Derivatives of benzamide, method of their production and their application, pharmaceutical composition and method for provision of inhibiting action in respect to hdac

FIELD: medicine.

SUBSTANCE: invention is related to compound of formula (I), (values of radicals are described in formula of invention) or its pharmaceutically acceptable salts, to methods of its production, pharmaceutical composition, which contains it. Application of invention is described for manufacturing of medicinal agent intended for provision of inhibiting action in respect to HDAC in warm-blooded animal, in production of agent used for treatment of malignant tumor. Method is also described for provision of inhibiting action in warm-blooded animal.

EFFECT: compounds have inhibiting activity in respect to HDAC.

15 cl, 17 tbl, 24 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

in which ring a is a pyridyl, hinely, pyrimidinyl, morpholinyl, piperidinyl, piperazinil, pyridazinyl, pyrazinyl, thiazolyl, thienyl, thienopyrimidines, thienopyridines, purinol, triazinyl or furanyl, and if ring a contains a-NH - part, the nitrogen atom may be optionally substituted by a group selected from K;
R1is a Deputy on the carbon atom and selected from halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, N-(C1-C6-alkyl)amino, heterocyclic group, where the specified heterocyclic group denotes a saturated or unsaturated monocyclic ring containing 6 atoms, of which two atoms is represented by nitrogen, piperidinyl(C1-C6-alkyl) or group (- S-); where R1including group (b-E-), may be optionally substituted on one carbon atom W; and where if said heterocyclic group contains an-NH - part, the nitrogen atom may be optionally substituted by J;
W represents C1-C6-alkylthio, C1-C6-alkyl, C1-C6alkoxy,
N,N(C1-C6-alkyl)2amino or a group (In'-E'-); where W, including group (In'-E'-), may be optionally substituted on one carbon atom of Y;
Y and Z are independently selected from C1-C6-is laksi, N,N-(C1-C6-alkyl)2amino;
G, J and K are independently selected from C1-C8-alkyl, C2-C8-alkenyl, C1-C8alkanoyl, benzoyl, arils1-C6-alkyl or (heterocyclic group)1-C6-alkyl; where G, J and K may be optionally substituted on a carbon atom by one or two Q;
Q represents halogen, cyano, hydroxy, C1-C6-alkoxy, C1-C6-alkoxycarbonyl, C1-C6-alkoxycarbonyl or a group (B"-E"-); where Q, including group (B"-E"-), may be optionally substituted on one carbon atom Z;
B, b' and a" are independently selected from C1-C6-alkyl, C3-C8cycloalkyl, tetrahydropyranyl, (heterocyclic group)1-C6-alkyl, phenyl or panels1-C6-alkyl; where b, b' and b" can be optionally substituted on one carbon atom D; and where if said heterocyclic group contains an-NH - part, the nitrogen atom may be optionally substituted by a group selected from G;
E, e' and E" are independently selected from-N(Ra)-, -O-, -C(O)O-, -OC(O)-, -C(O)-,
-N(Ra)C(O)-, -N(Ra)C(O)O-, -OC(O)N(Ra)-, where Raselected from hydrogen or C1-C6-alkyl;
D is selected from halogen, nitro, hydroxy, C1-C6-alkoxy, N,N-(C1-C6-alkyl)2amino, C1-C6-alkane is ylamino;
m represents 0, 1 or 2, where the values of R1may be the same or different;
R2is a halogen;
n represents 0 or 1;
R3represents amino;
R represents 0;
or its pharmaceutically acceptable salt;
(i) if not stated otherwise, the heterocyclic group is a saturated or unsaturated monocyclic ring containing 5 or 6 atoms, in which 1-3 atoms independently selected from nitrogen, sulfur or oxygen, where CH2group optionally may be replaced by C(O); and (ii) aryl group represents a group selected from phenyl or naphthyl.

2. The compound of formula (I) according to claim 1, in which ring a represents a pyridine-4-yl, pyridine-3-yl, pyridin-2-yl, quinoline-8-yl, pyrimidine-6-yl, pyrimidine-5-yl, pyrimidine-4-yl, morpholine-4-yl, piperidine-4-yl, piperidine-3-yl, piperidine-2-yl, piperazine-4-yl, pyridazin-5-yl, pyrazin-6-yl, thiazole-2-yl, Tien-2-yl, thieno[3,2d]pyrimidinyl, thieno[3,2b]pyrimidinyl, thieno[3,2b]pyridinyl, purine-6-yl or triazine-6-yl; where if ring a contains a-NH - portion, a nitrogen atom optionally may be substituted by a group selected from K.

3. The compound of formula (I) according to claim 1, in which ring a represents a pyridine-4-yl, pyridyl-3-yl, quinoline-8-yl, piperidine-4-yl or piperazine-4-yl, where if ring a contains a-NH - part, the atom and the PTA optionally can be substituted by the group selected from K.

4. The compound of formula (I) according to claim 1, in which:
R1is a Deputy on the carbon atom and selected from halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, N-(C1-C6-alkyl)amino, heterocyclic group, where the specified heterocyclic group denotes a saturated or unsaturated monocyclic ring containing 6 atoms, in which two atoms are nitrogen, piperidinyl(C1-C6-alkyl) or group (- S-); where R1including group (b-E-), may be optionally substituted on one carbon atom W; and where if said heterocyclic group contains an-NH - part, the nitrogen atom may be optionally substituted by J;
W represents C1-C6-alkylthio, C1-C6-alkyl, C1-C6-alkoxy, N,N-(C1-C6-alkyl)2amino or a group (In'-E'-); where W, including group (In'-E'-), may be optionally substituted on one carbon atom of Y;
Y and Z are independently selected from C1-C6-alkoxy, N,N-(C1-C6-alkyl)2amino;
G, J and K are independently selected from C1-C8-alkyl, C2-C8-alkenyl, C1-C8alkanoyl, arils1-C6-alkyl or (heterocyclic group)1-C6-alkyl; where G, J and K may be optionally substituted on a carbon atom by one or the two Q;
Q represents a cyano, hydroxy, C1-C6-alkoxy, C1-C6-alkoxycarbonyl,
C1-C6-alkoxycarbonyl, or a group (B"-E"-); where Q, including group (B"-E"-), may be optionally substituted on one carbon atom Z;
B, b' and a" are independently selected from C1-C6-alkyl, C3-C8-cycloalkyl, tetrahydropyranyl, (heterocyclic group)1-C6-alkyl, phenyl or panels1-C6-alkyl; where b, b' and b" can be optionally substituted on one carbon atom D; and where if said heterocyclic group contains an-NH - part, the nitrogen atom may be optionally substituted by a group selected from G;
E, e' and E" are independently selected from-N(Ra)-, -O-, -C(O)O-, -OC(O)-, -C(O),
-N(Ra)C(O)-, -N(Ra)C(O)O-, -OC(O)N(Ra)-, where Raselected from hydrogen or C1-C6-alkyl;
D is selected from halogen, C1-C6-alkoxy or N,N-(C1-C6-alkyl)2amino.

5. The compound of formula (1) according to claim 1, in which m represents 1.

6. The compound of formula (1) according to claim 1, in which R2represents fluorine.

7. The compound of formula (I) according to claim 1, in which:
ring a represents a pyridine-4-yl, pyridine-3-yl, pyridin-2-yl, pyrimidine-6-yl, pyrimidine-5-yl, pyrimidine-4-yl, morpholine-4-yl, piperidine-4-yl, piperidine-3-yl, piperidine-2-yl, piperazine-4-yl, ridazin-5-yl, pyrazin-6-yl or triazine-6-yl; where if ring a contains a-NH - portion, a nitrogen atom optionally may be substituted by a group selected from K;
R1is a Deputy on the carbon atom and selected from fluorine, chlorine, amino, methyl, ethyl, propyl, methoxy, N-methylamino, N-ethylamino, N-propylamino, N-butylamino, piperazine-1-yl, piperidine-1-yl-methyl or the group (- S-); where R1including group (b-E-), may be optionally substituted on one carbon atom W; and where if said heterocyclic group contains an-NH - part, the nitrogen atom may be optionally substituted by J;
W represents a methyl, ethyl, ethoxy, N,N-(diethyl)amino, N,N-(dibutil)amino, or a group (In'-E'-); where W, including group (In'-E'-), may be optionally substituted on one carbon atom of Y;
Y and Z are independently selected from methoxy, N,N-(dimethyl)amino;
G, J and K are independently selected from methyl, ethyl, propyl, penttila, 2-methylbutyl, butyl, acetyl, benzyl, 3-(pyrrol-1-yl)propyl or pyrrolidin-2-he-(5S)-methyl; where G, J and K may be optionally substituted on a carbon atom by one or two Q;
Q represents a cyano, hydroxy, methoxy, ethoxy, methylcarbonate, methoxycarbonyl, Cretu-butoxycarbonylamino, or a group (B"-E"-); where Q, including group (B"-E"-), may be optionally substituted on one carbon atom Z;
B, b' and a" are independently selected from methyl,ethyl, propyl, cyclohexyl, phenyl, benzyl, 1,2,3,4-tetrahydroquinoline, 2-morpholinoethyl, 2-pyrrolidin-1-yl-ethyl, 3-morpholinopropan, 3-(4-methylpiperazin-1-yl)propyl, 2-piperidine-1-yl-ethyl, 3-piperidine-1-yl-propyl, pyridine-3-yl-methyl or imidazol-1-yl-propyl; where b, b' and b" can be optionally substituted on one carbon atom D; and where if specified heterocyclic group contains an-NH - part, the nitrogen atom may be optionally substituted by a group selected from G;
E, e' and E" are independently selected from-N(Ra)-, -O-, -C(O)-, -NHC(O)-, -N(Ra)C(O)O-; where Rarepresents hydrogen or methyl;
D is selected from fluorine, methoxy or ethoxy;
m represents 0, 1 or 2; where the values of R1may be the same or different;
R2represents fluorine;
n represents 0 or 1;
R-represents amino;
R represents Oh,
or its pharmaceutically acceptable salt.

8. The method of obtaining the compounds of formula (I) or its pharmaceutically acceptable salt, including
the interaction of the compounds of formula (II)

where X represents a reactive group with a compound of formula (III)

where L1and L2represent ligands;
and then, if necessary, conversion of the compounds of formula (1) into another compound of formula (1) is/or removing any protective groups.

9. The method of obtaining the compounds of formula (1) or its pharmaceutically acceptable salt, including
the interaction of the compounds of formula (IV)

where L1and L2represent the ligand with the compound of the formula (V)

where X represents a reactive group;
and then, if necessary, conversion of the compounds of formula (1) into another compound of formula (1) and/or removing any protective groups.

10. The method of obtaining the compounds of formula (1) or its pharmaceutically acceptable salt, including
interaction in the presence of chloride 4-(4,6-dimethoxy-1,3,5-triazinyl-2-yl)-4-methylmorpholine, the compounds of formula (VI)

with the compound of the formula (VII)

and then, if necessary, conversion of the compounds of formula (I) into another compound of the formula and/or removing any protective groups.

11. Pharmaceutical composition having inhibitory activity against HDAC, which contains a compound of the formula (I)or its pharmaceutically acceptable salt according to any one of claims 1 to 7 in combination with a pharmaceutically acceptable diluent or carrier.

12. The compound of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 7, intended for use as a drug is, possessing activity against HDAC.

13. Application of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 7 in the manufacture of a medicinal product that is intended to provide inhibitory effect against HDAC warm-blooded animal such as man.

14. The way to ensure inhibitory effect against HDAC warm-blooded animal such as man that is in need of such treatment, comprising the introduction of a specified animal an effective amount of the compounds of formula (I) or its pharmaceutically acceptable salt according to any one of claims 1 to 7.

15. The use of the compounds of formula (I) or its pharmaceutically acceptable salt according to claims 1 to 7 for the preparation of medicines used for the treatment of malignant neoplasms.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I)

, where R is selected from ethyl, n-propyl, iso-propyl, n-butyl and allyl; R' is selected from hydrogen, straight, branched or cyclic C1-C4alkyl; straight, branched or cyclic C1-C3alkoxy; fluorine, chlorine, bromine, trifluoromethyl and OCHxFy, where x=0, 1, 2, y=1, 2, 3 under the condition that, x+y=3; R" is selected from hydrogen, fluorine and chlorine, with the condition that, R" is selected from fluorine and chlorine only when R' is selected from fluorine and chlorine; R3 is selected from hydrogen and straight, branched or cyclic C1-C5alkyl; R4 is selected from hydrogen, CH2OCOC(CH3)3, pharmaceutically acceptable inorganic or organic cations, and COR4', where R' is straight, branched or cyclic C1-C5alkyl, phenyl, benzyl or phenethyl; R7 is selected from methyl and ethyl; one of A and B is sulphur, and the other is C-R2; when A is S, R2 is selected from hydrogen and methyl, with the condition that R2 is methyl only when R3 is not hydrogen; and when B is S, R2 is hydrogen; and to any tautomer thereof, as well as to a pharmaceutical composition which contains formula (I) compound, to a method of producing said compounds and to a method of treating diseases which are a result of autoimmune response or pathologic inflammation.

EFFECT: new compounds are disclosed, which can be used in treating diseases which are a result of autoimmune response or pathologic inflammation.

35 cl, 2 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: in formula compounds, each of R1, R2, R3, R4 is a substitute for a cyclic system, chosen from hydrogen, halogen, C1-C6-alkyl; C1-C6-alkoxy group; X is a heteroatom, chosen from oxygen or sulphur; R5 and R6 independently represent amino group substitutes, chosen from hydrogen, possibly substituted C1-C6-alkyl; possibly substituted C3-C6-cycloalkyl, which can be annealed with a benzene ring; possibly substituted phenyl, which can be annealed with dioxole, dioxine, -(CH2)n group, where n=4 to 6, or with a 5 or 6-member possibly substituted and possibly condensed azaheterocyclyl; possibly substituted saturated or unsaturated 5-6-member heterocyclyl, containing 1-2 heteroatoms, chosen form nitrogen, oxygen, sulphur and possibly condensed with a benzene ring, or R5 and R6 together with the nitrogen atom to which they are bonded, form an optionally substituted 5 or 6-member azahetero ring, possibly containing an additional heteroatom, chosen from nitrogen, and possibly annealed with a benzene ring or spiro-condensed with dioxole, where substitutes in the said alkyl, cycloalkyl, phenyl and heterocyclyl are chosen from halogen atoms, possibly substituted C1-C6-alkyl, CF3, possibly substituted C3-C6-cycloalkyl, possibly substituted phenyl, 5 or 6-member heterocyclyl, nitro group, substituted amino group, alkyloxycarbonyl, substituted carbonyl, aminocarbonyl, alkylsulphanyl.

EFFECT: design of an efficient method of producing new substituted furo[2,3-b]quinoline-2-carboxamides and substituted thieno[2,3-b]quinoline-2-carboxamides or their racemates, or their optical isomers, as well as their pharmaceutically acceptable salts and/or hydrates of general formula (I), which have antituberculous activity.

9 cl, 1 dwg, 7 tbl, 5 ex

FIELD: pharmacology.

SUBSTANCE: invention concerns indazol derivatives of general formulae (I) or (II) , where radicals and groups are defined as shown in cl. 1 of invention claim, and their pharmaceutically acceptable salts. Also invention claims medicine, method of medicine obtainment and application of claimed compounds in treatment and/or prevention of fatty acid metabolism derangement and glucose assimilation disorders.

EFFECT: inhibition of hormone-sensitive lipases.

13 cl, 1 tbl, 103 ex

FIELD: medicine.

SUBSTANCE: invention relates to the method for production of the compound of the formula (1a), being an inhibitor of thrombocyte aggregation (1a), where X is halogen atom. The method includes interaction of compounds of the formula (II), (II), where X has above mentioned value and Y and Z independently from each other are leaving groups, with optically active alkamine with formation of diastereoisomers admixture.

EFFECT: development of the new advantageous method for production of the bioactive compound.

48 cl, 24 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to novel derivatives of 2,6-dihydro-7H- pyrazolo[3,4-d]pyradazin-7-one, 1,4-dihydropyrazolo[3,4-b]thiazin-5(6H)-one; N-acylated 4-imidazo[1,2-a]pyridin-2-yl- and 4-imidazo[1,2-a]pyrimidin-2-yl- anilines; amides of [(4H-thieno[3,2-b]pyrrol-5-yl)carbonyl]pyperidin-4-carboxylic acid; amides of 2-(4-carbamoylpyperidin-1-yl)isonicotinic acid; amides of N-sulfonyl-1,2,3,4-tetrahydrochinolin-6-carboxylic acid; as well as to N-acylated 3-azolyl derivatives of 2-amino-4,5,6,7-tetrahydtithieno[2,3-c]pyridine possessing properties of Hh-signal cascade inhibitors.

EFFECT: compounds can be applied for use in pharmaceutical compositions and medications for treating diseases induced by abberant activity of Hedgehog (Hh) signal system, in particular, oncological diseases, for instance, for pancreatic carcinoma treatment.

23 cl, 13 dwg, 11 tbl, 26 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the method for preparation of hexachloroantimonates of 2,3-dihydro[1,3]thiazolium of general formula wherein R1 is alkyl or phenyl, R2 is alkyl, phenyl or hydrogen, R1+R2 is cycloalkyl by the interreaction of 4,6-dimethyl-2-pyrimidinsulfenyl chloride with corresponding olefine in presence of antimony pentachloride in equimolar ratio in the media of methylene chloride.

EFFECT: claimed compounds can be used in production of pharmaceutical preparations and biologically active substances.

2 ex

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 ex

Thienopyrazoles // 2358978

FIELD: chemistry.

SUBSTANCE: description is given of thienopyrazol of formula I its pharmaceutically acceptable salts or esters, in which X represents N or C-R7; X1 represents N or C-R1; R1, R2, R3, R4, R5 and R6 are independently chosen from a group which contains hydrogen, possibly substituted acyl, alkyl, alkoxy group, acylaminogroup, alkoxyalkyl, (Y1)(Y2)NC(=O)-, alkoxycarbonyl, aryl, halogen, carboxy group; or R5 and R6 together with two carbon atoms with a double bond, with they are bonded, form a benzene ring; R7 is a hydrogen atom, halogen or alkyl; and Y1 and Y2 are independently a hydrogen atom, alkyl, aryl or heteroaryl, or Y1 and Y2 together with a nitrogen atom, with which they are bonded, form a heteroaryl group or heterocycloalkyl group. The invention also relates to pharmaceutical compositions, containing these compounds. Thienopyrazoles can be used for treating diseases, which can be affected by protein kinase inhibition, particularly, interleukin-2-induced tyrosine kinase.

EFFECT: wider field of application of the compounds.

14 cl, 1 tbl, 98 ex

FIELD: chemistry.

SUBSTANCE: invention refers to Clopidogrel process by optical separation of its racemic form with using optically active amine of formula V to make optically active form of compound of formula III or its acid-additive salt followed with methylation of compound III or its salts. The intermediate product of formula resulted from reaction of racemic form of Clopidogrel and amine V.

EFFECT: possibility to make a high-yield end product.

22 cl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new spirocyclic cyclohexane derivatives of general formula I , where: R1-R3, R5-R10, W, X are disclosed in the claim 1 of formula.

EFFECT: compounds exhibit analgesic activity to be applied for making a medical product for pain therapy.

20 cl, 1 tbl, 54 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to substituted 8-heteroarylzantines of general formula where R represents hydrogen, (C1-C5)alkyl or halogen(C1-C8)alkyl; R1 is chosen from (C3-C6)cycloalkyl or (C3-C6)cycloalkyl(C1-C4)alkyl-; R2 is chosen from (C1-C8)alkyl, (C3-C8)alkenyl, (C3-C8)alkinyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl- or (C6-C10)aryl(C1-C8)alkyl-; X represents 3-pyridyl substituted in 6th position with Z; Z represents -NR4R5 or (C4-C10)heterocycle where heterocycle is optionally substituted with 1, 2, 3 or 4 substitutes independently chosen from (C1-C8)alkyl; each Z1 independently represents halogen or -NR7R8; R5 is chosen from -C(O)R6, -CO2R6 or -C(O)NHR7; R4 is chosen from hydrogen, (C1-C8)alkyl, (C3-C8)cycloalkyl, (C3-C8)cycloalkyl(C1-C8)alkyl-, (C3-C10)heterocycle(C1-C8)alkyl-, (C6-C10)aryl, (C6-C10)aryl(C1-C8)alkyl-, (C5-C10)heteroaryl, (C5-C10)heteroaryl(C1-C8)alkyl-, -((CH2)2-4)Y)q-(CH2)2-4-X1, -C(O)R6, -CO2R6 or -C(O)NR7R8; or R4 and R5 together with atoms whereto attached form saturated mono-or bicyclic ring with 5, 6, 7 or 8 ring atoms and optionally containing 1 or 2 heteroatoms chosen of non-peroxide oxy (-0-) and amine -N(R9)- in the ring where the ring is optionally substituted by 1, 2, 3 or 4 substitutes independently chosen from -C(O)Ra and -C(O)NRbRc; X1 represents -OR6; and Y represents oxy (-O-); where alkyl, alkenyl, cycloalkyl, alkinyl, aryl, heterocyclic or hetero aryl groups from R1, R2, R3, R4 and R5 groups are optionally substituted by one or more substitutes independently chosen from (C1-C8)alkyl, -ORa, (C6-C10)aryl, hydroxy(C1-C8)alkyl and RbRcN(C1-C8)alkyl; where R6 represents (C1-C8)alkyl or (C4-C10)heteroaryl; where heteroaryl is optionally substituted by 1, 2, 3 or 4 substitutes independently chosen from halogen, -ORa and halogen(C1-C8)alkyl; where R7, R8 and R9 independently represent (C1-C8)alkyl, RaO(C1-C8)alkyl, (C6-C10)aryl or (C4-C10)heteroaryl; where heteroaryl or aryl are optionally substituted by 1, 2, 3 or 4 substitutes independently chosen from halogen and -ORa; Ra represents hydrogen or (C1-C6)alkyl; each Rb and Rc independently represents hydrogen or (C6-C10)aryl; and where n is equal to 0, 1 or 2; and q is equal to 1; or its pharmaceutically acceptable salt. In addition, the invention concerns pharmaceutical composition based on compound of formula I.

EFFECT: new substituted 8-heteroarylxantines are selective antagonists of A2B adenosine receptors.

38 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the formula I , where R0 is 1) monocyclic 6-14-member aryl, where aryl is independently mono-, di- or trisubstituted by R8, 2) heterocyclyl out of group of benzothiazolyl, indazolyl, pyridyl, where the said heterocyclyl is independently non-substituted or mono-, di- or trisubstituted by R8, and other radicals referred to in point 1 of the claim; R8 is halogen; on condition that R8 is at least one halogen atom if R0 is monocyclic 6-14-member aryl; substructure in the formula I is 4-8-member saturated, partly non-saturated or aromatic cyclic group including 0, 1 heteroatom selected out of nitrogen or sulfur, and is non-substituted or substituted 1, 2, 3 times by R3; Q is -(C0-C2)alkylene-C(O)NR10-, methylene; R1 is hydrogen atom, -(C1-C4)alkyl, where alkyl is non-substituted or substituted one to three times by R13; R2 is a direct link; R1-N-R2-V can form 4-8-member cyclic group selected out of piperazine or piperidine group; R14 is halogen, =O, -(C1-C8)alkyl, -CN; V is 1) 6-14-member aryl, where aryl is independently non-substituted or mono-, di- or trisubstituted by R14, and other radicals referred to in point 1 of the claim; G is direct link, -(CH2)m-NR10, where m is 0 and R10 is hydrogen, -(CH2)m-C(O)-(CH2)n-, where m is 0 or 1, and n is 0, -(CH2)m-C(O)-NR10-(CH2)n-, where m is 0 or 1, and n is 0, 1 or 2, -(CH2)m-, where m is 1; M is 1) hydrogen atom, 2) 6-14-member aryl, and other radicals referred to in point 1 of the claim; R3 is 1) hydrogen atom, 2) halogen atom, 3) -(C1-C4)alkyl, where alkyl is non-substituted, and other radicals referred to in point 1 of the claim; R11 and R12 are independently the same or different and are 1) hyfrogen atom, 2) -(C1-C6)alkyl, where alkyl is non-substituted or monosubstituted by R13, and other radicals referred to in point 1 of the claim; or R11 and R12 can form 4-8-member monocyclic heterocyclic ring together with nitrogen atoms to which they are linked, and beside the nitrogen atom the ring can include one or two similar or different ring heteroatoms selected out of oxygen, sulfur and nitrogen; where the said heterocyclic ring is independently non-substituted or mono-, disubstituted by R13; R13 is halogen, =O, -OH, -CF3, -(C3-C8)cycloalkyl, -(C0-C3)alkylene-O-R10; R10 is hydrogen, -(C1-C6)alkyl; R15 and R16 are independently hydrogen, -(C1-C6)alkyl; R17 is -(C1-C6)alkyl, -(C3-C8)cycloalkyl; in all stereoisomer forms and their mixes at any ratio, and physiologically tolerable salts. Compounds of the formula I are reversible inhibitors of enzyme factor Xa (FXa) and/or factor VIIa (FVIIa) of blood clotting, and can be generally applied in states accompanied by undesirable factor Xa and/or factor VIla activity, or supposing factor Xa and/or factor VIla inhibition for treatment or prevention. In addition, invention concerns methods of obtaining compounds of the formula I, their application as agents in pharmaceutical compositions.

EFFECT: obtaining compounds applicable as agents in pharmaceutical compositions.

19 cl, 1 tbl, 169 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new derivatives of hydrochloride 8-amino-7-(2-hydroxypropyl-1)-1,3-dimethylxanthine of general formula: where . Compounds under this invention display haemorheological activity surpassing that of common pentoxifylline compound. Compounds represent hydrochloride 1,3-dimethy-7-(2-hydroxy-3- piperidinopropyl-1)-8-phenylaminoxanthine or hydrochloride 1,3- dimethy-7-[2-hydroxy-3-(2- chlorophenoxy)-propyl-1]-8- piperazinoxanthine.

EFFECT: production of compounds displaying haemorheological activity.

4 cl, 2 tbl, 4 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to application as ligands of 5-NT6 receptor azaheterocyclic compositions of general formula 1 or their racemates, or their optical isomers, or their pharmaceutically acceptable salts and/or hydrates , where R2 and R3 independently represent substitute of amides chosen from hydrogen; substituted carbonyl; substituted aminocarbonyl; substituted aminothiocarbonyl; substituted sulphonyl; C1-C5-alkyl, optionally substituted with C6-C10-aryl, optionally substituted with heterocyclil, C6-C10-arylaminocarbonyl, C6-C10- arylaminothiocarbonyl, C5-C10-azaheteroaryl, optionally substituted with carboxyl, nitrile group; optionally substituted with aryl; R1k are 1 to 3 independent substitutes to cyclic system chosen from hydrogen, optionally substituted C1-C5-alkyl, C1-C5-alkyloxy, C1-C5-alkenyl, C1-C5- alkenyl, halogen, trifluoromathyl, nitrile, carboxyl, optionally substituted heterocyclil, substituted sulphonyl, optionally substituted carboxyl; dashed line with accompanying continuous line () corresponds to single or double bond; n=1.2 or 3. Invention also concerns a pharmaceutical formulation, production method and tabletted, capsulated or injection medical product in pharmaceutically acceptable package.

EFFECT: agent has improved efficiency.

17 cl, 8 tbl, 5 ex, 1 dwg

The invention relates to new chemical substances suitable for use as medicaments, in particular to the xanthine derivative of General formula I

R3where R1and R2lower alkyl;

R3the rest of the group, including tetrahydrofurane, thiophene, dithiolane, dithienyl, furan, optionally substituted by a group: -CH2OH, CHO, COOH,

-CH=where Alk denotes alkyl with 1-4 carbon atoms,

-CH=CH-CO-NO,

-CONHN-CH< / BR>
-CH=C< / BR>
-CH=C< / BR>
-CONH-(CH2)2N(Alk)2where Alk has the specified value, tetrahydrofuran, optionally substituted lower alkyl or the group-CH2CH2-CO-NO, or furan or thiophene, substituted lower alkyl or nitro-group or the unsubstituted cycloalkyl with 6-8 carbon atoms, cycloalkane or ticlea, alseny of Gruppman2,N,NH-phenyl, whereby phenyl may be substituted,NOH, -OCONH-phenyl, and phenyl may be samisens-COOCH3, -CH2COOCH3, -CH2CH2NH2, -OC(C6H5)3, -OALK, where Alk has the specified value, ОСОR4where R4matter: the rest campanulas acid, lower alkyl, phenyl, substituted lower alkoxyl, phenyl, methoxymethyl, six-membered nitrogen-containing heterocycle; cyclohexane, substituted cyanomethylene or oxyalkyl1-C4or hydroxy-group, or cyclopentane, substituted lower alkyl or phenyl, which may have as a second Deputy in genialnom position relative to the first hydroxyl group or ketal formula

or R3residue selected from the group:

(CH2)1,2< / BR>
ororin VI

FIELD: chemistry.

SUBSTANCE: present invention relates to use of compounds of formula (I) where R1 is lower alkyl or halogen; R2 is hydrogen or halogen; R3 is (CHR')nOH, phenyl, possibly substituted with a -(CHR')nOH group, or is a saturated, partially saturated or aromatic 5- or 6-member heterocyclic ring with one heteroatom, selected from a group which consists of -N(R4)-, -N=, -S- or -S(O)2, where the rings are possibly substituted with a -(CHR')nOH group; R' is hydrogen or a -(CH2)nOH, independent of the value of n; R4 is hydrogen, -S(O2)-lower alkyl group or -C(O)-lower alkyl; X is -O-, -CH2O-, -S- or a bond; n equals 1 or 2; or their pharmaceutically active acid addition salts for making medicine for treating schizophrenia, as well as to compounds of formula (I).

EFFECT: description is given of compounds which can be used in medicine.

8 cl, 16 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: new 5-sulphanyl-4H-1,2,4-triazole derivatives of general formula I (meaning of radicals R1-R3 are indicated in the description of the invention), methods of their preparation by liquid-phase parallel synthesis and pharmaceutical composition are claimed.

EFFECT: claimed compounds display high affinity to some subtypes of somostatin receptors of the SST2 and SST5 subtypes and possibility of their usage for treatment of pathological states or diseases involving one or more of the given somostatin receptors

9 cl, 708 ex

FIELD: chemistry; medicine.

SUBSTANCE: in novel triazole derivatives of general formula I or their pharmaceutically acceptable salts R4 is hydrogen; X is selected from group, consisting of single bond, NH- and groups: , values of R1-R3 radicals are given in description, pharmaceutical composition containing them, and application of novel compounds for obtaining medication for treating hyperglycemia, insulin-resistance, type 2 diabetes, fat exchange derangements, obesity, atheroslerosis and metabolic syndrome.

EFFECT: medications possess higher efficiency.

26 cl, 8 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: claimed invention relates to compounds of formula (I), their obtaining and application as elastase inhibitors, and can be applied in medicine, where Y = CH; R№ represents H or alkyl; RІ represents phenyl or 5-6-memner heteroaryl, G1 represents phenyl; R5 represents H, halogen, alkyl, CN or fluorinated alkyl; n=1-3; R4 = H; L represents bond, O, NR29 or alkyl; or R4 and L are bound together in such way that group -NR4L- represents 5-7-member asacyclic ring; G2 represents phenyl, 5-6-member heteroaryl, cycloalkyl, C4-7-heterocycle, bicycle from two condensed, bound with direct bond or separated with O atom rings, selected from phenyl, 5-6-member heteroaryl, cycloalkyl or C4-7-heterocycle; or when L does not represent bond, G2 represents H; s = 0-2; R25 represents H, alkyl or cycloalkyl; R29 represents H or alkyl.

EFFECT: obtaining novel biologically active compounds.

10 cl, 95 ex, 1 tbl

FIELD: chemistry; pharmacology.

SUBSTANCE: invention refers to new benzofuran and benzothiophen derivatives of general formula I, , wherein X is chosen from O and S; R1 is chosen from H, (C1-C6)alkyl, C(O)(C1-C6) alkyl and benzoyl; R2 is chosen from phenyl optionally substituted with 1 or 2 substitutes, each independently chosen from CN, NO2, (C1-C6)alkyl, (C1-C6)alkoxy, halogen, halogen(C1-C6)alkyl, pyridyl or benzo[1,3]dioxolyl optionally substituted with (C1-C6)alkyl. There are disclosed pharmaceutical composition based on compounds I and method of treatment.

EFFECT: compounds can be used to treat or prevent diseases associated with malignant cell proliferation.

26 cl, 7 tbl, 365 ex

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