Compounds as ccr-1 antagonists

FIELD: chemistry.

SUBSTANCE: described are compounds of formula (I) or their pharmaceutically acceptable salts, where symbols assume values given in the description, where the said compounds are chemokine receptor (CCR-1) antagonists. Also described is a method of inhibiting the chemokine receptor to reduce inflammation in mammals.

EFFECT: possibility of use in treating inflammatory diseases.

8 cl, 160 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I or its pharmaceutically acceptable salt

where R1, R2 and R3 are independently selected from the group consisting of hydrogen, halogen,
nitro or optionally substituted oxy,1-7of alkyl, amino, sulfur, imidazolidine, phenyl, pyridinyl, pyrazinyl;
R4 is selected from halogen;
X represents-CH=SNA-;
Y represents -(CH2)n-where n has a value of 1-6, -CH2OCH2- or-CH2NRCH2and connected with two cyclic carbon atoms, and the binding occurs or cyclic carbon atoms a and b or cyclic carbon atoms c and d; where R is selected from the group consisting of H, optionally substituted C1-7of alkyl, carbonyl, acetyl or sulfonyl;
Z represents N or-CH-;
Q represents-CH2- or-NH-;
where Z represents N, Q represents CH, and when Z represents-CH-, Q pre which represents an-NH-;
optional substituents in R1-R4 are one or more, for example, 1-3 substituent, independently selected from the group consisting of
oxo or optionally substituted by hydroxy, C1-7of alkyl, C3-7alkenyl, amino, sulfonyl;
where the optionally substituted substituents are optionally substituted one or more times, for example, 1 to 2 substituents, where the Deputy independently selected from the group consisting of hydrogen, oxo, cyano, halogen, C1-7of alkyl, amino, C3-7cycloalkyl, geterotsiklicheskie, which represents a monocyclic hydrocarbon containing from 3 to 5 atoms in the ring and 1-2 heteroatoms selected from O or N.

2. The compound of formula I according to claim 1, where R1 represents optionally substituted amino, guanidino, sulfonyl, sulfonamide, and optional substituents selected from the group consisting of oxo, or optionally substituted hydroxy, C1-7of alkyl, C3-7alkenyl, amino, sulfonyl, cyano;
where the optionally substituted substituents are optionally substituted by one or more substituents independently selected from the group consisting of hydrogen, oxo, halogen, C1-7of alkyl, amino, C3-7cycloalkyl, geterotsiklicheskie, which represents a monocyclic hydrocarbon containing from 3 to 5 atoms in the ring and 1-2 heteroatoms selected from O or N

3. The compound of formula I according to claim 1 or 2, where R2 is selected from the group consisting of methoxy, triptoreline, phenyl, pyridinyl, pyrazinyl, C1-7the alkyl.

4. The compound according to claim 1 or 2 having the formula II, or pharmaceutically acceptable salt
where R1and R2" are independently selected from the group consisting of hydrogen, halogen, nitro or optionally substituted oxy, 1-7 alkyl, amino, sulfur, imidazolidine, phenyl, pyridinyl, pyrazinyl;
X represents-CH=SNA-;
Y represents -(CH2)n-where n has a value of 1-6, -CH2Core;- or-CH2NRCH2-and is linked with two cyclic carbon atoms, and the binding occurs or cyclic carbon atoms a and b or cyclic carbon atoms c and d; where R is selected from the group consisting of H, optionally substituted With 1-7 alkyl, carbonyl, acetyl or sulfonyl;
Z represents N or-CH-;
Q represents-CH2- or-NH-;
where Z represents N, Q represents CH, and when Z represents-CH-, Q represents-NH-;
optional substituents in R1and R2" are one or more, for example, 1-3 substituent, independently selected from the group consisting of oxo, or optionally substituted hydroxy, C1-7of alkyl, C2-7alkenyl, the Mino, sulfonyl;
where the optionally substituted substituents are optionally substituted one or more times, for example, 1 to 2 substituents, where the Deputy independently selected from the group consisting of hydrogen, oxo, cyano, halogen, C1-7of alkyl, amino, C3-7cycloalkyl, geterotsiklicheskie, which represents a monocyclic hydrocarbon containing from 3 to 5 atoms in the ring and 1-2 heteroatoms selected from O or N.

5. The compound of formula 1A or its pharmaceutically acceptable salt

where R1', R2' and R3' are independently selected from the group consisting of hydrogen, halogen,
optionally substituted amino;
R4' is selected from halogen;
X' represents-och2CO-;
Y' represents-CH2Och2;- or-CH2NRCH2-and is linked with two cyclic carbon atoms, and the binding occurs or cyclic carbon atoms a and b or cyclic carbon atoms c and d, where R is selected from the group consisting of H and optionally substituted C1-7of alkyl;
Z' represents N;
Q' represents a-CH2-;
an optional substituent in the R1'-R3' is one Deputy, selected from
With1-7the alkyl, optionally substituted by oxo.

6. The compound according to any one of claims 1, 2, 5 with antagonistical the th activity against chemokine receptor 1 (CCR-1).

7. The compound according to any one of claims 1, 2, 5, intended for the treatment of inflammation.

8. A method of inhibiting chemokine receptor 1 (CCR-1) to reduce inflammation in a mammal in need of such treatment, which includes the introduction of a specified subject an effective amount of a compound according to any one of claims 1 to 5.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relate to oxabispidinic compounds of formula I, ,where R1 is C1-12alkyl (where the given alky group is substituted with a group selected from phenyl, Het1, N(R5a)R6, -OR5c, -S(O)2N(R9b)R9c and -N(R9b)S(O)2R9d); R5a is H; R5c is C1-6alkyl (which is substituted with phenol) or phenyl; R6 is H or -C(O)OR10b; R10b is C1-6alkyl; R9b in each case where it is used in the given description of the invention represents H or C1-6alkyl; R9c and R9d in each case it is used in the given description of the invention independently presents C1-6alkyl (possibly substituted with one or more substitutes, selected from halogen or phenyl), phenyl or Het7, or R9c is H; R2 is H or OR13; R3 is H; R13 is H; Het1 and Het7 independently represent 5-12-member heterocyclic groups containing one or more heteroatoms, selected from oxygen and nitrogen, where these groups are possibly substituted with one or more substitutes selected from halogen and C1-6alkyl; A is a direct bond, -J-, J-S(O)2N(R19b)- or -J-N(R19c)S(O)2- (where in the last two groups -J is bonded to the nitrogen of an oxabispidinic ring); B is Z-{[C(O)]aC(H)(R20a)}b-, -Z-[C(O)]cN(R20b)-, -Z-N(R20c)S(O)2-, -Z-S(O)2N(R20d)-, -Z-S(O)n-, -Z-O- (where in the last six groups Z is bonded to a carbon atom, carrying R2 and R3), -N(R20e)-Z-, -N(R20f)S(O)2-Z-, -S(O)2N(R20g)-Z- or -N(R20h)C(O)O-Z- (where in the last four groups Z is bonded to a phenyl group which is possibly substituted with a R4 group); J is C1-6alkylene, possibly broken by a -S(O)2N(R19d)- or -N(R19e)S(O)2- group and/or possibly substituted with a substitute selected form -OH; Z is a direct bond or C1-4alkylene, possibly broken by a -N(R20i)S(O)2- or -S(O)2N(R20j)- group; a, b and c possibly represent 0 or 1; n is 0, 1 or 2; R19b-R19e in each case where used in the given description of the invention independently represents H or C1-6alkyl; R20a is H or together with the only substitute R4 on the position of the phenyl group, which is an ortho-position relative the position where group B is bonded, represents C2-4alkylene, possibly broken or ending with O, N(H) or N(C1-6alkyl) group; R20b is H or C1-6alkyl; R20c-R20j in each case when used in the given description of the invention independently represents H or C1-6alkyl; or R20g and R20i independently represent C1-6alkyl, substituted with 3,5-dimethylisoxazolyl; G is CH; R4 is one or more possible substitutes selected from cyano, halogen, C1-4alkyl and C1-6alkoxy, possibly substituted with one or more hanogen and a R4 substitute on the position of the phenyl group, which is an ortho-position relative the position where group B is bonded, together with R20a can represent C2-4alkylene; broken or ending with O or N(H) or a N(C1-6alkyl) group; R41-R46 independently represent H; where each phenyl group is possibly substituted with one or more substitutes selected from halogen, cyano, C1-6alkyl and C1-6alkoxy (where the last two groups are possibly substituted with one or more halogen atoms); or to their pharmaceutically acceptable salts. The invention also relates to methods of producing said compounds, as well as to a pharmaceutical composition based on said compounds, with HERG-channel blocking activity.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine for preventing and treating arrhythmia, particularly cardiac and ventricular arrhythmia.

32 cl, 1 tbl, 15 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention pertains to new layers of acidic compounds with Formula I , where R2 is C1-6alkyl (possibly substituted and/or ending with one or more substitute, chosen from -OH, halogen, cyano, nitro and aryl) or aryl, where each aryl group, if not specifically mentioned, is possibly substituted by one or more substitutes, including -OH, cyano, halogen, nitro, C1-6alkyl, C1-6alkoxy, -N(R14a)R14b, -C(O)R14c, -C(O)OR14d, -C(O)N(R14e)R14f, -N(R14g)C(O)R14h, -N(R14m)S(O)2R13b, -S(O)2Rl3c and/or -OS(O)2R13d, where radicals from R13b to Rl3d independently represent C1-6alkyl; R14a and R14b independently represent H, C1-6alkyl, or jointly represent C3-6alkene, as a result, yielding a four-heptatomic nitrogen containing ring; radicals from R14c to R14m independently represent H or C1-6alkyl; A represents , where R16 represents unsubstituted C1-4alkyl, C1-4perfluoroalyl or phenyl, where the last group can be substituted with one or more substitutes, chosen from C1-6alkyl, halogen, nitro and C1-6alkoxy. The invention also relates to the method of obtaining Formula II compounds.

EFFECT: obtaining of new intermediate compounds and their use in special obtaining of formula II oxabispidin compounds, which can be used in the treatment of cardiac arrhythmia.

8 cl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel solid formulation of anti-arrhythmic medicinal agents. Invention describes crystalline formulation of 4-({3-[7-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl]propyl}amino)-benznitrile, tert.-butyl-2-{7-[3-(4-cyanoanilino)propyl]-9-oxa-3,7-dizabicyclo[3.3.1]non-3-yl}ethylcarbamate, tert.-butyl-2-{7-[4-(4-cyanophenyl)butyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethylcarbamate or tert.-butyl-2-{7-[(25)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethylcarbamate and their pharmaceutically acceptable salts. Also, invention describes methods for their synthesis, a pharmaceutical preparation based on thereof, a method for prophylaxis or treatment of arrhythmia and their using.

EFFECT: valuable medicinal properties of compounds and pharmaceutical preparation.

73 cl, 22 dwg, 22 tbl, 23 ex

FIELD: organic chemistry, antibiotics, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing 3-aminorifampicin-S representing semi-product in synthesis of anzamycine antibiotics, such as rifabutin - an anti-tuberculosis antibiotic with prolonged effect. Invention describes a method for preparing3-aminorifampicin-S that involves interaction of 3-bromorifampicin-S with hexamethylenetetramine in the amount 2-6-fold molar excess of hexamethylenetetramine with respect to 3-bromorifampicin-S at temperature 40-65°C in organic solvent medium and isolation of the end product. Trichloroethylene is used as a solvent in preparing 3-aminorifampicin-S followed by its change for butyl acetate by addition of butyl acetate to reaction mass in the amount 2-5-fold excess with respect to trichloroethylene volume followed by distilling off trichloroethylene. Prepared 3-aminorifampicin-S butyl acetate solution is filtered through aluminum oxide layer and 3-aminorifmapicin-S is isolated by evaporation until dry. Also, invention describes variant of method for preparing 3-aminorifampicin-S. Invention provides reducing reaction time in preparing the end product, reduced cost and simplified reaction, enhanced yield and purity of the end product.

EFFECT: improved method for preparing.

2 cl, 2 tbl, 20 ex

FIELD: organic chemistry, chemical technology, antibiotics.

SUBSTANCE: invention relates to methods for preparing derivatives of 3-aazidorifamycin S eliciting antibiotic properties. Method for preparing 3-azido-derivatives of rifamycin S involves interaction rifamycin S derivative with hydrazoic acid salt in solvent medium by stirring reagents at temperature from 0oC to 100oC for 0.5-2 h followed by extraction of the end product. 3-Halogen-derivative of rifamycin S is used as rifamycin S derivative. Simple aliphatic alcohols with carbon atom number from 1 to 5 or acetonitrile, or mixture of water and organic solvent not mixing with water taken among the series: ethyl acetate, methyl acetate, benzene or its mono- or dimethyl analogues, chlorinated hydrocarbons with carbon atom number from 1 to 3 is used as a solvent. Sodium azide or potassium azide is used as hydrazoilc acid salt. Extraction of the end product is carried out by extraction with solvent not mixing with water or by dilution of reaction mixture with water followed by filtration. The claimed method provides enhancing the yield of the end product by 63-71% and to simplify the process of it isolating. Invention provides the enhancement of effectiveness of method for preparing 3-azido-derivatives of rifamycin S due to elevating yield of the end product and simplifying the process of its isolating.

EFFECT: improved preparing method.

1 tbl, 13 ex

FIELD: organic chemistry, chemical technology, antibiotics.

SUBSTANCE: invention relates to a method for preparing derivatives of 3-aminorifamycin S of the formula (I) , eliciting antibiotic properties wherein X means NH2; Y = Z and mean hydrogen atom (H) or (CH3)2C<, or C6H5CH<, or C6H10<. Method for preparing 3-amino-derivatives of rifamycin S involves stirring 3-halogen-derivative of rifamycin S in solvent medium wherein solvent represents simple aliphatic alcohols with carbon atom number from 1 to 5 or acetonitrile, or mixture of water and organic solvent not mixing with water taken among the following series: ethyl acetate, methyl acetate, benzene or its mono- or dimethyl analogues, chlorinated hydrocarbons with carbon atom number from 1 to 3 with hydrazoic acid salt wherein sodium azide is used and stirring is carried out for 0.5-2 h. Then method involves the following conversion of obtained 30azido-derivative of rifamycin S to the end product using a reducing agent wherein mixture of zinc or iron with acetic acid is used, or hydrogen in the presence of palladium catalyst followed by treatment with oxidizing agent wherein ferric (III) chloride or manganese (IV) oxide is used, or hydrogen peroxide, or persulfates, or air. Extraction of the end product is carried out by extraction with organic solvent not mixing with water or by dilution of reaction mixture with water followed by crystallization of product. Invention provides the enhancement of method for preparing 3-amino-derivatives of rifamycin S due to elevating yield of the end product and process for it isolating.

EFFECT: improved preparing method.

1 tbl, 4 ex

The invention relates to a derivative phthalazine General formula (I) or their pharmaceutically acceptable salts, or hydrates, where R1and R2are the same or different from each other and each represents a halogen atom, a C1-C4alkyl group which may be substituted by a halogen atom, a hydroxyl group or a C1-C4alkoxygroup, which may be substituted by a halogen atom, or cyano; X represents a cyano, a halogen atom, hydroxyimino, optional O-substituted C1-C4alkyl group, or a heteroaryl group selected from thiazoline, thienyl, pyrazolidine, triazolinones and tetrazolyl groups that may be substituted WITH1-C4alkyl group; Y represents a cyclic amino group (i) - (v) described in paragraph 1 of the claims; (vi) etinilnoy or ethyl group substituted WITH1-C4alkyl group, which, in turn, replaced by a number of deputies referred to in paragraph 1 of the claims; (vii) optionally substituted phenyl group; (viii) pyridyloxy or thiazolidine group

FIELD: medicine.

SUBSTANCE: there are described new diazabicyclic aryl derivatives of general formula (I), where A', A", L and B, n possess the values as specified in the description which are cholinergic ligands to nicotinic acetylcholine receptors, as well as a based pharmaceutical composition. Owing to their pharmacological profile, the compound according to the invention, can be effective in treating such various diseases or disorders, as those associated with the cholinergic system of central nervous system (CNS), peripheral nervous system (PNS), as those associated with plain muscle contraction, endocrine diseases or disorders, neurodegenerative diseases or disorders, diseases or disorders involving inflammation, pain and abstinence symptoms caused by termination of abusing the chemical substances.

EFFECT: effective with regard to various diseases.

16 cl, 3 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention refers to the new compounds of formula (I): whereat R1 is -SO2NR102R103, -NR101SO2R104 or -COOR105 whereat R101 is hydrogen atom, R102 and R103 each independently represents hydrogen atom or C1-4 alkyl, R104 is C1-4 alkyl and R105 is hydrogen atom or C1-4 alkyl ; X is bond, -CH2- or -O-; Y is -CH2-; ring A and ring B, which are same or different, each independently is benzene, pyridine, pyrazol or piperidine which can have the following substituents: C1-4 alkyl or halogen; ring D is piperidine; R2 is whereat the arrow shows the position of the bond with the ring D; R51 is (1) hydrogen atom a, (2) C1-6alkyl, which can have the following substituents: (a) hydroxy, (b) methoxy, (c) cyano, (d) carboxy, (e) halogen, (f) methyl sulphonylamino, (g) C3-8cycloalkyl or phenyl, which can have the following substituents: methyl, halogen, hydroxy or methoxy, (h) thienyl, pyrazolyl, tetrahydropyranyl, thiazolyl, isooxalyl, imidazolyl, tetraazolyl, pyridyl, pyrimidinyl which can have the following substituents: methyl, trifluoromethyl or hydroxy, (3) C2-10alkenyl, (4) C2-10alkynyl, (5) phenyl which can have the following substituents: C1-4alkyl or halogen, or (6) pyridine or tetrahydropyran; R52 is (1) hydrogen atom a, (2) C1-6alkyl which can have the following substituents: (a) hydroxy, (b) methoxy, (c) carboxy, (d) C3-8cycloalkyl, (e) phenyl or (f) oxo, (3) C3-8cycloalkyl or phenyl which can have the following substituents: C1-4alkyl, hydroxy, cyano, oxo, carbamoyl, N-methyl aminocarbonyl, carboxy, halogen, methoxy, trifluoromethoxy, methythio, methylsulphonyl, acetylamino, dimethylamino, acetyl, tetraazolyl, trifluoromethyl or methylsulphonylamino (4) C3-10cycloalkenyl, (5) adamantyl, (6) thienyl, pyrazolyl, tetrahydropyranyl, isoxaazolyl, isothiazolyl, thiadiazolyl, piperidinyl, pyridyl, pyrimidinyl, pyridazinyl, quinolyl, indolyl, benzothiazolyl, benzoisothiazolyl, benzotriazolyl, dioxaindanyl, benzodioxaindanyl which can have the following substituents: C1-4alkyl, hydroxy, oxo, halogen, azido or trifluoromethyl or (7) benzyloxy groups; and R53 is hydrogen atom or C1-6alkyl; to its salts or its solvates. The invention refers also to the regulator CCR5, to the agent of prevention and/or treatment of HIV infection, immunological or inflammatory diseases, to the pharmaceutical composition, to the medicinal preparation, to the method of disease treatment or prevention as well as to the application of compound as in claim 1.

EFFECT: obtaining of new bioactive compounds possessing anti CCR5 receptor activity.

23 cl, 41 ex

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1,4-diazabicyclo[3,2,1]octanecarboxamide with general formula (1) , in which X is a nitrogen atom, P and W each independently represent a nitrogen atom or a group with general formula C-R3, Q and R each independently represent a group with general formula C-R3, R1 is a hydrogen atom, R3 is a hydrogen atom or halogen or C1-C6-alkyl, C1-C6-alkoxy, O-Ms. The invention also relates to a medicinal preparation and pharmaceutical composition based on these compounds for treating or preventing disorders, related to malfunction of nicotinic receptors.

EFFECT: obtaining new compounds and a pharmaceutical composition based on the said compounds, which can be used for treating cognition failure and attention failure, or for treating motor, neurological or alerting symptoms related to dependency on different addictive substances.

5 cl, 2 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to quinobenzoxazin analogues with general formula (1) where V represents H, halo-, or NR1R2; NH2, or NR1-(CR12)n-NR3R4; A represents H, fluoro-, or NR12; Z represents O, S, NR1 or CH2; U represents NR1R2; X represents NR1R2 or halo-; n=1-6; where in NR1R2, R1 and R2 can form 5-7-member heterocyclic ring which is optionally substituted and has 1-2 heteroatoms, selected from group consisting of N, O and S; R1 represents H or C1-6alkyl; R2 represents C1-10alkyl optionally including one or more non-adjacent heteroatoms N or O and is optionally substituted with if necessary substituted 3-6-member carbocyclic or 5-14-member heterocyclic ring; or R2 is 5-14-member heterocyclic ring, which has 1-2 heteroatoms, selected from group consisting of N, O or S, 6-member aryl or 5-7member heteroaryl ring, which contains 1-3 heteroatoms, selected from group consisting of N, O and S, each of which can be, if necessary, substituted; R3 represents H or C1-6alkyl; R4 represents H, C1-6alkyl, optionally substituted with 3-6 carbocyclic or 5-14-member heterocyclic ring, or 6-member aryl, R4 and R3, if necessary, can form optionally 5-7-member substituted heterocyclic ring, which contains 1-2 heteroatoms selected from N and O; W represents substituent, such as described in i.1 of invention formula, where Q, Q1, Q2, and Q3 represents independently CH or N; Y represents independently O or CH; R5 represents substituent in any position of closed ring in form of H or OR2; on condition that U is not morpholinyl or 2,4-difluoroaniline, when X represents F or pyrrolidinyl, A is F, Z represents O, and W represents phenylene; each obligatorily substituted fragment being substituted with one or more halogen, C1-6-alkoxy, amino, carbamate, C1-10alkyl, C2-10alkenyl, each of which is optionally substituted with halogen, =O, 6-member aryl or one or more heteroatom, selected from N and O; 6-member aryl, 3-6-member carbocyclic ring or 5-7-member heterocyclic ring containing 1-2 heteroatoms, selected from group, consisting of N and O; or its pharmaceutically acceptable salts. Invention also relates to pharmaceutical composition based on formula (1) compound and to method of treatment of proliferative cell diseases using formula (1) compounds.

EFFECT: obtaining novel quinobenzoxazin analogues possessing useful biological properties.

48 cl, 3 tbl, 50 ex

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new macrocyclic compounds with formula (I): (where R3, R6, R7 and R21 can be identical or different from each other, and each of them assume values given in the description), their salts used in pharmacology and their hydrate. Compounds with formula (I) are capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, and can be used as therapeutic means of treating solid malignant tumours. The invention also relates to medicinal agents based on these compounds, prevention and treatment method and use of these compounds in making preparations for preventing and treating cancerous diseases.

EFFECT: obtaining compounds, capable of inhibiting angiogenesis, particularly VEGF production in hypoxic conditions, which can be used as therapeutic means of treating solid malignant tumours.

35 cl, 3 tbl, 147 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention pertains to a new piperidine derivative, with the following general formula (I) where R1 - R4 each stands for any of the univalent groups, indicated below: R1 stands for a hydrogen atom, halogen atom, inferior alkyl, which can be substituted with a halogen atom or OH; -O-inferior alkyl, which can be substituted with a halogen atom; -O-aryl, aryl, -C(=O)-inferior alkyl, COOH, -C(=O)-O-inferior alkyl, -C(=O)-NH2, -C(=O)NH-inferior alkyl, -C(=O)N-(inferior alkyl)2, OH, -O-C(=O)-inferior alkyl, NH2, -NH-inferior alkyl, -N-(inferior alkyl)2, NH-C(=O)- inferior alkyl, CN or NO2; R2 and R3 each stands for a hydrogen atom; and R4 stands for any of the univalent groups (a), (b) and (c), shown below in formula 2 where in the above indicated groups (a), (b) and (c), A stands for a pyrrolidine, piperidine, morpholine, piperizine or oxazepane ring; B stands for a pyrrolidine or piperidine ring; R5 and R8-R11 can be identical or different from each other and each stands for a hydrogen atom, -C(=O)-O-inferior alkyl, cycloalkyl or tetrahydropyrane; R6 stands for a hydrogen atom, -C(=O)-O-inferior alkyl, OH, -inferior alkylene-OH or -C(=O)-pyridine; and R7 stands for a hydrogen atom. The invention also pertains to pharmaceutical salts of the piperidine derivative, as well as medicinal compositions.

EFFECT: obtaining new biologically active compounds and a medicinal composition, based on these compounds, which is a sodium channel inhibitor.

10 cl, 91 ex, 22 tbl

FIELD: chemistry.

SUBSTANCE: invention claims compound of the general formula (I) , where R is hydrogen atom or vinyl group; n is 1, X is a group of the formula CH or nitrogen atom, R1 is either phenyl or naphthyl group, or cyclohexyl group, or heteroaryl group, R2 is either hydrogen atom or one or more substitutes selected out of halogen atoms and trifluoromethyl, alkyl, alkoxyl phenyloxy, hydroxyl groups or group of the general formula -NR4R5, SO2NR4R5, or group of the formula -OCF2O-, each of R4 and R5 groups is hydrogen atom or alkyl group; and method of obtaining compound of the general formula (I), medicine, pharmaceutical composition. Compounds display special effect as specific inhibitors of glycine GlyT1 and/or GlyT2 transmitters and thus are applied in treatment of various diseases.

EFFECT: obtaining compounds with high specific inhibition effect.

13 cl, 2 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: derivatives of 7-aryl-3,9-diazabicyclo(3.3.1)non-6-ene of general formula I , general formula I, where X and W or both represent -CH-, or one of them represents -CH-, and the other -N. V represents -A-(CH2)s-, -(CH2)s-A-, -A-(CH2)v-B- or -CH2-A-(CH2)3-B-; A and B represent-O- U -phenyl, possibly 1-3 substituted with halogen, alkyl, alkoxy, CF3, CF3O - or alkylcarbonyl, or pyridyl, monosubstituted with cyanogroup. T represents -CONR1-, -(CH2)pOCO- or -(CH2)pN(R1)CO- Q-alkylene; M - hydrogen, phenyl, possibly substituted, benzo[1,3]dioxol, possibly substituted, or pyridyl; L represents -R3, -COR3, -COOR3, -CONR2R3 or -SO2R3; R1 - hydrogen, alkyl, C3-7 cycloalkyl, pyrrolidinyl, benzo[b]thienyl, chinoxalinyl, phenylalkyl, thienylalkyl or tetrazolylalkyl, possibly substituted. m=1, n=0 or m=0, n=1, p - integer 1-4, s - integer 2-5, v - integer 2-4, optically pure enantiomers, mixtures of enantiomers, pharmaceutically acceptable salts and complexes with solvents, possessing activity of phenin inhibitors.

EFFECT: efficient application in medicine for treatment of cardio-vascular diseases and renal failure.

8 cl, 743 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine-condensed derivatives of formula , where n is selected from 0, 1, 2, 3 and 4, Z1 is selected from N, C(O) and CR3, where R3 represents hydrogen, Z2 is selected from N and CR4, where R4 is selected from hydrogen and halogen, where the bond between Z1 and Z2 is selected from a single bond and a double bond, R1 is selected from C1-C4alkyl and C1-C4alkoxy, R2 is selected from NR5C(O)R6, C(O)NR5R6 and NR5R6, where R5 represents hydrogen, and R6 is selected from hydrogen, C1-C4alkyl and phenyl, where phenyl as R6 is optionally substituted with 1-2 radicals independently selected from a group comprising halogen(C1-C4)alkyl, heteroaryl(C0-C4)alkyl and heterocycloalkyl(C0-C4)alkyl, where any heteroaryl or heterocycloalkyl substitute R6 can be optionally substituted with a substitute independently selected from C1-C4alkyl and heterocycloalkyl, where the said heteroaryl and heterocyclyl represent a saturated or unsaturated 5-6-member ring containing 1 or 2 N atoms as a heteroatom, and to their pharmaceutically acceptable salts, hydrates, solvates and isomers. The invention also relates to a pharmaceutical composition base on a formula I compound and to use of formula I compound for preparing a medicinal agent which can be used for treating diseases or disorders associated with anomalous or disrupted kinase activity, primarily diseases or disorders related to anomalous activation of kinase Ab1, Bcr-Ab1, BMX, BTK, CHK2, c-RAF, CSK, c-SRC, Fes, FGFR3, Flt3, IKKα, IKKβ, JNK2α2, Lck, Met, MKK4, MKK6, MCST2, NEK2, p70S6K, PDGFRβ, PKA, PKBα, PKD2, Rsk1, SAPK2α, SAPK2β, SAPK3, SGK, Tie2 and TrkB.

EFFECT: novel compounds have useful biological properties.

7 cl, 1 tbl, 2 ex

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