2-aminopyrasine derivatives as csf-1r kinase inhibitors

FIELD: pharmacology.

SUBSTANCE: invention relates to a compound that is an amino acid or ester of an amino acid of formula , or a pharmaceutically acceptable salt thereof, which has an inhibitory activity against CSF-1R kinase. In formula (I), ring A is a phenyl group; R1 and R2 independently represent a hydrogen atom, a halogen atom or an unsubstituted C1-4 alkyl; n is 1; X is NH; V is -N=, W is -C(Z)=; Z represents a hydrogen atom, a fluorine atom, a chlorine atom or unsubstituted C1-3 alkyl; ring B is a 1,4-phenylene, 1,3-phenylene or pyridinyl group; [Linker] is a -(CH2)m-X1-(Alk1)x-Y1 group, where m is 0, 1, 2 or 3; x is 0 or 1; Alk1 is an unsubstituted C1-3 alkylene group; X1 and Y1 independently represent a bond, -O-, -S-, -NR7th-, -C(=O) - or -C(=O)NR5-, where R5 is a hydrogen atom or C1-4 alkyl and R7 is a hydrogen atom, unsubstituted C1-4 alkyl or -C(=O)CH3; R is a group of formula or , in which R8 is a -COOH group or an ester group of the formula -(C=O)OR14, where R14 is R15R16R17C-, where any R15 represents a hydrogen atom or C1-3alkyl-(Z1)a-[(C1-C3)alkyl]b-, where a and b are independently 0 or 1, Z1 is -O-, -S- or -NH-, R16 and R17 independently represent a hydrogen atom or C1-3 alkyl- or R15 and R16, taken together with the carbon atom to which they are attached, form a 3-7-membered cycloalkyl ring; and R17 represents a hydrogen atom; where (i) R9 and R10 are side chains of natural amino acids, (ii) one of R9 and R10 represents a hydrogen atom or unsubstituted C1-4 alkyl, and the other is an unsubstituted C1-6 alkyl group or C1-6 alkyl group substituted by a C1-4 alkoxy group, or (iii) R9 and R10, taken together with the carbon atom to which they are attached, form a saturated spiro-cyclobutyl ring; R11 represents a hydrogen atom or an unsubstituted C1-2alkyl group; ring D is a 5- to 7-membered saturated heterocyclyl group with at least one nitrogen atom in the ring. The invention also relates to a pharmaceutical composition, a method of treatment or prevention of diseases or disorders mediated by CSF-1R kinase, as well as application of the said compounds for preparation of a medicament useful for treatment of such diseases.

EFFECT: increased application efficiency.

18 cl, 59 ex

 



 

Same patents:

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

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: chemistry.

SUBSTANCE: invention relates to a concentrated storage-stable aqueous solution (S) comprising components (a), (b) and (c), wherein component (a) is at least one optical brightening agent of formula (1), in which the anionic charge on the brightener is balanced by a cationic charge composed of one or more cations selected from a group consisting of hydrogen, alkali metal cation, alkali-earth metal cation, ammonium, ammonium which is mono-, di- or trisubstituted by a C1-4 linear or branched alkyl radical and ammonium which is mono-, di- or trisubstituted by a C1-4 linear or branched hydroxyalkyl radical, and the concentration of component (a) is 0.08-0.3 mol/kg, based on the total weight of the concentrated storage-stable aqueous solution (S); component (b) is at least one inorganic salt (SA), in a concentration of 2-15 wt %, based on the total weight of the concentrated storage-stable aqueous solution (S), where the salts (SA) are preferably by-products of the production process and component (c) is water, in a concentration of 10-88 wt %, based on the total weight of the concentrated storage-stable aqueous solution (S).

EFFECT: invention relates to a method of producing a concentrated storage-stable aqueous solution (S), a method for use thereof as an optical brightening agent for bleaching cellulose substrates, fabrics or nonwoven materials, a sizing solution or suspension when processing paper and a pigmented coating composition containing the solution (S).

23 cl, 1 dwg, 7 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely, to novel heterocyclic compounds of the general formula or to their pharmaceutically acceptable salts, where R1 stands for cyano, nitro, amino, -NHCOOR4 or -NHCOR4; R2 stands for a halogen, C1-alkyl, halogenC1-alkyl or C1-alkoxy; R3 stands for C1-alkyl; or both radicals R3 form a cycloalkyl, containing 3 members, together with carbon atom, which they are bound to; X stands for either an alkylene chain of 4-7 carbon atoms, linear or branched, and the said chain can contain one or several similar or different additional units, selected from -O-, -N(R5)-; either a group where n1 and p1 stand for two integer numbers, the sum of which n1+p1 is an integer number, selected from 2; R6 and R7 together form a covalent bond or R6 and R7 together with carbon atoms, which they are bound to, form a cycle or a cycloalkyl, containing 3 members; R4 stands for C1-alkyl; R5 stands for C1-alkyl. The invention also relates to particular compounds, a pharmaceutical composition based on formula (I), application of the formula (I) compound.

EFFECT: obtained are the novel heterocyclic compounds, useful in treating cancer.

23 cl, 10 dwg, 23 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

possessing properties of binding with delta opioid receptors. In formula I R1 is selected from the group, consisting of phenyl, pyridinyl and thiazolyl, with R1 being optionally substituted with one or two substituents, independently selected from the group, consisting of C1-4alkoxy, fluorine atom, chlorine atom, bromine atom and cyanogroup; in addition, R1 is optionally substituted with di(C1-4alkyl)aminocarbonyl; Y represents O, S, H3, vinyl, ethinyl or S(O); R2 represents a substituent, selected from the group, consisting of hydrogen, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, fluorine atom, chlorine atom, bromine atom and hydroxy; Ra represents hydrogen or methyl; R3 is selected from the group, consisting of pyrrolidin-2-ylmethyl; pyrrolidin-3-ylmethyl; piperidin-2-ylmethyl, piperidin-3-ylmethyl, piperidin-4-ylmethyl, piperidin-2-ylethyl, piperidin-3-ylethyl, piperidin-4-ylethyl, pyridine-4-yl-(C1-2)alkyl, azetidin-3-ylmethyl; morpholin-2-ylmethyl, morpholin-3-ylmethyl, imidazolylmethyl, thiazolylmethyl, (amino)-C3-6cycloalkyl, 3-hydroxy-2-aminopropyl, 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.2]octanyl, guanidinylethyl, 4-(imidazol-1-yl)phenylmethyl, 2-(methylamino)ethyl, 2-diethylaminoethyl, 4-diethylaminobut-2-yl, piperidin-3-yl, piperidin-4-yl and pyrrolidin-3-yl; with piperidin-3-yl being optionally substituted on a carbon atom with phenyl; with pyrrolidin-2-yl in pyrrolidin-2-yl-methyl, pyrrolidin-3-yl, piperidin-3-yl and piperidin-4-yl being optionally substituted on a nitrogen atom with methyl, phenylmethyl, phenethyl or methylcarbonyl.

EFFECT: compounds can be used in the treatment of pain, induced by diseases or conditions, such as osteoarthritis, rheumatoid arthritis, migraine, burn, fibromyalgia, cystitis, rhinitis, neuropathic pain, idiopathic neuralgia, toothache, etc.

24 cl, 3 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing pyrazoline carboxamidine derivatives of formula . Said compounds are known as powerful 5-HT6 antagonists. The disclosed method comprises reacting a corresponding substituted 4,5-dihydro-(1H)-pyrazole or an isomer thereof with isothiocyanate R6-N=C=S to obtain an amide of substituted 4,5-dihydro-(1H)-pyrazole-1-carbothioic acid or tautomeric substituted 4,5-dihydro-(1H)-pyrazole-1-carboxymidothioic acid . The obtained intermediate compounds are reacted with a corresponding alkylating agent to obtain an intermediate S-alkylated compound . Said intermediate compound is reacted with a sulphonamide derivative R7SO2NH2 and the target compound of formula (I) is separated from the reaction mixture. The invention also relates to novel intermediate products (IIIa), (IIIb) and (IV). Symbols given in the formulae have values given in the description.

EFFECT: providing an alternative method which improves atom efficiency of synthesis of desired compounds with higher output compared to existing methods for synthesis of said compounds.

8 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, namely to compounds of formula (I), wherein R1 and R2 independently represent C6-C10 aryl optionally substituted by -OH, halogen, -OC1-C3 alkyl, -NO2, -CF3 or C1-C3 alkyl, or 5- or 6-merous heteroaryl containing one heteroatom specified in N, S and O; A and M independently represent a methylene group or a single bond; an adjacent aromatic cycle is attached directly to an amide group; the group Y=Z represents together and irregularly oxygen atom (-O-), cis-vinylidene group (-CH=CH-), iminogroup (-N=CH- or -CH=N-) or methylene group with sp2-hybridised carbon atom (=CH-); X irregularly represents methine group (=CH-), cis-vinylidene group (-CH=CH-) or carbon atom (=N-), and W represents hydroxyl group (-OH), C1-C6 alkyl optionally substituted by -SH, 5- or 6-merous heteroaryl containing 1 to 2 nitrogen heteroatoms, or C6-C10 aryl, optionally substituted by -SH, -NH2, and their pharmaceutically acceptable salts.

EFFECT: described are the methods for preparing the compounds, using as a drug for treating cancer and the based pharmaceutical composition.

14 cl, 6 tbl, 49 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: chemistry.

SUBSTANCE: invention relates to a novel crystalline form of N-[-2[[(2,3-difluorophenyl)methyl]thio]-6-{[(1R,2S)-2,3-dihydroxy-1-methylpropyl]oxy}-4-pyrimidinyl]-1-azatidine-sulphonamide, which has an X-ray powder diffractogram, measured with the application of a wavelength of X-rays of 1.5418 E and containing, at least, one crystalline peak with a value 2-theta (in degrees) 21.0, 28.8 and/or 29.1; or containing, at least, 2 crystalline peaks with a value 2-theta (in degrees) 21.0, 28.8 and/or 29.1; or containing, at least, 3 crystalline peaks with a value 2-theta (in degrees) 21.0, 28.8 and/or 29.1. The said crystalline form can contain additional crystalline peaks with a value 2-theta (in degrees), selected from 12.9 and 18.0, obtained under the said conditions.

EFFECT: crystalline form has the X-ray powder diffractogram, measured with the application of a wavelength of X-rays of 1,5418 E, with the crystalline peaks with a value 2-theta (in degrees) 12,9, 13,1, 18,0, 21,0, 22,5, 25,1, 25,3, 28,8, 29,1 and 30,4, and has melting point (beginning) 152,7°C.

6 cl, 3 dwg, 2 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new aminotetraline derivatives of formula (I) and their physiologically tolerable salts. In formula

,

A means a benzene ring or a ring specified in a group consisting of a 5-merous ring

,

R means the group R1-W-A1-Q-Y-A2-X1-; R1 means hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl-C1-C4-alkyl, halogenated C1-C6-alkyl, tri-(C1-C4-alkyl)-silyl-C1-C4-alkyl, C1-C6-alkoxy-C1-C4-alkyl, amino-C1-C4-alkyl, C3-C6-cycloalkyl, C2-C6-alkenyl, an optionally substituted phenyl, C1-C6-alkoxy, di-C1-C6-alkylamino, an optionally substituted 5 or 6-merous heterocyclyl containing 1-3 heteroatoms specified in nitrogen and/or oxygen or sulphur; W means a bond; A1 means a bond; Q means -S(O)2- or -C(O)-; Y means -NR9- or a bond; A2 means C1-C4-alkylene, or a bond; X1 means -O-, C1-C4-alkylene, C2-C4-alkynylene; R2 means hydrogen, halogen, or two radicals R2 together with the ring atom to which they are attached form a benzene ring; R3 means hydrogen. The other radical values are specified in the patent claim. The invention also refers to intermediate products for preparing the compounds of formula (I).

EFFECT: compounds possess the properties of glycine transporter inhibitors, particularly GlyT1 and can find application in treating neurological and psychiatric disorders, such as dementia, bipolar disorder, schizophrenia, etc or for managing pain related to glycerinergic or glutamatergic neurotransmission dysfunction.

20 cl, 2 tbl, 326 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing compounds of formula where R1a and R1b are selected from H and F and one of R1a and R1b is F, Het is tetrazolyl, optionally substituted with methyl, R2 is selected from benzyl and C1-C6 alkyl, optionally substituted with a halogen or C1-C4 alkyloxy. The present method includes combining compounds and where X is selected from Cl, Br, I and trifluoromethanesulphonate, Y is selected from BF3 and BR3R4, R3 and R4 are selected from OH, C1-C6monoalcohols and C1-C6diatomic alcohols, or where R3 and R4 together with B, to which they are attached, form a cyclic boronate optionally substituted with methyl.

EFFECT: obtaining oxazolidinones.

22 cl, 10 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of structural formula (I), which possess the properties of HCV polymerase inhibitors. In formula , is specified in a group consisting of a single carbon-carbon bond and a double carbon-carbon bond; R1 and R3 are specified in hydrogen and methyl; R2 represents hydrogen; R5 is specified in a group consisting of hydrogen, hydroxy, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, C2-C6alkenyloxy, C3-C6alkynyloxy and halo; L represents a bond, and R6 represents a condensed 2-ring carbocyclyl, wherein each substitute is optionally substituted by one or more substitutes independently specified in a group consisting of RE, RF, RG, RH, RI, RJ and RK; or L is specified in a group consisting of a bond, C≡C, C(O)N(RC), N(RD)C(O), C1-C2-alkylene, C(H)2O, OC(H)2, cyclopropyl-1,2-ene, C(H)2N(RL), N(RM)C(H)2, C(O)CH2 and CH2C(O), and R6 is specified in a group consisting of C5-C6-carbocyclyk and 5-6-merous heterocyclyl, wherein each substitute is optionally substituted by one or more substitutes independently specified in a group consisting of RE, RF, RG, RH, RI, RJ, RK, RL and RM; the R4, RE, RF, RG, RH, RI, RJ, RK, RL and RM values are presented in the patent claim.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, to using the compounds for producing a drug preparation for HCV RNA polymerase inhibition and hepatitis C treatment, and to a method for preparing the above compounds.

21 cl, 46 dwg, 42 tbl, 140 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of structural formula I, their pharmaceutically acceptable salts and crystalline forms, which possess the properties of HCV polymerase inhibitor. In formula I is specified in a group consisting of a single carbon-carbon bond and a double carbon-carbon bond; R1 represents hydrogen; R2 is specified in a group consisting of hydrogen and halo; R3 represents hydrogen; R4 is specified in a group consisting of halo, C1-C6alkyl, C1-C6alkylsulphonyl and 5-6-merous heteroaryl containing heteroatom specified in N, O and S, wherein alkyl is optionally substituted by one or more hydroxy; R5 is specified in a group consisting of hygrogen, hydroxy, C1-C6alkyloxy and halo; L is specified in a group consisting of C(RA)=C(RB), ethylene and cyclopropyl-1,2-ene; RA and RB are independently specified in a group consisting of hydrogen, C1-C6alkyl, C1-C6alkyloxy and halo; R6 represents C6aryl optionally substituted by one or more substitutes independently specified in a group consisting of RE, RF, RG, RH, RI and RJ; the substitutes RE, RF, RG, RH, RI and RJ are presented in the patent claim.

EFFECT: invention refers to the pharmaceutical composition containing the above compounds, to using the compounds for inhibiting HCV RNA-polymerase and treating hepatitis C and to a method of preparing the above compounds.

40 cl, 23 dwg, 7 tbl, 40 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pyrimidine derivatives of structural formula (I-L0) and their crystalline forms possessing the inhibitory activity on the hepatitis C virus (HCV) polymerase. In formula is specified in a single or double carbon-carbon bond; R1, R2 and R3 represent hydrogen; R4 is specified in halo, C1-C6alkyl, C2-C6alkinyl, amino, C1-C6alkylsulphonyl, C3-C10carbocyclyl and 5-6-merous heterocyclyl having a heteroatom specified in a group consisting of O and S, wherein amino is optionally substituted by one or two C1-C6alkylsulphonyls, and C1-C6alkyl and C2-C6alkynyl are optionally substituted by one or more substitutes optionally specified in a group consisting of halo, oxo, hydroxy, C1-C6alkyloxy and trimethylsilyl, and C3-C10carbocyclyl and 5-6-merous heterocyclyl are optionally substituted by substitutes specified in C1-C6alkyl, halo and amino, wherein amino is optionally substituted by one or two C1-C6alkylsulphonyls; R5 is specified in a group consisting of hydrogen, hydroxy, C1-C6alkyloxy and halo; R6 represents a condensed 2-ring C3-C10carbocyclyl optionally substituted by substitutes specified in RE, RF, RG, RH, RI, RJ and RK, the values of which are specified in the patent claim.

EFFECT: invention refers to a pharmaceutical composition containing the above compounds, to using the compounds for producing a therapeutic agent for hepatitis C, to an intermediate compound for producing the compound of structural formula (I-L0) and to a method for preparing the above compounds and their crystalline forms.

70 cl, 23 dwg, 9 tbl, 83 ex

FIELD: chemistry.

SUBSTANCE: invention relates to heterocyclic compound of formula or to its pharmaceutically acceptable salt, where Alk represents linear C1-6 alkylene group, branched C1-6 alkylene group or C1-6 alkylene group, which has ring structure, where part of carbon atoms, constituting ring structure can be optionally substituted with oxygen atom, in ring X, X1 represents N or CRX1, X2 represents N or CRX2, X3 represents CRX3, X4 represents N or CRX4, where RX1, RX2, RX3 and RX4 each independently represents hydrogen atom; linear or branched C1-6alkyl group; linear or branched C1-6alcoxygroup; or halogen atom, in ring Y, Y1 represents CRY1, Y2 represents N or CRY2, Y3 represents N or CRY3, Y4 represents N or CRY4, RY1, RY2, RY3 and RY4 each independently represents hydrogen atom; linear or branched C1-6alkyl group, which can be substituted with halogen atom(s); C3-7alkyl group, which has ring structure; linear or branched C1-6alkoxygroup; halogen atom or cyanogroup, in ring Z, RZ represents linear or branched C1-6alkyl group, which can be substituted with halogen atom(s), or C3-7alkyl group, which has ring structure, which can be substituted with halogen atom(s). Invention also relates to particular compounds, DGAT1 inhibitor based on formula (I) compound, application of formula (I) compound, method of prevention or treatment of diseases, mediated by DGAT1 inhibition.

EFFECT: obtained are novel compounds, possessing useful biological activity.

19 cl, 19 tbl, 149 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new phenylpyrimidone derivatives of formula I possessing the properties of a phosphodiesterase type 5 (PDE5) inhibitor. The compounds of formula I can be used for treating various vascular disorders, such as erectile dysfunction, pulmonary arterial hypertension, etc. In formula each R1 and R2 independently means H; C1-C10alkyl; halogen; CF3; CN; OR5; NR6R7; NHCOR8; aryl; or C1-C4alkyl optionally substituted by OR5; Z means OR3; R3 means C1-C6alkyl or C1-C3alkyl, substituted by C1-C3alkoxy group; R4 means SO2NR6R7; NR9R10, providing NR9R10 is other than NH2; COR11; OR12; or R4 means 5-6-merous heterocyclyl optionally substituted by one or more substitutes specified in a group consisting of OH and C1-C6 alkyl; or R4 means 5- or 6-merous cyclic monosaccharide group; R5 means C1-C6alkyl; C1-C4alkyl optionally substituted by C1-C4alkoxy group; each R6 and R7 independently means H, OH, C1-C6alkyl, C1-C6alkoxy group, C3-C6alkenyl, C3-C6cycloalkyl, adamantyl, C3-C8lactamyl, aryl, Het or (CH2CH2O)jH, wherein j is 1-3; or each R6 and R7 independently means C1-C6alkyl, optionally substituted by OH, C1-C4alkoxy group, SO3H, SO2NR13R14, SO2R16, NR13R14, aryl, Het or 5-6-merous heterocyclyl; or each R6 and R7 independently means 5-6-merous heterocyclyl optionally substituted by one or more substitutes specified in a group consisting of C1-C6 alkyl and C1-C6alkyl substituted by hydroxyl; or R6 and R7 together with a nitrogen atom attached whereto form 5-7-merous heterocyclyl optionally substituted by one or more substitutes specified in a group consisting of OH, COOR8, (CH2CH2O)jH, wherein j is 1-3, C1-C4alkoxy group, Het and C1-C6alkyl substituted by aryl; or R6 and R7 together with a nitrogen atom attached whereto form a glucosyl amino group, an amino acid residue, a residue of an amino acid ester or an amino amide residue. The other radical values are specified in the patent claim.

EFFECT: invention refers to pharmaceutical compositions based on the above compounds, using them, methods for preparing the compounds, and intermediate products.

18 cl, 2 tbl, 224 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a method of producing a salt of tetrazole methanesulphonic acid of formula (I) , which involves acylating a compound (II) with a compound (III) and then adding methanesulphonic acid. The invention also relates to an intermediate compound of formula (II) and a method for production thereof.

EFFECT: method according to the present invention can cut reaction time, improve safety and enables to obtain salts of tetrazole methanesulphonic acid of high purity with high output without using a column chromatography technique.

22 cl, 2 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to 5-phenyl-1H-pyrazin-2-one derivatives of general formula II or pharmaceutically acceptable salts thereof, where R denotes -R1 or - R1-R2-R3; R1 denotes aryl or heteroaryl, and is optionally substituted with one or two R1'; where each R1' independently denotes C1-6alkyl, halogen or C1-6halogenalkyl; R2 denotes -C(=O), -CH2-; R3 denotes R4; where R4 denotes an amino group or heterocycloalkyl, and is optionally substituted with one or two substitutes selected from C1-6alkyl, hydroxy group, oxo group, C1-6hydroxyalkyl, C1-6alkoxy group; Q denotes CH2; Y1 denotes C1-6alkyl; Y2 denotes Y2b; where Y2b denotes C1-6alkyl, optionally substituted with one Y2b'; where Y2b' denotes a hydroxy group, n and m are equal to 0; Y4 denotes Y4c or Y4d; where Y4c denotes lower cycloalkyl, optionally substituted with halogen; and Y4d denotes an amino group, optionally substituted with one or more C1-6alkyl; where "aryl" denotes phenyl or naphthyl, "heteroaryl" denotes a monocyclic or bicyclic radical containing 5 to 9 atoms in the ring, which contains at least one aromatic ring containing 5 to 6 atoms in the ring, with one or two N or O heteroatoms, wherein the remaining atoms in the ring are carbon atoms, under the condition that the binding point of the heteroaryl radical is in the aromatic ring, "heterocycloalkyl" denotes a monovalent saturated cyclic radical consisting of one ring containing 5 to 6 atoms in the ring, with one or two ring heteroatoms selected from N, O or SO2. The invention also relates to use of the compound of formula II or a pharmaceutical composition based on the compound of formula II.

EFFECT: obtaining novel compounds that are useful for modulating Btk activity and treating diseases associated with excessive activity of Btk.

7 cl, 2 tbl, 53 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.

EFFECT: compounds of formula I and II as histone deacetylase inhibitors.

18 cl, 18 dwg, 10 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrole compounds of formula I or pharmaceutically acceptable salts thereof: I, where: Ar denotes phenyl, thiophenyl; R1 denotes imidazolyl, imidazolyl substituted with C1-C6alkyl, chlorine, bromine, fluorine, hydroxy group, methoxy group; R2 denotes H, CH3, Cl, F, OH, OCH3, OC2H5, propoxy group, carbamoyl, dimethylamino group, NH2, formamide group, CF3; X denotes CO and SO2. The compounds inhibit S-nitrosoglutathione reductase (GSNOR).

EFFECT: using the compound to produce a pharmaceutical composition and for treating asthma.

17 cl, 1 tbl, 14 dwg, 4 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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