Diaminopyrimidine derivatives and methods for production thereof

FIELD: pharmaceutics.

SUBSTANCE: present invention relates to a novel diaminopyrimidine derivative formula 1 or pharmaceutically acceptable salts thereof possessing properties of agonist of 5-HT4 receptors. In formula 1

(Formula 1)

R1 denotes a phenyl group substituted with one or more substitutes selected from a group consisting of hydroxy, amino, halogen, cyano, nitro, C1-5alkyl (where C1-5alkyl is optionally substituted with halogen), C1-5alkoxy, C1-5alkylthio, C1-5alkoxycarbonyl, aminosulphonyl and benzyloxycarbonylamino; or heteroaryl group selected from a group comprising pyridinyl, quinolinyl, chromenonyl, indolyl, indolinyl and benzimidazolyl, wherein heteroaryl group can be optionally substituted with one or more substitutes selected from a group consisting of C1-5alkyl (where C1-5alkyl is optionally substituted with halogen) and acetyl, R2 denotes hydrogen; C1-5alkyl group, optionally substituted with a substitute selected from a group consisting of hydroxy, C1-5alkoxy, benzylamino (where benzylamino is optionally substituted by halogen), phenylamino, C1-5alkylamino, C3-6cycloalkylamino and hydroxy-C1-5alkylamino; C1-5alkoxycarbonyl group or formyl group, R3 denotes hydrogen, hydroxyl group; C1-5alkyl group, optionally substituted with a substitute selected from a group consisting of C1-5alkoxycarbonylamino and di-C1-5alkylamino, or group selected from a group consisting of following formulae A, B, D and E (where symbol * in formulae A, B, D and E denotes position of attachment of said group of compounds of formula 1),

R4 denotes hydrogen, R5 denotes C1-5alkyl group, optionally substituted phenyl or C2-6alkenyl group, optionally substituted phenyl or C3-6cycloalkyl, R6 denotes C1-10alkyl group, optionally substituted with a substitute selected from a group consisting of hydroxy, halogen, C1-5alkoxy, amino, C1-5alkoxycarbonylamino, benzyloxycarbonylamino, di-C1-5alkylamino, C1-5alkoxy-C1-5alkyloxy, phenoxy, benzyloxy, phenyl (where phenyl is optionally substituted with one or more substitutes selected from a group consisting of halogen, amino and C1-5alkoxy), thiophenyl, pyridinyl, piperidinyl, piperazinyl (where piperazinyl is optionally substituted with benzyl) and acetyl; C3-6cycloalkyl group; piperidinyl group; C1-10alkenyl group, optionally substituted phenyl; trifluoromethyl group, trifluoroethyl group or a phenyl group optionally substituted with halogen, R7 denotes hydrogen, R8 and R9 each independently denote hydrogen; C1-10alkyl group, optionally substituted with substitute selected from a group consisting of amino, C1-5alkoxycarbonylamino, hydroxy, C1-5alkylthio, C3-10cycloalkyl, phenyl (where phenyl is optionally substituted with one or more substitutes selected from a group consisting of hydroxy, C1-5alkyl, mono-or di-C1-5alkylamino, trifluoromethyl, halogen, C1-5alkoxy C1-5alkylcarbonyloxy), thiophenyl, pyrrolyl, furanyl (where furanyl is optionally substituted with mono-or di-C1-5alkyl), pyridinyl and benzyloxy; piperidinyl group, optionally substituted benzyl, benzoyl, C1-5alkyl or C1-5alkylcarbonyl; azetidinyl group, optionally substituted C1-5alkoxycarbonyl; C1-5alkylsulphonyl group or C3-10cycloalkyl group.

EFFECT: invention relates to use of formula 1 or its pharmaceutically acceptable salt for preparing a drug for preventing or treating gastrointestinal motility dysfunction; gastrointestinal motor dysfunction is gastroesophageal reflux disease (GERD), lock (constipation), irritable bowel syndrome (IBS), dyspepsia, postoperative intestinal obstruction, prolonged gastric emptying, gastroparesis, intestinal pseudo-obstruction,drug-induced delayed transit content over colon or diabetic gastroparesis.

9 cl, 54 tbl, 495 ex

 



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel heterocyclic compounds of general formula (I) or enantiomers, diastereomers or pharmaceutically acceptable salts thereof, where Y is: phenyl or a heteroaryl selected from thiazolyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl and 1,3,4-thiadiazolyl; wherein the phenyl or heteroaryl is optionally substituted with one substitute selected from fluorine, chlorine, bromine, iodine, C1-4alkyl, trifluoromethyl, C1-4alkoxy, C1-4alkylthio, nitro and cyano; r=1-2; R2 is absent or is an oxo-group; Z is: (a) phenyl substituted with NRaRb; where Ra is: H or C1-4alkyl; where Rb is: C1-4alkyl, cycloalkyl, phenyl, furanylmethyl, or phenyl(C1-2alkyl); and wherein the phenyl or the furanyl are optionally substituted with iodine; alternatively, Ra and Rb are taken together with the nitrogen atom to which they are bonded to form a 5-8 member heterocyclyl, which is optionally condensed to a benzene ring; (b) biphenyl-3-yl or biphenyl-4-yl; where the interior phenyl ring, attached to the carbonyl in formula (I) is optionally substituted with a fluorine atom; and where the terminal phenyl ring is optionally substituted with a substitute selected from trifluoromethyl, C1-4alkoxy, chlorine, dichloro, fluorine, and iodine; (c) phenyl substituted with a substitute selected from C5-8cycloalkyl, -NHC(=O)cyclohexyl, phenyloxy, phenylcarbonyl, phenyl(C1-3)alkyl, phenyl(C1-3)alkoxy, pyrrolyl, pyrazolyl, imidazolyl, isoindol-2-yl-l,3-dione, 2,3-dihydro-isoindol-2-yl; l-(tert- butoxycarbonyl)piperidin-4-yloxy, and 1-(tert-butoxycarbonyl)piperidin-4-yl; (d) phenyl substituted with 1-2 substitutes independently selected from: C1-6alkyl, C1-4alkoxy, iodine, chlorine and nitro; (e) phenyl(C1-2)alkyl; where the phenyl is optionally substituted with 1 or 2 substitutes independently selected from iodine, fluorine, C1-6alkyl, phenyl and NRcRd; where Rc: H or C1-4alkyl; where Rd is: C1-4alkyl or C1-6cycloalkyl(C1-4)alkyl; and where the C1-2alkyl of phenyl(C1-2)alkyl is optionally substituted with phenyl; (f) phenyl(C2-4)alkenyl; where the phenyl is optionally substituted with a substitute selected from C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethylthio and phenyl; (g) naphthyl; where the naphthyl is optionally substituted with one C1-4alkoxy substitute; (h) fluorenyl or xanthenyl; where the fluorenyl or xanthenyl is optionally substituted with an oxo group; (i) C5-8cycloalkyl; where the C5-8cycloalkyl is optionally substituted with one C1-6alkyl substitute; (j) benzene ring-condensed C5-8cycloalkyl or benzene ring-condensed C5-8cycloalkyl(C1-4)alkyl; where said C5-8cycloalkyl fragment is optionally substituted with 1-4 methyl groups; (k) bicyclo[2.2.2]octyl-1-yl; where the bicyclo[2.2.2]octyl-l-yl is optionally substituted with C1-6alkyl; (1) a heteroaryl or benzene ring-condensed heteroaryl selected from benzooxazolyl, quinolinyl, benzimidazolyl, pyridinyl, indolyl, thienyl, furanyl, pyrazolyl, oxazolyl, benzothienyl and benzofuranyl; where the heteroaryl or benzene ring-condensed heteroaryl is optionally substituted with 1 or 2 substitutes independently selected from C1-4alkyl, trifluoromethyl, C5-8cycloalkyl, phenyl, phenyl(C1-2)alkoxy, phenyl(C2-4)alkynyl and dichlorophenoxy; and where the phenyl substitute in the heteroaryl is further optionally substituted with C1-4alkyl, C1-4alkoxy or trifluoromethyl; (m) l,5-diphenyl-lH-pyrazol-3-yl; where the pyrazol-3-yl is optionally substituted with a methyl group; and where each of the phenyl groups of the 1,5-diphenyl substitutes is also optionally substituted with substitutes selected from chlorine, dichloro or aminosulphonyl; (n) 1,2,3,4-tetrahydroquinolin-6-yl; where the 1,2,3,4-tetrahydroquinolin-6-yl is optionally substituted with phenyl or trifluoromethyl-substituted phenyl; and (o) benzene ring-condensed heterocyclyl(C2-4)alkenyl; where the benzene ring-condensed heterocyclyl is attached to the C2-4alkenyl via the benzene ring; and where benzene ring-condensed heterocyclyl is further optionally substituted with C5-6cycloalkyl; taking into account constraining conditions indicated in claim 1. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of producing said pharmaceutical composition, a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds having MGL inhibiting activity.

21 cl, 5 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound, represented by the following formula

,

or its pharmaceutically acceptable salt. In claimed formula each symbol has values, determined in formula of invention. Versions of formula [I] compound and particular compounds are also objects of invention. In addition, invention relates to pharmaceutical composition, ITK inhibitor and means for treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases and methods of treating said diseases.

EFFECT: claimed compounds inhibit induced T-cellular kinase (ITK).

32 cl, 86 tbl, 387 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and their pharmaceutically acceptable salts, wherein A is thiazolyl, oxazolyl, thienyl, furyl, imidazolyl, pyrazolyl or oxadiazolyl (structures of which are presented in cl.1 of the patent claim), R1 represents C1-6alkyl; R2 represents (i) phenyl substituted by halogen; C1-6alkyl optionally substituted by morpholine or C1-6dialkylamino; C1-6alkoxy optionally substituted by halogen; or heterocyclyl, wherein a heterocyclyl substitute is specified in morpholine; pyrazolyl optionally substituted by C1-6alkyl; piperidinyl; pyrrolidinyl; oxadiazolyl substituted by C1-6alkyl; furyl substituted by C1-6alkyl; dioxydoisothiazolidinyl; triazolyl; tetrazolyl substituted by C1-6alkyl, tridiazolyl substituted by C1-6alkyl; thiazolyl substituted by C1-6alkyl; pyridyl; or pyrazinyl; (ii) substituted or unsubstituted heterocyclyl specified in quinolinyl; pyridyl substituted by C1-6alkoxy or morpholinyl; or benzo [d] [1, 2, 3] triazolyl substituted by C1-6alkyl; R3 represents phenyl substituted by 2 or 3 substitutes specified in halogen; C1-6alkyl; C1-6alkoxy optionally substituted by halogen; hydroxy group; cyano; or -C(=O)ORa, wherein Ra represents phenyl; R4 represents hydrogen, C1-6alkyl or C1-6halogenalkyl. The invention also refers to a pharmaceutical composition containing the compounds of formula (I), a method for PDE10 inhibition, a method of treating neurological disorders, and to intermediate compounds: 2-(4-chlor-3,5-dimethoxyphenyl)furan and 4-(5-methyl-1,3,4-thiadiazol-2-yl)benzaldehyde.

EFFECT: compounds of formula (I) as PDE10 inhibitors.

39 cl, 13 ex, 2 tbl, 77 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new chromone derivatives of general formula

,

wherein: R1 represents one or more identical or different substitutes on a benzene ring, each of which independently represents a hydrogen atom, or a halogen atom, or C1-4 alkoxy group, or OH group. or group -O(CH2)nO-, wherein n=1 or 2, R2 represents a hydrogen atom, or C1-4 alkyl group; A and B independently represent either a nitrogen atom, or a carbon atom; R3 represents a hydrogen atom or one or more identical or different substitutes specified in a group consisting of: a halogen atom, C1-4 alkyl group, C1-4 alkoxy group, group -O(CH2)nO-, wherein n=1 or 2, group NO2, group NHSO2R4, group NHR5, OH group, C1-4 halogenoalkyl group, CN group, or R3 makes a ring condensed with a benzene ring bearing it, specified in a group consisting of indole, benzimidazole, carbostyril, benzoxazolone and benzoxazolone and benzimidazolone, R4 represents C1-4 alkyl group, or C1-4 dialkylamino group, or C1-4 alkoxyalkyl group, or C1-4 dialkylaminoalkyl group, R5 represents a hydrogen atom, or C1-4 alkylcarbonyl group, or C1-4 alkoxycarbonyl group, and to its pharmaceutically acceptable salts, as well as to methods for preparing them, and to based pharmaceutical compositions, and to using them as a therapeutic agent for central nervous system disorders, as long as they possess the D3 dopaminergic ligand properties.

EFFECT: preparing the compositions for treating central nervous system disorders, as long as they possess the D3 dopaminergic ligand properties.

17 cl, 1 dwg, 2 tbl, 33 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to pyrazine derivatives of formula I, as well as to their enanthiomers, diastereomers and pharmaceutically acceptable salts, wherein R1 is specified in a group consisting of ii) pyridinyl optionally having one substitute specified in a group consisting of C1-4alkoxy and cyano; and iii) pyrimidin-5-yl; or R1 optionally represents methoxymethyl, when Y represents ethinyl; Y represents ethinyl or a bond; R2 represents phenyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxol-5-yl, indolyl or pyridinyl substituted by methyl, phenyl has one to two substitutes independently specified in a group consisting of C1-4alkyl, C1-4alkoxy, fluorine, chlorine, cyano, cyanomethyl, difluoromethyl, trifluoromethyl and hydroxy; or R2 represents phenyl having one C1-4alkylcarbonylamino or 1H-imidazol-1-yl substitute; X represents O or CH2; L is absent, and R3 represents 4-aminocyclohexyl, or L represents methylene, while R3 is specified in a group consisting of i) pyrrolidin-2-yl; ii) 1-aminoeth-1-yl; and iii) 1-aminocyclopent-1-yl; or R3 is combined into one cycle with L nitrogen atom to which L is attached to form piperazinyl. Besides, the invention refers to specific compounds, a pharmaceutical compound based on a compound of formula I, a method of treating pain and some neurodegenerative diseases.

EFFECT: there are produced new pyrazine derivative effective in treating pain and some neurodegenerative diseases.

21 cl, 3 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to specific compounds or to their therapeutically acceptable salt presented in the patent claim and representing sulphonyl benzamide derivatives. The invention also refers to a pharmaceutical composition inhibiting the activity of anti-apoptotic proteins of the family Bcl-2, containing an excipient and an effective amount of a specific sulphonyl benzamide derivative.

EFFECT: sulphonyl benzamide derivatives inhibiting the activity of anti-apoptotic Bcl-2 proteins.

2 cl, 3 tbl, 558 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new 3-benzofuranylindol-2-one derivatives substituted in position 3 of formula wherein: R1 means a hydrogen atom; R2, R3, R4 equal or different, found in any accessible position of the phenyl ring, means independently a hydrogen atom or a halogen atom; R5 means (C1-6) alkyl group; n means 1; in the form of the base or acid-additive salt, as well as to a therapeutic agent and a pharmaceutical composition based on the above compounds possessing the ghrelin receptor antagonist activity, and to using this compounds for preparing the therapeutic agent for preventing or treating obesity, diabetes, appetite disorders and overweight.

EFFECT: preparing the therapeutic agent used for preventing or treating obesity, diabetes, appetite disorders and overweight.

8 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new 3-benzofuranyl-indol-2-one-3-acetamidopiperazine derivatives of formula

,

wherein: R1 means hydrogen atom; R2, R3, R4 are identical or different, found in any accessible position of phenyl nucleus; they independently mean hydrogen atom and halogen atom; R5 and R6 are identical or different, mean hydrogen atom, (C1-6) alkyl group; R7 means (C1-6) alkyl group; R8 and R9 found in any accessible position of piperazine nucleus, mean hydrogen atom, or (C1-6)alkyl group; at least one of R8 and R9 is differed from H; n means 1; which are present in the form of a base or an acid addition salt, as well as to methods for preparing these compounds, a therapeutic agent or a based pharmaceutical composition for treating obesity, diabetes, appetite disorder and overweight and to therapeutic use of these compounds.

EFFECT: preparing the compounds for treating obesity, diabetes, appetite disorder and overweight and to therapeutic use of these compounds.

10 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention refers to pigment dispersion that can find application in electrophoretic displays. The dispersion contains α) a bis-(oxodihydroindolilene)benzodifuranone colouring agent of formula I wherein R1-R10 have values specified in cl.1, β) a special polymer dispersing agent containing modified poly(meth)acrylates, and γ) a solvent applicable for dispersions used in the electrophoretic displays. There are also described new colouring agents of bis-(oxodihydroindolilene)benzodifuranone compounds, dispersing agents and the electrophoretic display comprising these agents.

EFFECT: presented colouring agents have low conductivity and using them as black pigments in the electrophoretic displays enables reducing energy consumption as compared to using state-of-art carbon black.

11 cl, 1 dwg, 1 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to bis-benzimidazole derivatives of formula I and their optional stereoisomers, pharmaceutically acceptable salts and solvates, wherein R and R' are independently specified in -CR1R2R3, phenyl substituted by 1 substitute specified in halogen; and tetrahydrofuranyl, wherein R1 is specified in C1-4alkyl optionally substituted by methoxy, hydroxyl or dimethylamino; C3-6cycloalkyl; phenyl optionally substituted by 1, 2 or 3 substitutes optionally specified in halogen, C1-4alkoxy, trifluoromethoxy, or 2 substitutes on adjoining atoms of the ring form 1,3-dioxolane group; benzyl substituted by halogen or methoxy; pyridinyl; indolyl; pyridinylmethyl or indolylmethyl; R2 is specified in hydrogen, hydroxyl, di-C1-4alkylamino, (C3-6cycloalkyl) (C1-4alkyl)amino, C1-4alkylcarbonylamino, phenylamino, C1-4alkyloxycarbonylamino, (C1-4alkyloxycarbonyl)(C1-4alkyl)amino, C1-4alkylaminocarbonylamino, tetrahydro-2-oxo-1(2H)-pyrimidinyl, pyrrolidin-1-yl, piperidin-1-yl, 3,3-difluoropiperidin-1-yl, morpholin-1-yl, 7-azabicyclo[2.2.1]hept-7-yl and imidazol-1-yl; and R3 represents hydrogen or C1-4alkyl or CR2R3 together form carbonyl; or CR1R3 form cyclopropyl group. The invention also refers to a pharmaceutical composition based on a compound of formula I.

EFFECT: there are prepared bis-benzimidazole derivatives possessing the inhibitory activity on hepatitis C virus.

9 cl, 4 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel heterocyclic compounds of general formula (I) or enantiomers, diastereomers or pharmaceutically acceptable salts thereof, where Y is: phenyl or a heteroaryl selected from thiazolyl, pyridyl, pyrimidinyl, 1,3,5-triazinyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl and 1,3,4-thiadiazolyl; wherein the phenyl or heteroaryl is optionally substituted with one substitute selected from fluorine, chlorine, bromine, iodine, C1-4alkyl, trifluoromethyl, C1-4alkoxy, C1-4alkylthio, nitro and cyano; r=1-2; R2 is absent or is an oxo-group; Z is: (a) phenyl substituted with NRaRb; where Ra is: H or C1-4alkyl; where Rb is: C1-4alkyl, cycloalkyl, phenyl, furanylmethyl, or phenyl(C1-2alkyl); and wherein the phenyl or the furanyl are optionally substituted with iodine; alternatively, Ra and Rb are taken together with the nitrogen atom to which they are bonded to form a 5-8 member heterocyclyl, which is optionally condensed to a benzene ring; (b) biphenyl-3-yl or biphenyl-4-yl; where the interior phenyl ring, attached to the carbonyl in formula (I) is optionally substituted with a fluorine atom; and where the terminal phenyl ring is optionally substituted with a substitute selected from trifluoromethyl, C1-4alkoxy, chlorine, dichloro, fluorine, and iodine; (c) phenyl substituted with a substitute selected from C5-8cycloalkyl, -NHC(=O)cyclohexyl, phenyloxy, phenylcarbonyl, phenyl(C1-3)alkyl, phenyl(C1-3)alkoxy, pyrrolyl, pyrazolyl, imidazolyl, isoindol-2-yl-l,3-dione, 2,3-dihydro-isoindol-2-yl; l-(tert- butoxycarbonyl)piperidin-4-yloxy, and 1-(tert-butoxycarbonyl)piperidin-4-yl; (d) phenyl substituted with 1-2 substitutes independently selected from: C1-6alkyl, C1-4alkoxy, iodine, chlorine and nitro; (e) phenyl(C1-2)alkyl; where the phenyl is optionally substituted with 1 or 2 substitutes independently selected from iodine, fluorine, C1-6alkyl, phenyl and NRcRd; where Rc: H or C1-4alkyl; where Rd is: C1-4alkyl or C1-6cycloalkyl(C1-4)alkyl; and where the C1-2alkyl of phenyl(C1-2)alkyl is optionally substituted with phenyl; (f) phenyl(C2-4)alkenyl; where the phenyl is optionally substituted with a substitute selected from C1-4alkyl, C1-4alkoxy, trifluoromethyl, trifluoromethylthio and phenyl; (g) naphthyl; where the naphthyl is optionally substituted with one C1-4alkoxy substitute; (h) fluorenyl or xanthenyl; where the fluorenyl or xanthenyl is optionally substituted with an oxo group; (i) C5-8cycloalkyl; where the C5-8cycloalkyl is optionally substituted with one C1-6alkyl substitute; (j) benzene ring-condensed C5-8cycloalkyl or benzene ring-condensed C5-8cycloalkyl(C1-4)alkyl; where said C5-8cycloalkyl fragment is optionally substituted with 1-4 methyl groups; (k) bicyclo[2.2.2]octyl-1-yl; where the bicyclo[2.2.2]octyl-l-yl is optionally substituted with C1-6alkyl; (1) a heteroaryl or benzene ring-condensed heteroaryl selected from benzooxazolyl, quinolinyl, benzimidazolyl, pyridinyl, indolyl, thienyl, furanyl, pyrazolyl, oxazolyl, benzothienyl and benzofuranyl; where the heteroaryl or benzene ring-condensed heteroaryl is optionally substituted with 1 or 2 substitutes independently selected from C1-4alkyl, trifluoromethyl, C5-8cycloalkyl, phenyl, phenyl(C1-2)alkoxy, phenyl(C2-4)alkynyl and dichlorophenoxy; and where the phenyl substitute in the heteroaryl is further optionally substituted with C1-4alkyl, C1-4alkoxy or trifluoromethyl; (m) l,5-diphenyl-lH-pyrazol-3-yl; where the pyrazol-3-yl is optionally substituted with a methyl group; and where each of the phenyl groups of the 1,5-diphenyl substitutes is also optionally substituted with substitutes selected from chlorine, dichloro or aminosulphonyl; (n) 1,2,3,4-tetrahydroquinolin-6-yl; where the 1,2,3,4-tetrahydroquinolin-6-yl is optionally substituted with phenyl or trifluoromethyl-substituted phenyl; and (o) benzene ring-condensed heterocyclyl(C2-4)alkenyl; where the benzene ring-condensed heterocyclyl is attached to the C2-4alkenyl via the benzene ring; and where benzene ring-condensed heterocyclyl is further optionally substituted with C5-6cycloalkyl; taking into account constraining conditions indicated in claim 1. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of producing said pharmaceutical composition, a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel heterocyclic compounds having MGL inhibiting activity.

21 cl, 5 tbl, 11 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound, represented by the following formula

,

or its pharmaceutically acceptable salt. In claimed formula each symbol has values, determined in formula of invention. Versions of formula [I] compound and particular compounds are also objects of invention. In addition, invention relates to pharmaceutical composition, ITK inhibitor and means for treatment or prevention of inflammatory diseases, allergic diseases, autoimmune diseases, transplant rejection and other diseases and methods of treating said diseases.

EFFECT: claimed compounds inhibit induced T-cellular kinase (ITK).

32 cl, 86 tbl, 387 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compounds, which possess an inhibiting activity with respect to anti-apoptotic Bcl-2 proteins. The invention also relates to a pharmaceutical composition, containing the said compounds, and to a method of treating urinary bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukaemia, colorectal cancer, oesophageal cancer, hepatocellular cancer, lymphoblast leukosis, follicular lymphoma, lymphoid malignant diseases of a T-cell or B-cell origin, melanoma, myelogenous leukaemia, myeloma, oral cavity cancer, ovarian cancer, non-small cell lung cancer, prostate cancer, small-cell lung cancer or spleen cancer.

EFFECT: obtaining the compounds, possessing the inhibiting activity with respect to anti-apoptotic Bcl-2 proteins.

4 cl, 5 tbl, 405 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing carbonyl derivatives of 5,10,15,20-tetraphenylporphyrin of formula I where R is o-carborane or m-carborane, which are obtained by reacting mercaptocarborane with 5,10,15,20-tetra(n-trifluoromethanesulphonylmethyloxyphenyl)porphyrin in palladium catalysis conditions while boiling in anhydrous toluene while stirring in an atmosphere of an inert gas at room temperature. The method includes successively adding diisopropylethylamine (DIPEA), the corresponding mercaptocarborane, 1,1'-bis(diphenyl-phosphino)ferrocene (dppf) and tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), followed by boiling the reaction mixture in an Ar atmosphere for a few hours, separating the finished products using know techniques; 5,10,15,20-tetra(n-trifluoromethanesulphonylmethyloxyphenyl)porphyrin is obtained by reacting 5,10,15,20-tetrahydroxyporphyrin with a trifluoromethanesulphonic acid anhydride in a medium of methylene chloride in an atmosphere of an inert gas.

EFFECT: obtaining novel carbonyl derivatives of 5,10,15,20-tetraphenylporphyrin, which can be used as anti-tumour agents in boron neutron capture therapy and photodynamic therapy of cancerous diseases.

1 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula , wherein Y and Z are independently specified in a group of a) or b) so that one of Y or Z is specified in the group a), and another one - in the group b); the group a) represents i) substituted C6-10aryl; ii) C3-8cycloalkyl; iii) trifluoromethyl or iv) heteroaryl specified in a group consisting of thienyl, furanyl, thiazolyl, isothiazolyl, oxazolyl, pyrrolyl, pyridinyl, isoxazolyl, imidazolyl, furasan-3-yl, benzothienyl, thieno[3,2-b]thiophen-2-yl, pyrazolyl, triazolyl, tetrazolyl and [1,2,3]thiadiazolyl; the group b) represents i) C6-10aryl; ii) heteroaryl specified in a group consisting of thiazolyl, pyridinyl, indolyl, pyrrolyl, benzoxazolyl, benzothiazolyl, benzothienyl, benzofuranyl, imidazo[1,2-a]pyridin-2-yl, furo[2,3-b]pyridinyl, pyrrolo[2,3-b]pyridinyl, pyrrolo[3,2-b]pyridinyl, thieno[2,3-b]pyridinyl, quinolinyl, quinazolinyl, thienyl and benzimidazolyl; iii) benzofused heterocyclyl attached through a carbon atom, and when a heterocyclyl component contains a nitrogen atom, the carbon atom is optionally substituted by one substitute specified in a group consisting of C3-7cycloalkylcarbonyl; C3-7cycloalkylsulphonyl; phenyl; phenylcarbonyl; pyrrolylcarbonyl; phenylsulphonyl; phenyl(C1-4)alkyl; C1-6alkylcarbonyl; C1-6alkylsulphonyl; pyrimidinyl and pyridinyl; C3-7cycloalkylcarbonyl, phenyl, phenylcarbonyl, phenyl(C1-4)alkyl and phenylsulphonyl are optionally substituted by trifluoromethyl, or by one or two fluor-substitutes; iv) phenoxatiynyl; vi) fluoren-9-on-2-yl; vii) 9,9-dimethyl-9H-fluorenyl; viii) 1-chlornaphtho[2,1-b]thiophen-2-yl; ix) xanthen-9-on-3-yl; x) 9-methyl-9H-carbazol-3-yl; xi) 6,7,8,9-tetrahydro-5H-carbazol-3-yl; xiii) 3-methyl-2-phenyl-4-oxochromen-8-yl; or xiv) 1,3-dihydrobenzimidazol-2-on-5-yl optionally substituted by 1-phenyl, 1-(2,2,2-trifluoroethyl), 1-(3,3,3-trifluoropropyl) or 1-(4,4-difluorocyclohexyl); 1-phenyl is optionally substituted by one or more fluor-substitutes or trifluoromethyl; or xv) 4-(3-chlorophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl; R1 represents C6-10aryl, C1-3alkyl, benzyloxymethyl, hydroxy(C1-3)alkyl, aminocarbonyl, carboxy, trifluoromethyl, spirofused cyclopropyl, 3-oxo or aryl(C1-3)alkyl; or when s is equal to 2 and R1 represents C1-3alkyl, the substitutes C1-3akyl is taken with a piperazine ring to form 3,8-diazabicyclo[3.2.1]octanyl or 2,5-diazabicyclo[2.2.2]octanyl ring system, and its pharmaceutical compositions.

EFFECT: preparing the new pharmaceutical compositions.

20 cl, 7 tbl, 72 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula:

,

wherein: each D and Z is independently absent or represents an optionally substituted linear aliphatic group containing zero to eight carbons, wherein 'aliphatic' refers to an alkyl, alkenyl or alkynyl group, and 'optionally substituted' refers to substituting by replacing independently one, two or more hydrogen atoms by substitutes specified in -F, -Cl, -Br, -I, -OH, -NO2, -N3, -CN, -NH2, -NH-C1-C12-alkyl, -NH-C2-C8-alkenyl, -NH-C2-C8-alkynyl, -NH-C3-C12-cycloalkyl, -dialkylamino, -O-C1-C12-alkyl, -NHC(O)-C1-C12-alkyl, -NHC(O)-C2-C8-alkenyl, -NHC(O)-C2-C8-alkynyl, -NHC(O)-C3-C12-cycloalkyl; each A and E is independently absent or represents a cyclic group with the above cyclic group is independently specified in a group consisting of aryl or heteroaryl, each of which is optionally substituted; 'aryl' refers to phenyl, naphthyl, tetrahydronaphthyl, indanyl or idenyl; 'heteroaryl' refers to pyridinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, thiophenyl, furanyl, quinolinyl, isoquinolinyl, benzimidazolyl, benzoxazolyl or quinoxalinyl; 'optionally substituted' refers to substituting by replacing independently one, two, three or more hydrogen atoms by substitutes specified by -F, -Cl, -Br, -I, -OH, -NO2, -N3, -CN, -NH2, -NH-C1-C12-alkyl, -NH-C2-C8-alkenyl, -NH-C2-C8-alkynyl, -NH-C3-C12-cycloalkyl, -dialkylamino, -O-C1-C12-alkyl, -NHC(O)-C1-C12-alkyl, -NHC(O)-C2-C8-alkenyl, -NHC(O)-C2-C8-alkynyl, -NHC(O)-C3-C12-cycloalkyl; T is absent or represents an optionally substituted aliphatic group containing 1 to 24 carbons; 'aliphatic' refers to an alkyl, alkenyl or alkynyl group; 'optionally substituted' refers to substituting substituting by replacing independently one, two, three or more hydrogen atoms by substitutes specified in -F, -Cl, -Br, -I, -OH, -NO2, -N3, -CN, -NH2, -NH-C1-C12-alkyl, -NH-C2-C8-alkenyl, -NH-C2-C8-alkynyl, -NH-C3-C12-cycloalkyl, -dialkylamino, -O-C1-C12-alkyl, -NHC(O)-C1-C12-alkyl, -NHC(O)-C2-C8-alkenyl, -NHC(O)-C2-C8-alkynyl, -NHC(O)-C3-C12-cycloalkyl; one to four of A, D, E, T and Z are absent; the ring B is specified in imidazolyl, pyrazolyl, 1,3,4-thiazolyl, and 1,3,4-oxadiazolyl, and the ring B is bound to J through atom C and bound to Z, E, T, A and D through atom C; in each specific case, R1 is independently specified in a group consisting of hydrogen, halogen, cyano optionally substituted by C1-C4alkyl, -O-R11, -NRaRb, -C(O)R11, -CO2R11 and -C(O)NRaRb; in each specific case, R11 independently represents hydrogen or optionally substituted C1-C8alkyl; in each specific case, each Ra and Rb are independently specified in hydrogen, C1-C8alkyl and C2-C8alkenyl; u is independently equal to 1, 2 or 3; Q and J represent R6 is specified in a group consisting of -C(O)-R12, -C(O)-C(O)-R12, -S(O)2-R12, and -C(S)-R12; in each specific case, R12 is independently specified in a group consisting of -O-R11, -NRaRb, and -R13; and in each specific case, R13 is independently specified in a group consisting of: hydrogen, C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C3-C8cycloalkyl and C3-C8cycloalkenyl, each of which is optionally substituted; 'optionally substituted' refers to substituting independently by replacing one, two, three or more hydrogen atoms by substitutes specified in -F, -Cl, -Br, -I, -OH, -NO2, -N3, -CN, -NH2, -NH-C1-C12-alkyl, -NH-C2-C8-alkenyl, -NH-C2-C8-alkynyl, -NH-C3-C12-cycloalkyl, -dialkylamino, -O-C1-C12-alkyl, -NHC(O)-C1-C12-alkyl, -NHC(O)-C2-C8-alkenyl, -NHC(O)-C2-C8-alkynyl, -NHC(O)-C3-C12-cycloalkyl, which inhibit an RNA-containing virus, particularly hepatitis C virus (HCV).

EFFECT: preparing hepatitis C inhibitors.

38 cl, 22 tbl, 516 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to pyrazine derivatives of formula I, as well as to their enanthiomers, diastereomers and pharmaceutically acceptable salts, wherein R1 is specified in a group consisting of ii) pyridinyl optionally having one substitute specified in a group consisting of C1-4alkoxy and cyano; and iii) pyrimidin-5-yl; or R1 optionally represents methoxymethyl, when Y represents ethinyl; Y represents ethinyl or a bond; R2 represents phenyl, benzofuranyl, 2,3-dihydrobenzofuranyl, benzo[1,3]dioxol-5-yl, indolyl or pyridinyl substituted by methyl, phenyl has one to two substitutes independently specified in a group consisting of C1-4alkyl, C1-4alkoxy, fluorine, chlorine, cyano, cyanomethyl, difluoromethyl, trifluoromethyl and hydroxy; or R2 represents phenyl having one C1-4alkylcarbonylamino or 1H-imidazol-1-yl substitute; X represents O or CH2; L is absent, and R3 represents 4-aminocyclohexyl, or L represents methylene, while R3 is specified in a group consisting of i) pyrrolidin-2-yl; ii) 1-aminoeth-1-yl; and iii) 1-aminocyclopent-1-yl; or R3 is combined into one cycle with L nitrogen atom to which L is attached to form piperazinyl. Besides, the invention refers to specific compounds, a pharmaceutical compound based on a compound of formula I, a method of treating pain and some neurodegenerative diseases.

EFFECT: there are produced new pyrazine derivative effective in treating pain and some neurodegenerative diseases.

21 cl, 3 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to specific compounds or to their therapeutically acceptable salt presented in the patent claim and representing sulphonyl benzamide derivatives. The invention also refers to a pharmaceutical composition inhibiting the activity of anti-apoptotic proteins of the family Bcl-2, containing an excipient and an effective amount of a specific sulphonyl benzamide derivative.

EFFECT: sulphonyl benzamide derivatives inhibiting the activity of anti-apoptotic Bcl-2 proteins.

2 cl, 3 tbl, 558 ex

FIELD: medicine.

SUBSTANCE: present invention refers to compounds having formula III such as below, wherein: Q represents C(Y3) or N; R represents H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 represents heteroaryl or heterocyclyl each of which is optionally substituted by one or more C1-6alkyls, hydroxyC1-6alkyls, oxogroups or halogenC1-6alkyls; R2 represents -C(=O), -O, -C(R2')2, -C(R2')2C(=O), -C(R2')2C(=O)NR2', C(R2')2 N(R2')C(=O), -C(=NH), -C(R2')2NR2' or -S(=O)2; each R2' independently represents H or C1-6alkyl; R3 represents H or R4; R4 represents C1-6alkyl, C1-6alkoxygroup, aminogroup, C1-6alkylaminogroup, di(C1-6alkyl)aminogroup, heterocyclyl, C1-10alkylheterocycloalkyl, heterocycloalkylC1-10alkyl each of which is optionally substituted by one or more C1-6alkyls, C1-6alkylaminogroups, di(C1-6alkyl)aminogroups, hydroxygroups, hydroxyC1-6alkyls, C1-6alkoxygroups, oxogroups or halogenC1-6alkyls; X represents CH; X' represents CH; and the rest symbols have values as specified in the patent claim. The compounds of formula III inhibit Bruton's tyrosine kinase (Btk). There are also described compositions containing the compounds of formula III, and at least one carrier, thinner or excipient, and a method for producing the compound of formula X in accordance with the following procedure.

EFFECT: compositions are effective for modulating Btk activity and treating diseases related to Btk hyperactivity, and can be used for treating inflammatory and autoimmune diseases related to disturbed B-cell proliferation, such as rheumatoid arthritis.

22 cl, 2 tbl, 260 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to bis-benzimidazole derivatives of formula I and their optional stereoisomers, pharmaceutically acceptable salts and solvates, wherein R and R' are independently specified in -CR1R2R3, phenyl substituted by 1 substitute specified in halogen; and tetrahydrofuranyl, wherein R1 is specified in C1-4alkyl optionally substituted by methoxy, hydroxyl or dimethylamino; C3-6cycloalkyl; phenyl optionally substituted by 1, 2 or 3 substitutes optionally specified in halogen, C1-4alkoxy, trifluoromethoxy, or 2 substitutes on adjoining atoms of the ring form 1,3-dioxolane group; benzyl substituted by halogen or methoxy; pyridinyl; indolyl; pyridinylmethyl or indolylmethyl; R2 is specified in hydrogen, hydroxyl, di-C1-4alkylamino, (C3-6cycloalkyl) (C1-4alkyl)amino, C1-4alkylcarbonylamino, phenylamino, C1-4alkyloxycarbonylamino, (C1-4alkyloxycarbonyl)(C1-4alkyl)amino, C1-4alkylaminocarbonylamino, tetrahydro-2-oxo-1(2H)-pyrimidinyl, pyrrolidin-1-yl, piperidin-1-yl, 3,3-difluoropiperidin-1-yl, morpholin-1-yl, 7-azabicyclo[2.2.1]hept-7-yl and imidazol-1-yl; and R3 represents hydrogen or C1-4alkyl or CR2R3 together form carbonyl; or CR1R3 form cyclopropyl group. The invention also refers to a pharmaceutical composition based on a compound of formula I.

EFFECT: there are prepared bis-benzimidazole derivatives possessing the inhibitory activity on hepatitis C virus.

9 cl, 4 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to benzimidazole-4-carboxamide derivatives of formula , wherein X means an alkenyl group C2-C7 substituted by two methyls, nitro-radical mono-substituted thienyl, unsubstituted quinolinyl, unsubstituted indolyl, unsubstituted pyridazinyl, unsubstituted piperazinyl, C1-C6-alkyl disubstituted piperazinyl, unsubstituted piperidinyl, unsubstituted pyrazinyl, unsubstituted imidazolyl, unsubstituted pyrimidinyl, phenyl monosubstituted pyrimidinyl, pyrimidinyl disubstituted by an amine radical and a radical specified in a group containing -F, -Cl, -Br or -I, hydroxyl trisubstituted phenyl, methoxy-radical trisubstituted phenyl, hydroxyl and methoxy-radical disubstituted phenyl, pyrazolyl disubstituted by a radical specified in a group containing a C1-C6-alkyl, and by a radical specified in a group containing -F, -C1, -Br or -I; Y means aminophenyl monosubstituted by a radical of -F, -O, -Br or -I phenyl, hydroxyethyl disubstituted by hydroxymethyl or C1-C6-alkyl and phenyl monosubstituted by a nitro group, an amino group or a halogen atom; Y also means unsubstituted piperazinyl, unsubstituted pyridyl, unsubstituted pyrazinyl, C1-C6-alkyl monosubstituted thiazol, unsubstituted pyrimidinyl, unsubstituted purinyl. The invention also refers to a pharmaceutical composition based on the compound of formula (I), using the compound of formula (I), a method for producing the compound of formula (I).

EFFECT: there are prepared new benzimidazol-4-carboxamide derivatives possessing antiviral activity.

5 cl, 6 dwg, 4 tbl, 688 ex

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