Chemical compounds

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of formula (I): , in which: R1 and R2 are independently specified from hydrogen, C1-6alkyl, C1-6alkoxy and cyclopropyl; X1, X2 and X3 independently represent =N- or =CR10; R3 and R10 are independently specified from hydrogen, halogen, nitro, cyano, amino, carboxy, carbamoyl, C1-6alkyl, N-(C1-6alkyl)amino, N,N(C1-6alkyl)2amino, C1-6alkanoylamino, C1-6alkoxycarbonyl; R4 represents hydrogen; R5 and R6 are independently specified from hydrogen, hydroxy and C1-6alkyl where R5 and R6 independently can be optionally substituted in carbon atom with one or more R16 where R16 represents hydroxy; A represents a single link or C1-2alkylene; where specified C1-2alkylene can be optionally substituted with one or more R18; the ring C represents a saturated, partially saturated or unsaturated mono- or bicyclic ring containing 5 or 6 atoms in which at least one atom can be specified from nitrogen, sulphur or oxygen which can be linked with carbon or nitrogen atom where the -CH2- group can be optionally substituted with -C(O)- and ring sulphur atom can be optionally oxidised to produce S-oxide; R7 is specified from halogen and C1-6alkyl where R7 can be optionally substituted in carbon atom with halogen; n is equal to 0.1 or 2; where R7 values can be equal or different; and R18 is independently specified from halogen and hydroxy; or its pharmaceutically acceptable salt. Also the invention refers to their pharmaceutical compositions and methods for preparation and application thereof for cancer treatment.

EFFECT: preparation of new compounds which can find application for cancer treatment.

23 cl, 96 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

in which
R1and R2independently selected from hydrogen, C1-6of alkyl, C1-6alkoxy and cyclopropyl is;
X1X2and X3independently represent an =N - or =CR10-;
R3and R10independently selected from hydrogen, halogen, nitro, cyano, amino, carboxy, carbamoyl,1-6of alkyl, N-(C1-6alkyl)amino, N,N(C1-6alkyl)2amino, C1-6alkanolamine,1-6alkoxycarbonyl;
R4represents hydrogen;
R5and R6independently selected from hydrogen, hydroxy and C1-6of alkyl, where R5and R6independently of each other optionally may be substituted at carbon atoms by one or more R16where R16represents hydroxy;
Rather it represents a simple bond or a C1-2alkylen where the specified C1-2alkylene optionally may be substituted by one or more R18;
the ring is a saturated, partially saturated or unsaturated mono - or bicyclic ring containing 5 or 6 atoms in which at least one atom may be selected from nitrogen, sulphur or oxygen, which may be associated with a carbon atom or nitrogen, CH2group optionally may be replaced by-C(O)-and a ring sulphur atom may not necessarily be oxidized with the formation of S-oxide;
R7selected from halogen and C1-6of alkyl, where R7optionally may be substituted at a carbon atom by halogen;
n equal to 0.1 ili; where the values of R7may be the same or different;
R18independently selected from halogen and hydroxy; or its pharmaceutically acceptable salt.

2. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R1represents isopropoxy.

3. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R2represents hydrogen.

4. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R3selected from hydrogen, cyano, carbamoyl,1-6the alkyl and C1-6alkoxycarbonyl; where R3optionally may be substituted at carbon atoms by one or more R13; and R13represents hydroxy.

5. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where R5and R6independently selected from hydrogen, methyl and hydroxymethyl.

6. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where a represents a simple bond or a C1-2alkylen where specified With1-2alkylene optionally may be substituted by one or more R18where R18represents hydroxy.

7. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1, where the ring is a phenyl, pyridyl, pyrimidinyl, 1,3-benzodioxolyl or 1H-indolyl.

8. The compound of formula I or its pharmaceutically acceptable salt according to claim 1, where R7selected from halogen and C1-6of alkyl, where R7optionally may be substituted at carbon atoms by one or more R20where R20represents a halogen.

9. The compound of formula (I)

in which
R1selected from methyl, isopropoxy and cyclopropyl;
R2represents hydrogen;
X1X2and X3independently represent an =N - or =CR10-;
R3selected from hydrogen, cyano, carbamoyl, methyl, hydroxymethyl and methoxycarbonyl;
R10selected from hydrogen, fluorine, chlorine, cyano, carbamoyl, methyl, aminomethyl and acetamidomethyl;
R4represents hydrogen;
R5selected from hydrogen, methyl, ethyl or hydroxymethyl;
R6selected from hydrogen or hydroxymethyl;
Rather it represents a simple bond, methylene or hydroxymethylene;
the ring is a phenyl, pyrid-2-yl, pyrimidine-2-yl, 1,3-benzodioxol-5-yl or 1H-indol-3-yl;
R7represents trifluoromethyl, and fluoro; and
n represents 0, 1 or 2; where the values of R7may be the same or different;
or its pharmaceutically acceptable salt.

10. The compound of formula (I)

selected from
(2R)-2-[9-(5-cyclopropyl-1H-pyrazole-3-yl)-6-methyl-N-purine-2-ylamino]-2-(4-forfinal)ethanol;
(2R)-2-{[-(5-cyclopropyl-1H-pyrazole-3-yl)-N-purine-2-yl]amino}-2-(4-forfinal)ethanol;
N((S)-1-(4-forfinal)ethyl)-9-(5-isopropoxy-1H-pyrazole-3-yl)-N-purine-2-amine;
3-(5-cyclopropyl-1H-pyrazole-3-yl)-N-[(S)-1-(4-forfinal)ethyl]-3H-imidazo[4,5-b]pyridine-5-amine;
3-(5-isopropoxy-1H-pyrazole-3-yl)-N-((S)-1-(pyridine-2-yl)ethyl)-3H-imidazo[4,5-b]pyridine-5-amine;
N-((S)-1-(4-forfinal)ethyl)-3-(5-isopropoxy-1H-pyrazole-3-yl)-3H-imidazo[4,5-b]pyridine-5-amine;
(2R)-2-(4-forfinal)-2-(3-(5-isopropoxy-1H-pyrazole-3-yl)-3H-imidazo[4,5-b]pyridine-5-ylamino)ethanol;
6-chloro-N-((S)-1-(4-forfinal)ethyl)-3-(5-isopropoxy-1H-pyrazole-3-yl)-3H-imidazo[4,5-b]pyridine-5-amine;
3-(5-cyclopropyl-1H-pyrazole-3-yl)-N-[(S)-1-(4-forfinal)ethyl]-3H-benzo[d]imidazol-5-amine; and
N-((1-(5-cyclopropyl-1H-pyrazole-3-yl)-6-((S)-1-(4-forfinal)ethylamino)-1H-benzo[d]imidazol-5-yl)methyl)ndimethylacetamide;
or its pharmaceutically acceptable salt.

11. The method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salts, in which variable groups have the meanings indicated in claim 1, unless specifically stated otherwise, where the method includes
the way in) for compounds of formula (I)in which X1is a =CR10; the interaction of the compounds of formula (V)

with the compound of the formula (VI)

and then, if necessary
i) removing any protective groups; and/or
ii) formation of pharmaceutically acceptable salts.

12. The compound of formula (I) or its pharmaceutical is citiesi acceptable salt according to claim 1, for use as drugs having inhibitory activity against Trk kinase.

13. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1 for preparing a medicinal product intended for the inhibition of Trk activity.

14. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1 for the preparation of drugs for treatment or prevention of malignant tumors.

15. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1 for the preparation of a medicinal product to obtain antiproliferative action.

16. The method of inhibition of Trk activity, which includes the introduction of a host in need of such treatment, a therapeutically effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to claim 1.

17. A pharmaceutical composition comprising a compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 together with at least one pharmaceutically acceptable carrier, diluent or excipient for the inhibition of Trk activity.

18. A pharmaceutical composition comprising a compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 together with at least one pharmaceutically acceptable but what ielem, diluent or excipient for the treatment or prevention of malignant tumors.

19. A pharmaceutical composition comprising a compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 together with at least one pharmaceutically acceptable carrier, diluent or excipient to obtain antiproliferative action in warm-blooded animal such as man.

20. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 for the inhibition of Trk activity.

21. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 for the treatment or prevention of malignant tumors.

22. The compound of formula (I) or its pharmaceutically acceptable salt according to claim 1 to obtain antiproliferative action.

23. The application 14, where the specified malignant neoplasm selected from congenital fibrosarcoma, adenomyosarcoma, mesothelioma, acute myeloblastic leukemia, acute lymphocytic leukemia, multiple myeloma, melanoma, oesophageal cancer, myeloma, liver cell carcinoma, pancreatic cancer, cervical cancer, diffuse endothelioma bones, neuroblastoma, Kaposi's sarcoma, ovarian cancer, breast cancer including secretory breast cancer, colorectal cancer, prostate cancer, including hormone-rez is stenny prostate cancer, bladder cancer, melanoma, lung cancer - non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), gastric cancer, head and neck cancer, kidney cancer, lymphoma, thyroid cancer, including papillary thyroid cancer, mesothelioma and leukemia.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of N-(5-[3-(thiophene-2-carbonyl)-pyrazole[1,5-a]pyrimidin-7-yl]-2-fluoro-phenyl}-N-methyl-acetamide in polymorphic modification B, in which (5-amino-1H-pyrazol-4-yl)-thiophen-2-yl-methanone reacts with N-[5-(3-dimethylamino-acryloyl)-2-fluoro-phenyl]-N-methyl-acetamide in a solvent selected from a group comprising acetic acid, propionic acid and methanoic acid at 50°C until boiling point of the mixture is reached. (C1-C4)-alcohol is then added to the obtained mixture at temperature of 40°C-80°C, after which the obtained mixture is kept for at least 30 minutes a temperature of 30°C- 55°C for initiating crystallisation. The crystalline product is then separated.

EFFECT: method of obtaining a compound in polymorphic modification B, which can be used in medicine in treating and preventing anxiety, epilepsy, sleep disorders and insomnia.

8 cl, 3 dwg, 1 tbl, 1 ex

FIELD: chemistry.

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EFFECT: method for synthesis of novel derivatives having potential anticancer activity.

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound - a sodium salt of 2-ethylthio-6-nitro-1,2,4-triazole[5,1-c]-1,2,4-triazin-7-one dihydrate of formula (1)

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EFFECT: higher antiviral activity which can be used in medicine, stockbreeding and poultry farming.

2 tbl

FIELD: medicine, pharmaceutics.

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5 cl, 25 dwg, 7 tbl, 16 ex

FIELD: medicine, pharmaceutics.

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30 cl, 371 ex, 4 tbl

FIELD: chemistry.

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EFFECT: improved properties of compounds.

10 cl, 2 dwg, 1 tbl, 129 ex

FIELD: chemistry.

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1 cl, 1 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-substituted 3-(2-chloro-1H-indol-3-yl)-4-phenyl-1H-pyrrole-2,5-diones of formula 1: , where R1 denotes H, C1-C6alkyl; R2 denotes compounds which, under the effect of visible light, form fluorescent 2,8-substituted benzo[a]pyrrolo[3,4-c]carbazole-1,3-(2H,8H)diones of formula II: , where R1 and R2 are as described above.

EFFECT: more effective use of the compounds.

10 cl, 2 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medication, reducing desire for alcohol, which represents substituted 1H-benzimidazoles of general formula 1 or their pharmaceutically acceptable salts and/or hydrates, pharmaceutical composition, and medication on their basis. Compounds can be applied in treatment of alcohol abuse with application of ethanol-containing products, if necessary, together with antidepressants. In compounds of general formula 1 , where: W represents sulfur atom or group S=O; R1 represents one or more substituents, selected from hydrogen, halogen, C1-C4alkyl, C1-C4alkyloxy, optionally substituted 5-6-member azaheterocyclyl with 1-2 atoms of nitrogen and/or oxygen in cycle; R2 represents atom of hydrogen or optionally substituted C1-C4alkyl; R3 and R4 independently on each other represent optionally similar substituents, selected from hydrogen, optionally substituted C1-C4alkyl, C3-C6cycloalkyl; R5 represents alkyl substituent, selected from hydrogen or optionally substituted C1-C7alkyl, C1-C7alkenyl, C1-C4alkynyl, optionally substituted phenyl, optionally substituted 5-6-member heterocyclyl with 1-3 heteroatoms, selected from nitrogen, oxygen and sulfur, possibly condensed with benzene ring; C1-C4-alkoxycarbonyl, optionally substituted amino carbonyl, or group CR3R4R together stands for group , where Alk stands for C1-C4alkyl.

EFFECT: medication allows to reduce symptoms of alcohol abuse considerably as compared with earlier known compounds and does not produce unfavorable effect on liver function.

12 cl, 3 tbl, 2 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to pyrrolotriazines of formula (I) , where R1 is selected from a group which includes phenyl, naphthyl, benzyl and heteroaryl, which denotes a mono- or bicyclic radical containing 5-10 ring atoms and up to 2 heteroatoms selected from a group consisting of nitrogen, oxygen and sulphur, at least one ring of which is aromatic, where, if necessary, phenyl and heteroaryl may be substituted with 0, 1 or 2 substitutes independently selected from a group consisting of -(C1-C4)alkyl, where -(C1-C4)alkyl can be substituted with 0, 1, 2 or 3 halogens, 0 or 1 pyrrolidine, -(C1-C3)alkoxy group, where, if necessary, the (C1-C3)alkoxy group may be substituted with a (C1-C3)alkylamino group, halogen, trifluoromethyl, trifluoromethoxy group, phenyl, if necessary substituted with 1 or 2 halogens, - , where X denotes O, nitro group, - (C1-C3)alkylthio group, trifluoromethylthio group, - (C1-C3)alkylcarbonyl, - (C1-C6)alkoxycarbonyl, and a phenoxy group, and where the benzyl can be substituted with 0, 1, 2 or 3 groups selected from a group which includes halogen; R2 is selected from a group consisting of hydrogen, halogen; R3 is selected from a group consisting of carboxyl, - (C1-C6)alkylcarbonyl, - (C3-C6)cycloalkylcarbonyl, - (C1-C6)alkoxycarbonyl, if necessary substituted with 0, 1, 2 or 3 groups selected from a group which includes amino group and (C1-C6)alkoxycarbonyl; aminocarbonyl, -(C1-C6)alkylaminocarbonyl, where (C1-C6)alkylaminocarbonyl which, if necessary, can be substituted with 0, 1, 2 or 3 substitutes independently selected from a group consisting of (C3-C6)cycloalkyl, halogen, amino group, (C1-C6)alkylamino group, hydroxy group, (C1-C6)alkoxy group, (C1-C6))alkoxycarbonyl, (C1-C6)alkylthio group, (C1-C6)alkoxycarbonylamino group,and where, if necessary, (C1-C6)alkylaminocarbonyl may be substituted with 0 or 1 heterocyclyl, which denotes a monocyclic, non-aromatic radical containing 5-8 ring atoms and up to 2 heteroatoms selected from nitrogen and oxygen, where, if necessary, the hetecyclyl may be substituted with 0 or 1 (C1-C6)alkyl, heterocyclylcarbonyl, if necessary substituted with 0 or 1 (C1-C6)alkylamino group, cycloalkyl or (C1-C6)alkyl,where, if necessary, (C1-C6)alkyl may be substituted with 0 or 1 (C1-C6)alkylamino group, and where heterocyclyl denotes a monocyclic, non-aromatic radical containing 5-8 ring atoms and up to 2 heteroatoms selected from nitrogen and oxygen, -(C1-C6)alkyl if necessary substituted with 0, 1 or 2 substitutes independently selected from a group consisting of a) hydroxyl, b) (C1-C6)alkylamino group, where (C1-C6)alkylamino group may be substituted with 0, 1 or 3 substitutes independently selected from a group consisting of halogen, alkylamino group, methoxy group, methylthio group and methylsulphonyl, c) phenylamino group, where the phenylamino group may be substituted with 0, 1 or 2 substitutes independently selected from a group consisting of (C1-C6)alkoxy group and trifluoromethyl, d) heterocyclyl, where heterocyclyl denotes a monocyclic, non-aromatic radical containing 5-8 ring atoms and up to 2 heteroatoms selected from nitrogen and oxygen, and where the heterocyclyl may be substituted with 0 or 1 (C1-C6)alkyl, where (C1-C6)alkyl may be substituted with 0 or 1 methoxy groups or pyridyls, e) imidazolyl, f) pyridylamino group, g) (C1-C3)alkoxy group, if necessary substituted with fluorine or piperidine,where, if necessary, the piperidine may be substituted with 0 or 1 (C1-C6)alkyl, h) (C1-C3)alkoxy(C2-C3)alkoxy group, and i) (C1-C6)alkoxycarbonyl, j) (C3-C6)cycloalkyl, k) cyano group, - (C3-C6)cycloalkylaminocarbonyl, cyano group, heteroaryl, where heteroaryl denotes a monocyclic radical containing 5-6 ring atoms and up to 3 heteroatoms selected from a group consisting of nitrogen and oxygen, the ring of which is aromatic, where the heteroaryl may be substituted with 0, 1 or 2 groups independently selected from a group consisting of q) (C1-C6)alkyl, where the (C1-C6)alkyl may be substituted with 0 or 1 morpholine or 0 or 1 hydroxy group, r) (C1-C6)alkoxycarbonyl, thiophene carbonyl, and R4 is selected from a group consisting of hydrogen; to a pharmaceutically acceptable salt thereof. The invention also pertains to methods of obtaining said compounds.

EFFECT: obtaining novel compounds which can be used in medicine for preventing or treating hyper-proliferative disorders and diseases associated with angiogenesis.

5 cl, 313 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I in free form or in form of pharmaceutically acceptable salt, which possess properties of adenosine receptor A2A agonists. In formula I , R1 represents (C1-C8)alkylcarbonyl, (C3-C8)cycloalkylcarbonyl, -SO2(C1-C8)alkyl, phenyl(C1-C4)alkylcarbonyl or -(C=O)-C(=O)-NH(C1-C8)alkyl, optionally substituted with R4; R2 represents H or (C1-C8)alkyl, optionally substituted with (C6-C10)aryl; R3 represents halogen or(C2-C8)alkinyl, or R3 stands for aminogroup, optionally substituted with (C3-C8)cycloalkyl, optionally substituted with amino, or R3 represents (C1-C8)alkylaminogroup, optionally substituted with hydroxy, phenyl or R5, or R3 stands for R6, optionally substituted with amino or -NH-C(=O)-NH-R7, or R3 stands for -NH-R6, optionally substituted with -NH-C(=O)-NH-R7, or R3 stands for (C1-C8)alkylaminocarbonyl, optionally substituted with. -NH-C(=O)-NH-R8; R4, R5 and R6 represent independently 5- or 6-member heterocyclic ring, which contains one-two N ring heteroatoms, optionally substituted with amino or (C1-C8)alkyl; and R7 and R8 represent independently 5- or 6-member heterocyclic ring, which contains one-two ring heteroatoms selected from N and S, and is optionally substitutedf with halogen, (C1-C8)alkylsulfonyl or 5- or 6-member aromatic heterocyclic ring, which contains one N ring heteroatom. Invention also relates to pharmaceutical composition and to application of said compounds for treatment of states, mediated by activation of adenosine receptor A2A.

EFFECT: obtaining composition, which possesses properties of adenosine receptor A2A agonists.

10 cl, 3 tbl, 80 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel purine derivatives of general formula I in free form or in form of a pharmaceutically acceptable salt which have A2A agonist properties. In formula I , R1 denotes a N-bonded 5-6-member heterocyclic group containing 1-4 nitrogen atoms in the ring, which can be optionally substituted with oxo, phenyl or C1-8-alkyl, optionally substituted with hydroxy; R2 is hydrogen or C1-C8-alkyl, optionally substituted with hydroxy or 1-2 phenyls possibly substituted with hydroxy or C1-C8-alkoxy; R3 is C2-C8-alkynyl or C1-C8-alkoxycarbonyl, or R3 is amino substituted with C3-C8-cycloalkyl, optionally substituted with amino, hydroxy, benzyloxy or NH-C(=O)-NH-R6, or R3 is amino substituted with R4, -R4-benzyl or C5-C10-mono- or bicarbocyclic group, optionally substituted with hydroxy or C1-C8-alkoxycarbonyl, or R3 is aminocarbonyl optionally substituted with R5, or R3 is C1-C8-alkylamino optionally substituted with hydroxy, R5, NH-C(=O)-C1-C8-alkyl, -MH-SO2-C1-C8-alkyl, -NH-C(=O)-NH-R6 or phenyl, optionally substituted with phenyloxy, or R3 is a N-bonded 5-member heterocyclic group containing 1 nitrogen atom in the ring which may optionally be substituted with amino, C1-C8-alkylamino, di(C1-C8-alkyl)amino and other groups.

EFFECT: compounds can be useful in treating conditions mediated by activation of the adenosine A2A receptor, especially inflammatory or obstructive respiratory tract diseases.

9 cl, 5 tbl, 161 ex

FIELD: chemistry.

SUBSTANCE: in compounds of formula (I) , Q is: (IIa) or (IIb) , R1 is chosen from a group which consists of carboxylic aryl and carboxylic aryl which is substituted with substitute(s) independently chosen from a group which consists of halogen, cyano, nitro, C1-10alkyl, C1-10alkyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-9alkoxy, C1-9alkoxy which is substituted with substitute(s) independently chosen from a group which consists of halogen, mono-C1-5alkylamino, and heterocyclyl or heterocyclyl which is substituted with substitute(s) independently chosen from a group which consists of halogen, C1-5alkyl; R2 is C1-5alkyl, C1-5alkyl which is substituted with halogen, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, -N(R2a)(R2b); where R2a and R2b are each independently hydrogen, C1-5alkyl or C1-5alkyl, substituted with substitute(s) independently chosen from a group which consists of hydroxyl, carboxylic aryl; L represents formula (IIIa); , where R3 and R4 are each hydrogen; A is a single bond, and B is a single bond or -CH2-; Z1, Z3, and Z4 are each independently hydrogen, halogen, C1-5alkyl, C1-5alkyl, substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Z2 is hydrogen, C1-5alkyl, C1-5alkyl which is substituted with carboxylic aryl, C1-5alkoxy, mono-C1-5alkylamino, di-C1-5alkylamino, carboxylic aryl, heterocyclyl or substituted heterocyclyl; Y is -C(O)NH-, -C(O)-, -C(S)NH-, -C(O)O- or -CH2-; where carboxylic aryl is phenyl; heterocyclyl is 1H-indolyl, 9H- xanthenyl, benzo[1,3]dioxolyl, furyl, imidazolyl, isoxazolyl, morpholinyl, piperazinyl, pyridyl, pyrrolidyl; halogen is fluorine, chlorine, bromine or iodine. The invention also relates to a pharmaceutical composition.

EFFECT: compounds can be used for treating central nervous system diseases, and for improving memory functioning, sleep, awakening, diabetes.

16 cl, 8 dwg, 4 tbl, 525 ex

Comt inhibitors // 2354655

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula I where R1 stands for H, CN, halogen, -COR2, -S(O)xR2, C1-C12alkyl, C2-C12alkenyl, C3-C8dicloalkyl, aryl group, heteroaryl group standing for 5- or 6-merous aromatic mono- or bicyclic heterocyclic group with 1-2 heteroatoms, chosen of N or S, C3-C8cycloalkyl-(C1-C3)alkyl or group aril-(C1-C3)alkyl; alkyl, alkenyl, cycloalkyl, aryl and heteroaryl groups can be optionally substituted with halogen, C1-C6alkyl, group-COR2; R2 stands for -N(R3,R3'), C1-C6alkyl, C3-C8cycloalkyl, aryl, heteroaryl which stands for 5- or 6-merous aromatic mono- or bicyclic heterocyclic group with 1-2 heteroatoms chosen of N, C3-C8cycloalkyl-(C1-C3) alkyl or aril-(C1-C3)alkyl; C1-C6alkyl, C3-C8cycloalkyl, aryl, heteroaryl can be optionally substituted with halogen, C1-C6alkyl; R3 and R3' independently stands for hydrogen or (C1-C3)alkyl; x stands for 0, 1 or 2; and also to their esters, hydrolyzed in physiological environment, and to their pharmaceutically acceptable salts. The invention also concerns a medical product.

EFFECT: production of new biologically active compounds active as COMT inhibitor.

17 cl, 19 ex, 1 tbl

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides novel N6-substituted adenine-based heterocyclic compounds depicted by general formula I: , for which meanings of radicals are presented in description, and pharmaceutically acceptable salts thereof manifesting anticancer, mitotic, immunosuppressive, and antiaging activities for vegetable, animal, and human cells, and methods for preparation thereof. Included are also pharmaceutical compositions, cosmetic preparations, and growth regulators, which contain indicated derivatives as active components. Application of indicated derivatives for preparing therapeutical preparations, and cosmetic preparations are also described.

EFFECT: expanded synthetic possibilities in adenine series and increased choice of various biologically active agents.

10 cl, 10 dwg, 9 tbl, 14 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of piperidine of the general formula (I): or their pharmaceutically acceptable salts wherein rings A and B represent optionally substituted benzene rings; R1 represents alkyl, hydroxyl, thiol, carbonyl, sulfinyl, unsubstituted or substituted sulfonyl group and others; R2 represents hydrogen atom, hydroxyl, amino-group, alkyl, unsubstituted or substituted carbonyl group or halogen atom; Z represents oxygen atom or group -N(R3)- wherein R3 and R4 represent hydrogen atom or alkyl group under condition that N-acetyl-1-benzyloxycarbonyl-2-phenyl-4-piperidineamine is excluded. Compounds of the formula (I) or their salts possess antagonistic activity with respect to tachykinin NK1-receptors and can be used in medicine in treatment and prophylaxis of inflammatory, allergic diseases, pain, migraine, diseases of central nervous system, digestive organs and others.

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

18 cl, 138 tbl, 527 ex

The invention relates to the derivatives of purine, which has antiviral activity against human cytomegalovirus and human immunodeficiency virus type 1, of General formula:

where n = 0 to 4; m = 0 to 3; R1= N, HE or NH2; R2= HE, NH2, acetylamino or benzoylamine; R3= H or lower alkyl (C1-C4; R4= H, lower alkyl (C1-C4or phenyl; X = CH2, O, S, NH or C(O)O; and Y = CH2, CH=CH, C(O), or ordinary communication; Ar = phenyl, pyridyl, naphthyl or substituted phenyl of the formula

where independently R5-R9= alkyl1-C8cycloalkyl C5-C6, 1-substituted, allyl, phenyl, benzyl, F, Cl, Br, J, trifluoromethyl, alkoxy, C1-C5phenoxy, benzyloxy, benzoyloxy, cyano, carboxy, acetyl, or nitro, antiviral effect of the most active compounds against human cytomegalovirus in vitro manifests itself in concentrations of 0.01-0,0005M and is characterized by selectivity 1-400 thousand

The invention relates to new compounds of General formulas I, II, III

< / BR>
or their pharmaceutically acceptable salts, in which the dotted lines indicate optional double bonds; A is-CR7or N; - - NR1R2, -CR1R2R11, -C(= CR2R12R1, -NHCHR1R2, -ОСHR1R2, -SCHR1R2, -CHR2OR12,

-CHR2SR12, -C(S)R2or-C(O)R2N-ethyl-2,2,2-triptorelin; G is oxygen, sulfur, NH, NH3hydrogen, methoxy, ethoxy, triptoreline, methyl, ethyl, dimethoxy, NH2, NHCH3N(CH3)2or trifluoromethyl; Y Is N; Z is NH, O, S, -N(C1-C2alkyl) or-C(R13R14), where R13and R14independently of one another represent hydrogen, trifluoromethyl or methyl, or one of the elements of R13and R14is cyano and the other is hydrogen or stands; R1- C1-C6alkyl which may be optionally substituted by one or two substituents R8independently from each other selected from the group comprising hydroxy, fluorine, chlorine, bromine, iodine, CF3C1-C4alkoxy, -O-CO-(C1-C4alkyl), where (C1-C2- C1-C12alkyl, aryl or -(C1-C4alkylene)aryl, where aryl is phenyl, naphthyl; R3is methyl, ethyl, fluorine, chlorine, bromine, iodine, cyano, methoxy, OCF3, methylthio, methylsulphonyl, CH2HE or CH2OCH3; R4is hydrogen, C1-C4alkyl, fluorine, chlorine, bromine, iodine, C1-C4alkoxy, triptoreline, -CH2OCH3, -CH2OCH2CH3, -CH2CH2OCH3, -CF3, amino, nitro, -NH(C1-C4alkyl), -N(CH3)2, -NHCOCH3, -NHCONHCH3, hydroxy, -CO(C1-C4alkyl), -Cho, COOH, cyano, or-COO(C1-C4alkyl), where C1-C4the alkyl may be substituted by one Deputy chosen from the group comprising hydroxy, amino, -NHCOCH3, -NH(C1-C2alkyl), -N(C1-C2alkyl)2, fluorine, chlorine, cyano, nitro; R5is phenyl, naphthyl, pyridyl, pyrimidyl, where each of the above groups R5substituted with one to three substituents that are independently from each other selected from fluorine, chlorine, C1-C6the alkyl or C1-C6alkoxyl, or one Deputy chosen from the group comprising hydroxy, iodine, bromine, formyl, cyano, nitro, trifluoromethyl, amino, -(C1-C6these groups of R5may be optionally substituted with one hydroxy-group; R6is hydrogen or C1-C6alkyl; R7is hydrogen, methyl; R11is hydrogen, hydroxy, fluorine or methoxy; R12is hydrogen or C1-C4alkyl, and R16and R17independently of one another represent hydrogen, hydroxy, methyl, ethyl, methoxy or ethoxy, except that both R16and R17cannot both be methoxy or ethoxy; or R16and R17together form oxo (=O) group; provided that if G is an atom of oxygen, sulfur, NH or NCH3he is joined by a double bond to a five-membered ring of the formula III, and further provided that R6is absent when the nitrogen atom to which it is linked, is attached by a double bond to an adjacent carbon atom in the ring

The invention relates to novel 2,6,9-triple-substituted purine derivative of General formula I, having the effect of selective inhibitors of kinases of the cell cycle, which can be used, for example, for the treatment of, for example, autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, diabetes type I, multiple sclerosis, and for the treatment of cancer, cardiovascular diseases such as restenosis, etc

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula where: R1 denotes -OR1', -SR1", 6-member heterocycloalkyl with one O atom and possibly one N atom, phenyl or 5-member heteroaryl with two N atoms, 6-member heteraryl with one N atom; R1'/R1" denote C1-6-alkyl, C1-6-alkyl substituted with a halogen, -(CH2)x-C3-6cycloalkyl or -(CH2)x-phenyl; R2 denotes S(O)2-C1-6-alkyl, -S(O)2NH-C1-6-alkyl, CN; denotes the group: , and where one extra N atom of the nucleus of an aromatic or partially aromatic bicyclic amine may be present in form of its oxide ; R3 - R10 denotes H, halogen, C1-6-alkyl, C3-6cycloalkyl, 4-6-member heterocycloalkyl with one N or O atom, 6-member heterocycloalkyl with two O atoms or two N atoms, 6-8-member heterocycloalkyl containing on N atom or one O or S atom, 5-member heteroaryl with two or three N atoms, 5-member heteroaryl with one S atom, in which one carbon atom may be also substituted with N or O, 6-member heteroaryl with one or two N atoms, C1-6-alkoxy, CN, NO2, NH2, phenyl, -C(O)-5-member cyclic amide, S-C1-6-alkyl, -S(O)2-C1-6-alkyl, C1-6-alkyl substituted with halogen;C1-6-alkoxy substituted with halogen, C1-6-alkyl substituted with OH, -O-(CH2)y-C1-6-alkoxy, -O(CH2)yC(O)N(C1-6-alkyl)2, -C(O)-C1-6-alkyl, -O-(CH2)x-phenyl, -O-(CH2)x-C3-6cycloalkyl, -O-(CH2)x-6-member heterocycloalkyl with one O atom, -C(O)O-C1-6-alkyl, -C(O)-NH-C1-6-alkyl, -C(O)-N(C1-6-alkyl)2, 2-oxa-5-aza-bicyclo[2.2.1]hept-5-yl or 3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl; R' and R'" in group (e) together with -(CH2)2- with which it is bonded can form a 6-member ring; R, R', R" and R"' independently denote H, C1-6-alkyl; and where all groups - phenyl, cycloalkyl, cyclic amine, heterocycloalkyl or 5- or 6-member heteroaryl, as defined for R1, R1', R1" and R3 - R10, can be unsubstituted or substituted with one or more substitutes selected from OH, =O, halogen, C1-6-alkyl, phenyl, C1-6-alkyl substituted with halogen, or C1-6-alkoxy; n, m o, p, q, r, s and t = 1 , 2; x =0, 1 or 2; y = 1 , 2; and their pharmaceutically acceptable acid addition salts.

EFFECT: compounds have glycine transporter 1 inhibiting activity, which enables their use in a pharmaceutical composition.

20 cl, 2 tbl, 12 dwg, 382 ex

FIELD: medicine.

SUBSTANCE: invention refers to new derivatives of dihydro-pyrroloquinoline of formula I where values of R1, R2, R3a and R3c radicals are specified in cl. 1 of the patent claim. Also the invention refers to a method for making the compound of formula I, to its application, a composite product based on the compound of formula I and a general antimicrobial agent and a pharmaceutical composition based on the compound of formula I.

EFFECT: there are prepared new derivatives of dihydro-pyrroloquinoline exhibiting antibacterial activity.

26 cl, 4 dwg, 11 ex

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