboxy, heteroaryl and heterocycloalkyl; or heteroaryl unsubstituted or substituted by one of the groups: C1-6alkoxy, hydroxy, -C1-6alkyl, NH2 and NHC1-6alkyl; heterocycloalkyl unsubstituted or substituted by one group =O; and R2 represents H; unsubstituted C3-4alkyl; C1-4alkyl substituted by C5-6cycloalkyl unsubstituted or substituted by one group specified in amino, hydroxyl, C1-6alkoxy, or heterocycloalkyl unsubstituted or substituted by 1-2 groups specified in =O, C1-6alkyl; or C5-6cycloalkyl substituted by one group specified in hydroxyl, C1-6alkoxyl, C1-6alkylC1-6alkoxy, C1-6alkylhydroxy, CONH2; or substituted ir unsubstituted heterocycloalkyl; wherein aryl represents an aromatic structure consisting of 6-10 carbon atoms containing one ring or two condensed rings; wherein heteroaryl represents a 5-10-member aryl ring system containing 1-2 heteroatoms specified in nitrogen, oxygen and sulphur; wherein heterocycloalkyl represents a 5-9-member nonaromatic cycloalkyl wherein 1-2 heteroatoms specified in nitrogen and oxygen; provided the compound does not represent 1,3-dihydro-5-phenyl-2H-imidazo[4,5-b]pyrazin-2-one. Also, the invention refers to the specific imidazo[4,5-b]pyrazine derivatives, to a based pharmaceutical composition, to a method of treating or preventing cancer, inflammatory conditions, immunological diseases, metabolic conditions, and to a method of kinase inhibition in a cell expressing said kinase.

EFFECT: there are produced new imidazo[4,5-b]pyrazine derivatives showing effective biological properties.

17 cl, 2 tbl, 210 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new halogenised pyrazolo[1,5-a]-pyrimidines of general formula (I) and their pharmaceutically acceptable salts possessing affinity with respect to α1-,α2 subunits of a GABAA receptor. In formula R represents alkyl(C1-C6); R1 is specified in a group consisting of alkyl(C1-C6) and alkinyl(C1-C6); X represents a halogen atom, and Y is specified in a group consisting of -CO- and -SO2. The invention refers to intermediate enamine compounds and methods for preparing them.

EFFECT: invention also refers to a method for preparing the compounds of formula (I), the based pharmaceutical compounds, to the use of said compounds for preparing said drug preparation for treating or preventing anxiety, epilepsy, sleep disorders, including insomnia, as well as for inducing a sedative-hypnotic effect, anaesthesia and muscular relaxation.

23 cl, 6 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: in formula (VIII):

X represents NR7; Y represents O or N-(CH2)nR19; n is equal to 1 or 2; m is equal to 1 or 2; R1 represents H or C1-6alkyl; R2 independently represents H, C1-6alkyl or C5-6cycloalkyl; each of R4 and R4 independently represents H or C1-6alkyl; or R4 and R4 together form spiro-C3-6cycloalkyl group; R19 represents H, C1-6alkyl, C6aryl or C3cycloalkyl group; R6 represents OR8 ; and each of R7 and R8 independently represents H or C1-6alkyl. The invention also refers to compounds of formula VI, VII, a pharmaceutical composition containing said compounds, and a method of treating a proliferative disease, such as cancer.

EFFECT: invention refers to new pyrimidine derivatives and their pharmaceutically acceptable salts possessing the properties of a PLK1 kinase inhibitor.

24 cl, 8 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula

wherein m is equal to 0, 1, 2; n is equal to 0, 1, 2, 3; each p, s, t is equal to 0 or 1; X represents CHR8 wherein R8 represents hydrogen; represents -CR9=C<, and then a dash line represents a bond, R9 independently represents hydrogen or C1-6-alkyl, or wherein R9 together with one of R2 or R20 forms a direct bond; R1 represents hydrogen; R2 and R20 are specified in: halogen, cyano, polyhalogen-C1-6-alkyl, C1-6-alkyl, morpholinyl, C1-6-alkyloxy with any of said groups is optionally and independently substituted by hydroxy, NR21R22 wherein R21 and R22 are independently specified in hydrogen, C1-6-alkylcarbonyl; or R2 and R20 together with a phenyl cycle whereto attached form a naphthaline group; or one of R2 or R20 have the values specified above, and the other of R2 or R20 together with R9 form a direct bond; R3 represents hydrogen; R4 and R5 independently represent hydrogen, C1-6-alkyl, hydroxy-C1-6-alkyl, C2-6-alkenyl or C1-6-alkyloxy; or R6 represents hydrogen; when p is equal to 1, then R7 represents hydrogen; Z represents one of the radicals presented in the patent claim. Also, the invention refers to a based pharmaceutical composition, using the compounds of formula (I) for producing the drug preparation for treating the disorders medicated by p53-MDM2 interaction for treating cancer, and to methods for producing the compounds of formula (I).

EFFECT: preparing the compounds of formula (I) as p53-MDM2 interaction inhibitors.

13 cl, 5 tbl, 31 ex

FIELD: chemistry.

SUBSTANCE: invention relates to biotechnology, specifically to obtaining modified IGF-1 proteins and can be used in medicine. Constructed is a polypeptide which contains a human IGF-1 precursor protein, wherein amino acids G1, P2 and E3 are removed as a result of deletion or amino acid E3 is removed as a result of deletion, and wherein amino acid R37 is replaced with alanine and amino acids R71 and R72 are removed as a result of deletion. The cleavage of the E-peptide from IGF-1 by a protease is reduced as a result of said modifications. The obtained polypeptide is used to treat a musculoskeletal disease, diabetes, conditions associated with neuron death, anaemia, chronic obstructive pulmonary disease and burn injury.

EFFECT: invention enables to obtain stabilised polypeptides containing a modified sequence of an IGF-1 precursor, in which the cleavage of the E-peptide from IGF1 which occurs in natural physiological conditions is reduced.

21 cl, 12 dwg, 1 tbl, 82 ex

FIELD: medicine.

SUBSTANCE: endothelial dysfunction is diagnosed if observing the twofold increase of a rat's blood glucose level. The technique involves determining antioxidant system values, a concentration of total NO metabolites, eNOS activity, a micro- and macrohaemodynamic status, a MDA concentration and Na+ K+ ATP-ase activity in myocardial and hepatic cell membranes. The values variations enables stating the presence of endothelial dysfunction in alloxan diabetes. Such dysfunction is corrected by the subcutaneous introduction of the preparation Ubiquinone (Coenzyme Q10) 0.11 mcl/100 g of animal's weight once a day for 30 days.

EFFECT: more accurate and reliable diagnosis of the vascular disorders accompanying said type of diabetes, and effective correction of such disorders also provides reproducibility, ease, availability, safety and low cost of performing the experiment.

2 cl, 2 tbl, 6 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to agonists of neuropeptide-2 receptor with formula (I): Y-R1-R2-X-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12-R13-R14-NH2(l), as well as their pharmaceutically acceptable salts, derivatives and fragments, in which substitutes assume values given in the description.

EFFECT: compounds and pharmaceutical compositions containing said compounds can be used to treat diseases which are modulated by neuropeptide-2 receptors, mainly obesity.

13 cl, 10 dwg, 1 tbl, 74 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to haematology cardiology and endocrinology, and concerns correction of blood microvesicle level in abdominal obesity. That is ensured by patient-specific hypocaloric diet combined with graduated physical exercises and preparation Orlistat introduced in a dose 120 mg 3 times a day with food intake. Therapeutic course is at least 12 weeks.

EFFECT: method enables normalisation and following maintenance of blood microvesicle level, and thereby prevention of vascular complications in patients of given category.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, pharmaceutics and food industry and concerns a medical product, foodstuff or a beverage for pancreas improvement, containing compounds 9,19-cyclolanostan-3-ol and-or 24-methylene-9,19-cyclolanostan-3-ol as an active compound, and pancreas improvement method.

EFFECT: invention ensures improved clinical effectiveness.

19 cl, 3 tbl, 2 ex

FIELD: chemistry, biochemistry.

SUBSTANCE: invention refers to biotechnology, specifically, to cell differentiation and can be used in medicine. Differentiated stromal cell is made of adipose tissue. This cell expresses one or more proteins, characteristic for endocrine pancreas cell, such as insulin, glucagon, somatostatin and pancreatic polypeptide.

EFFECT: production of differentiated and functionally relevant cell for researches, implantation, transplantation and development of tissue products for treating pancreas diseases and repairing pancreas tissues.

24 cl, 8 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, pharmacology and food industry and applies to medication, food product or drink for pancreas function improvement, which includes as active compound 4-methylholest7-en-3-ol, 4-methylergost-7-en-3-ol or 4-methylstigmast-7-en-3-ol, and method of pancreas function improvement.

EFFECT: invention ensures increased treatment efficiency.

19 cl, 3 tbl, 2 ex

FIELD: medicine, endocrinology.

SUBSTANCE: therapeutically efficient quantities of phitostanol characterised by general formula I are introduced.

EFFECT: efficient treatment of sugar diabetes due to an increase in cell sensitivity to glucose and insulin and enhancing insulin secretion by beta-cells of pancreas.

4 ex, 10 dwg, 18 cl

FIELD: medicine, gastroenterology, pancreatology, reanimation.

SUBSTANCE: method involves carrying out epidural anesthesia at the level ThIX - ThXI with 0.2% ropivacaine solution that is administrated at the rate 4-5 ml/h for 72 h. Epidural infusion is combined with intravenous administration of the preparation "Essentiale" in the dose 10 ml of solution in 200 ml of 0.9% NaCl, 2 times per 24 h. Invention provides adequate anti-stress protection and analgesic effect and with retention of motor activity of patient. Invention can be used in treatment of acute destructive pancreatitis in early period.

EFFECT: improved and enhanced effectiveness of treatment.

1 ex

FIELD: medicine, endocrinology.

SUBSTANCE: invention relates to methods used in treatment of the impaired glucose tolerance in aim for prophylaxis or postponement of invasion of insulin-independent diabetes mellitus. Variants of method involves administration in patient compounds of the formula (I) or (II) or their pharmaceutically acceptable salts describes in the invention claim, in particular, such compounds as (+)-5-[[4-[(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)methoxy]phenyl]methyl]-2,4-thiazolidinedione, pioglitazone, ciglitazone. Invention provides prevention of insulin-independent diabetes mellitus development by decrease of insulin insufficiency and normalization of tolerance to glucose in clinically health patients no having the enhanced basal levels of blood glucose.

EFFECT: improved treatment method.

9 cl, 4 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical composition and medicine, and represents a hypoglycemic, hypocholesteremic, hypolipidemic and (or) antioxidant combination of bis-(γ-L-glutamyl)-L-cysteinyl-glycine in the form of disodium salt and lipoic acid in the form of sodium salt, and coordination compounds formed by palladium, copper and γ-L-glutamyl-L-cysteinyl-glycine wherein the molar ratio of bis-(γ-L-glutamyl)-L-cysteinyl-glycine of disodium salt : sodium lipoate : palladium : copper found within the range of 100-10000:100-10000:1-10:1-10.

EFFECT: invention provides higher therapeutic effectiveness.

7 cl, 4 ex, 2 tbl

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