Directly linked by a ring-member-to-ring- member bond (C07D403/04)

C   Chemistry; metallurgy(318327)
C07   Organic chemistry(61593)
C07D403/04                     Directly linked by a ring-member-to-ring- member bond(342)
Forzicyaside sulfate and its derivatives, method for its production and its application // 2642784
FIELD: pharmacology.SUBSTANCE: invention relates to forzicyaside sulfate and its derivative represented by the following formula , wherein R is Na+, K+ or NH+, and a method for their preparation, as well as an antiviral drug based on them and its use.EFFECT: increased efficiency of agents.10 cl, 9 tbl, 2 dwg
Comt inhibitors // 2642779
FIELD: pharmacology.SUBSTANCE: invention relates to new compounds of the formula (I) and their pharmaceutically acceptable salts which have the properties of a catechol-O-methyltransferase (COMT) inhibitor. In the compound of the formula (I) , where R1 is hydrogen, methyl, Br, F or Cl; R2 is hydrogen, lower alkyl, Br, I, C3-6cycloalkyl, C(O)O-lower alkyl, C(O)NH-lower alkyl substituted by halogen, C(O)(morpholine) or is 3,4-dihydronaphthalen-2-yl optionally substituted by lower alkyl, 1,2,3,4-tetrahydronaphthalen-2-yl, 2,3-dihydrobenzofuran-6-yl, 1-methyl-2,3-dihydro-1H-indolin-5-yl, 1-methylindolin-5-yl, tetrahydropyran-4-yl, 3,6-dihydro-2H-pyran-4-yl, 2-isopropyl-1,2,3-tetrahydroisoquinolin-5-yl, 2,3-dihydro- dimethyl[1,4]dioxin-6-yl, benzo[1,3]-dioxol-5-yl, 1,2,3,4-tetrahydroisoquinolin-7-yl optionally substituted by lower alkyl, cyclohexenyl, morpholinyl, 4-methylpiperazinyl, naphthalen-1-yl, naphtalen-2-yl, or represents (CHR)n-phenyl optionally substituted by one to five substituents R4, where R4 is F, Cl, CN, CH2-CN, lower alkyl, hydroxy, lower alkyl, substituted hydroxy, lower alkoxy, (CH2)1.2-lower alkoxy, S-lower alkyl, (CH2)1.2-S-lower alkyl, -CH2)1.2-S (O)2-lower alkyl, -S(O)2-lower alkyl, -S(O)2-di-lower alkylamino, -S(O)2-piperidinyl, lower alkyl substituted by halogen, -N=N-phenyl, di-lower alkylamino, (CH2)1.2-di-lower alkylamino, (CH2)2-NH-lower alkyl, NHC(O)-lower alkyl, lower alkoxy substituted by halogen, CH(CH3) C(O)O-lower alkyl, O-phenyl, O-benzyl, phenyl, optionally substituted CF3, SF5, benzyl, C(O)-lower alkyl, C(O)-phenyl, C(O)-morpholinyl, C(O)-4-methylpiperazinyl, C(O)-di-oxothiomorpholinyl, C(O)-piperidinyl, optionally substituted by F, C(O)-NH-(CH2)2-morpholinyl, C(O)-NR-(CH2)2-NR2, C(O)-N-di-lower alkyl, CH2-O-(CH2)2-4-methylpiperazinyl, CH2-O-(CH2)2-di-alkylamino, CH2-O-(CH2)2-pyrrolidinyl, CH2-O-(CH2)2-morpholinyl, CH2-O-(CH2)2-piperidinyl optionally substituted by lower alkyl substituted by halogen or lower alkyl, (CH2)3,4-pyrrolidinyl, (CH2)2,3-di-lower alkylamino, morpholinyl, CH2-morpholinyl, CH2-piperazine substituted by lower alkyl, -S(O)2-piperazine substituted by lower alkyl, CH2-O-C(O)-piperazine substituted by lower alkyl, pyrazolyl or (CH2)1,2-lower alkoxy; R is hydrogen, lower alkyl or hydroxyl; n is 0, 1, 2, or 3; or R2 is C(O)-phenyl optionally substituted by lower alkyl; or is -O-phenyl optionally substituted by F; or is CH=CH-phenyl optionally substituted by lower alkyl; or is C≡C-phenyl; or R2 is a heteroaryl selected from the group consisting of pyrazolyl, thiazolyl, pyridinyl, pyrimidinyl, imidazolyl, isoxazolyl, isothiazolyl, thiophenyl, 1-thia-3,4-diazolyl, imidazo[1,2-a]pyridinyl, indazolyl, quinolinyl or isoquinolinyl, and the said groups are optionally substituted by R5, where R5 is halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, lower alkoxy substituted by halogen, hydroxy, (CH2)1.2-lower alkoxy, CH2-di-lower alkylamino, di-lower alkylamino, morpholinyl, piperazinyl, pyrrolidin-1-yl, C(O)-piperidinyl, C(O)-4-methylpiperazinyl, phenyl optionally substituted by halogen, pyridinyl, S(O)2N(CH3)2, C(O)O-lower alkyl, NHC(O)-lower alkyl, or is C(O)-heteroaryl selected from pyridinyl and thiophenyl, where heteroaryl groups are optionally substituted by lower alkyl, n is 0, 1, 2 or 3; R3 is hydrogen, methyl, Br, F, Cl, CF3, nitro, amino, cyano, NHC(O)-phenyl, or is 1-methyl-1,2,3,6-tetrahydropyridinyl, or is pyridinyl optionally substituted by methyl or morpholinyl, or is phenyl optionally substituted by methyl , SO2CH3, CF3, CN, F or C(O)N (di-lower alkyl).EFFECT: compounds can be used to treat Parkinson's disease, depression, cognitive impairment and motor symptoms, resistant depression, cognitive impairment, mood and negative symptoms of schizophrenia.16 cl, 2 tbl, 256 ex
2-aminopyrasine derivatives as csf-1r kinase inhibitors // 2642777
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
ethod of producing nitronylnitroxyl radical 2-(5-methyl-1n-imidazole-4-yl)-4,5-bis(spiropentane)-4,5-dihydro-1n-imidazol-3-oxid-1-oxyl // 2642468
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing nitronylnitroxyl radical 2-(5-methyl-1N-imidazole-4-yl)-4.5-bis(spiropentane)-4.5-dihydro-1N-imidazole-3-oxide-1-oxyl, which consists in interacting 1.1'-dihydroxylation-bicyclopentyl produced by the neutralisation of the alkaline agent to the corresponding sulfate salt of 1,1'-dihydroxylation-bicyclopentyl, 4-methylimidazole-5-carbaldehydes in an aqueous solution when heated, and by the oxidation of the resulting product with sodium periodate, with the subsequent release of the specified nitronylnitroxide radical. .EFFECT: application as an effective and low-toxic contrast agent for MR-tomography of living organisms.2 ex
ethod for production of hydroxylated cyclopentapyrimidine compounds and their salts // 2642311
FIELD: biotechnology.SUBSTANCE: method for production of a formula III compound or a salt thereof, . The compound of formula or its salt is brought into contact with ketoreductase or alcohol dehydrogenase enzyme.EFFECT: invention allows stereoselective reduction of a compound of formula II or a salt thereof to a compound of formula III or a salt thereof that is suitable for further synthesis of ACT protein kinase activity inhibitors.15 cl, 3 dwg, 2 tbl, 6 ex
Anti-cancer benzopyrazines acting through fgfr-kinases inhibition // 2639863
FIELD: pharmacology.SUBSTANCE: invention relates to benzopyrazine derivatives of the general formula (I) , including any stereochemically isomeric form thereof, or a pharmaceutically acceptable salt thereof, wherein W is -N(R3)-; R2 is C1-4alkoxy; Y is -CR18=N-OR19 or -E-D; E is bond, C2-4alkynediyl, -CO-(CR22R23)s-, -NR22-(CR22R23)s-, -(CR22R23)s-CO-NR22-(CR22R23)s- or -(CR22R23)s-NR22-CO-(CR22R23)s-; D is phenyl, 3-6 membered cycloalkyl or 5-9 membered mono- or bicyclic saturated, partially saturated or aromatic heterocyclyl containing 1-4 heteroatoms selected from N, O or S, wherein the said phenyl, cycloalkyl and heterocyclyl can each optionally being substituted with 1-2 R1-groups; with the exception of the compounds indicated in the formula; R1 is halogen, cyano, C1-6alkyl, C1-6alkoxy, -C(=O)-O-C1-6alkyl, hydroxyC1-6alkyl, -NR4R5 , C1-6alkyl substituted by -O-C(=O)-C1-6alkyl, C1-6alkyl substituted by -NR4R5, -C(=O)-NR4R5, R6, C1-6alkyl substituted by R6, -C(=O)-R6; R3 is halogenC1-6alkyl, optionally substituted by -O-C(=O)-C1-6alkyl, hydroxyC1-6alkyl, hydroxyhalogenC1-6alkyl, C1-6alkoxyC1-6alkyl, where each C1-6alkyl may optionally be substituted by one hydroxyl group or -O-C(=O)-C1-6alkyl, C1-6alkyl substituted by R9, C2-6alkynyl substituted with R9, C1-6alkyl substituted by -NR10R11, C1-6alkyl substituted by -O-C(=O)-NR10R11; R4 and R5 are hydrogen, C1-6alkyl, C1-6alkyl substituted by -NR14R15, hydroxyC1-6alkyl, C1-6alkoxyC1-6alkyl, where each C1-6alkyl may optionally be substituted by one hydroxyl group, -C(=O)-NR14R15, -C(=O)-O-C1-6alkyl, -C(=O)-R13; R6 is a 6-membered saturated or aromatic monocyclic heterocyclyl having 1 to 2 heteroatoms selected from N or O; the said heterocyclyl is optionally substituted by 1 substituent selected from C1-6alkyl, halogen, C1-6alkyl-O-C(=O)-; R9 is C3cycloalkyl or 3-6 membered monocyclic saturated, partially saturated or aromatic heterocyclyl containing 1-2 heteroatoms selected from N or O, the said heterocyclyl is optionally substituted by 1 substituent selected from =O, hydroxyC1-4alkyl, C1-4alkyl-C(=O)-, C1-4alkyl substituted by -NR14R15, C1-4alkoxy; R10 and R11 are hydrogen, C1-6alkyl, halogen C1-6alkyl, hydroxyC1-6alkyl or C1-6alkyl substituted by carboxyl; R13 is a saturated 6-membered monocyclic heterocyclyl containing 1-2 heteroatoms selected from N and O; R14 and R15 are hydrogen or C1-4alkyl; R18 and R19 are C1-6alkyl; R22 and R23 are hydrogen; n=2; s=0, 1, 2, or 3. Invention also relates to a pharmaceutical composition and a product based thereon, the use of a compound of formula (I) and a method of prevention or treatment of conditions mediated by FGFR kinase.EFFECT: new derivatives of benzopyrazine, useful for cancer treatment.28 cl, 4 tbl, 54 ex
Dna-pk inhibitors // 2638540
FIELD: biotechnology.SUBSTANCE: invention relates to a novel compound of formula (I) or a pharmaceutically acceptable salt thereof, inhibiting DNA-dependent protein kinase (DNA-PK). The compounds can be used in the treatment of cancer. The compounds have a radiosensitizing effect on the line of cancer cells sensitive to radiation and can be used to enhance the effect of the therapeutic regimen for the treatment of cancer. In general formula (I), X is N or CRA5; RA1is F, C1-4-alkyl, C3-5cycloalkyl, OC1-4-alkyl, OC1-4-alkyl-C3-5cycloalkyl, NH2, NHC1-4-alkyl, NHC1-4-alkyl-C3-5cycloalkyl or C0-4-alkylheterocyclyl, the said heterocyclic ring system being selected from oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, or morpholinyl, and each of the said alkyl, cycloalkyl or heterocyclyl is optionally substituted with a maximum of three F atoms, a maximum of three 2H atoms, a maximum of two non-hemin OH groups, or a maximum of two OC1-2-alkyl; each RA4 is independently H or 2H; RA5 is hydrogen, F, C1-4-alkyl or OC1-4-alkyl, each of the said alkyls being optionally substituted with a maximum of three F atoms or a maximum of three 2H atoms; RB3 is C (O) NHC1-4-alkyl. The said alkyl is optionally substituted with a maximum of three F atoms, a maximum of three 2H atoms, a maximum of two non-hemin OH groups, or a maximum of two OC1-2-alkyl; and each RB4 is independently hydrogen, deuterium, F, or C1-4-alkyl.EFFECT: improved compound properties.18 cl, 3 tbl, 14 ex
Inhibitors of lrrk2 kinases activity // 2637936
FIELD: pharmacology.SUBSTANCE: R1, R2, R3 and R4 values are defined in the claims of this invention. Compounds of the formula (I) inhibit the LRRK2 activity. In addition, the invention relates to particular compounds as defined in claim 14. The invention also relates to a pharmaceutical composition comprising the compounds of the invention and to a method for neurodegenerative diseases treatment, for example those in which the disease is represented by α-synucleinopathy and in particular to a method for treatment of various diseases of the Parkinson's disease type, as well as a method for treatment of autoimmune diseases, such as Crohn's disease or ulcerative colitis.EFFECT: new method for neurodegenerative diseases treatment.22 cl, 10 tbl, 15 ex
Derivatives of isoindole [2,1-a]chinazoline for stabilizing organic materials // 2637807
FIELD: chemistry.SUBSTANCE: invention relates to a composition comprising a) an organic material susceptible to oxidative, thermal, or light degradation, which is a polymer, an oligohydroxy compound, wax, fat or mineral oil, provided that the polymer is not polypeptide, agar-agar, or an agar- agar component, and the oligohydroxy compound is not glucose or an agar-agar component; b) a compound of formula I, wherein n is 1, R5 is H, C1-C12-alkyl, C6-cycloalkyl, C6-aryl, OH, C1-alkoxy, C7-aralkyloxy, R1-R4 and R6-R9 each is independently of one another, H, C1-alkyl, C1-alkoxy, halogen; c) an additional additive, which is a phenolic antioxidant; and d) the second additional additive, which is phosphite. The invention also relates to the use of the said composition, a method of protecting an organic material, a compound of formula , and an additive composition based on a compound of formula (I).EFFECT: composition is produced useful for protecting an organic material susceptible to oxidative, thermal, or light degradation.15 cl, 7 tbl, 23 ex

Anti-viral compound production // 2636943
FIELD: pharmacology.SUBSTANCE: invention relates to a process for preparation of a compound of formula I or a pharmaceutically acceptable salt thereof comprising (A) reaction of a combination of formula compound (i) with formula compound (ii) in the presence of a metal catalyst and a base to obtain a compound of formula (iii) or a salt thereof; (B) deprotection of a compound of formula (iii) to obtain a compound of formula (iv) or a salt thereof; (C) bringing the compound of formula (iv) into contact with (S)-2-(methoxycarbonylamino)-3-methylbutanoic acid to obtain a compound of formula I; each PG being independently t-butoxycarbonyl, benzyloxycarbonyl or methoxy or isopropyloxycarbonyl protecting group; Y and Z are independently selected from Br and -B (OR)(OR'), where Y is -B (OR)(OR'), then Z is Br and Y is Br, then Z is - B(OR)(OR'); and R and R' are independently selected from the group consisting of hydrogen and straight or branched C1-8-alkyl, or R and R' together represent C3-8-cycloalkylene, wherein any alkyl or cycloalkylene is optionally substituted by one or more C1-6-alkyl groups. The invention also relates to intermediates and their crystalline forms.EFFECT: useful for hepatitis treatment.26 cl, 2 dwg, 2 ex
Substituted pyrrolidines as xia factor inhibitors for thromboembolic diseases treatment // 2636050
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the general formula , their pharmaceutically acceptable salts, pharmaceutical compositions containing the said compounds.EFFECT: compounds of general formula I are XIa factor inhibitors and are suitable for thromboembolic diseases prevention or treatment.22 cl, 1 tbl, 115 ex

New glp-1 receptor modulators // 2634896
FIELD: pharmacology.SUBSTANCE: compounds can be used in combination to reduce glucose with exenatide. In the formula IR or IS , A is a heteroaryl selected from imidazole, oxadiazole, thiadiazole, thiazole, oxazole, pyridine, pyrimidine, pyridazine, triazine; B is a heterocyclyl selected from isoxazole, oxazole, pyrimidine, pyrazole, thiazole, thiophenyl, thiadiazole, azepine, optionally fused to another nitrogen-containing 6-membered heterocyclic ring; C is an aryl selected from phenyl and naphthyl, benzyl; Y1 and Y2 are absent; Z is -C(O)-; each R1 is independently H or C1-4 alkyl; R2 is -O-R8, -N(R1)-SO2-R8, -NR41R42, -N(R1)-(CRaRb)m-COOH, -N(R1)-(CRaRb)m-CO-N(R1)-heterocyclyl, -N(R1)-(CRaRb)m-CO-N(R1)(R7) or -N(R1)-heterocyclyl, wherein R2 is not -OH or -NH2, and heterocyclyl is a 5-6 membered heterocyclyl containing 1 to 3 heteroatoms selected from N and S; each R3 and R4 is independently halogen, C1-C4alkyl, C1-C4alkyl substituted with R31, C1-C4alkoxy, halogenC1-C4alkyl, perhalogenC1-C4alkyl, halogenC1-C4alkoxy, -OH, -NR1R8, -C(O)R8, -C(O)NR1R8, -S(O)2R8, -OS(O)2R8, -(CRaRb)mNR1R8, -(CRaRb)mO(CRaRb)mR8; or any two R3 or R4 groups on the same carbon atom, taken together, form oxo, values of R31, R40, R41, R42 are indicated in the claims; W1 is absent; each Ra and Rb have values indicated in the claims; R5 is R7, -(CH2)m-L2-(CH2)m-R7 or -(-L3-(CRaRb)r-)s-L3-R7; R7, R8 have values indicated in the claims; L2 is independently, from the near to the far end of the structure of the formula I-R or I-S, absent or -O-; each L3 is independently absent, -O- or -N(R1)-, each m is independently 0, 1, 2, 3, 4, 5 or 6; each n is independently 0, or 1, or 2; P is 0, 1, 2, or 3; Q is 0, 1, 2, or 3.EFFECT: compounds have activity for glucagon-like peptide 1 and can be used to treat diseases for which modulation or potentiation of GLP-1R is prescribed, particularly for the treatment of diabetes.8 cl, 2 tbl, 381 ex
Pyridinone and pyridazinone derivatives // 2632915
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (I) or its pharmaceutically acceptable salts: , wherein J is a group of formula IIa, R1a is C1-C3alkyl; Y1a is N or CRxa, where Rxa is H, X2a is selected from the group consisting of: H, C1-C4alkyl; X1a is selected from the group consisting of: hydrogen, halogen, C1-C6alkyl, C1-C4haloalkyl,-O-C1-C4alkyl, -O-C1-C3alkylene-C3-C7cycloalkyl, -O-C1-C4haloalkyl, -O-C1-C3alkylene(5-membered heterocycloalkyl having 1 heteroatom selected from O), -O-C1-C6alkylene-N(R10)2, -O-C1-C3alkylene-C(O)OC1-C4alkyl, -C2-C4alkenylene-C(O)-O-C1-C4alkyl, -C(O)-C1-C4alkyl, C(O)O-C1-C4alkyl, C(O)NR10R12, -NR10-C1-C3alkylene-C(O)-C1-C4alkyl, -SO2NR10R12 and any of the groups: ii) 6-membered heterocycloalkenyl, which may be substituted with 1 R2; iii) 5-6 membered heterocycloalkyl with 1 to 2 heteroatoms selected from N, which may be substituted with 1-2 R3; iv) 5-6 membered heteroaryl with 1-3 heteroatoms independently selected from N, O, 9-10 membered bicyclic heteroaryl with 1 to 3 heteroatoms independently selected from N, S, which may be substituted with 1-2 R4; v) phenyl which may be substituted with 1-2 R6; X3 is LG where L is absent or is selected from the group consisting of: -O-, -O-C1-C3alkylene; and G is selected from the group consisting of: phenyl, 6-membered heteroaryl with 1 heteroatom selected from N, 9-membered bicyclic heteroaryl with 2 heteroatoms, selected from N, C3-C7cycloalkyl, 6-membered heterocycloalkyl with 1 heteroatom selected from N, O, where G may be substituted with 1-2 groups, A2 is CR18, and A1, A3 and A4 are CR19, values of the remaining substituents are indicated in the claims. The invention also relates to individual compounds, to a pharmaceutical composition and to a method for cancer treatment.EFFECT: new compounds with proliferative activity are obtained.20 cl, 6 tbl, 293 ex
Heterocyclic derivative and pharmaceutical means // 2632908
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic derivative or a pharmaceutically acceptable salt thereof, of the general formula , wherein ring A is a group represented by the general formulas , or , where X1 is NH, NC1-6alkyl or O; A1 is hydrogen; A2 is i) hydrogen; ii) halogen; iii) C1-6alkyl optionally substituted by one to three groups selected from a group consisting of halogen, amino, mono(C1-6alkyl)amino, di(C1-6alkyl)amino, carbamoyl, mono(C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, saturated cyclic aminocarbonyl, wherein the "saturated cyclic amino group" of the "saturated cyclic aminocarbonyl" part is 1-pyrrolidinyl, C1-6alkoxy and C1-6alkoxy-C1-6alkoxy; iv) C3-6cycloalkyl, optionally substituted by C1-6alkyl optionally substituted by one to three halogens; vi) a 4 to 5-membered saturated heterocyclic group containing one nitrogen or oxygen atom in the ring, optionally substituted by C1-6alkyl, (C1-6alkyloxy)carbonyl, (C1-6alkyl)carbonyl or hydroxy; (vii) C1-6alkylthio; (viii) C1-6alkylsulfonyl; ix) C1-6alkylsulfinyl; x) -NR3R4, where R3 and R4 are the same or different groups selected from a) hydrogen, b) optionally substituted C1-6alkyl, or c) C3-6cycloalkyl; or xi) saturated cyclic amino, wherein the "saturated cyclic amino" is piperidino, 1-piperazinyl or 4-morpholino, optionally substituted by C1-6alkyl, amino, mono(C1-6alkyl)amino, di(C1-6alkyl)amino, C1-6alkoxy or hydroxyl; R1 is phenyl, benzyl, naphthyl, C3-6cycloalkyl, C3-6cycloalkylmethyl, heteroaryl wherein heteroaryl is benzothiadiazolyl, benzothiazolyl, indolyl, 1,1-dioxobenzothiophenyl, quinolyl or 1,3-benzoxazol-2-yl, 1,2,3,4-tetrahydronaphthalen-5-yl, 1,2, 3,4-tetrahydronaphthalen-6-yl, 2,3-dihydro-1H-inden-4-yl, 2,3-dihydro-1H-inden-5-yl or C1-6alkyl, wherein the said phenyl, benzyl, cycloalkyl, cycloalkylmethyl and heteroaryl are optionally substituted; R2 is phenyl or pyridyl, wherein the said phenyl and pyridyl are optionally substituted. The invention also relates to a pharmaceutical composition and to an agent having the ability to inhibit mPGES-1 comprising a compound selected from the group consisting of a heterocyclic derivative of formula 1 and a pharmaceutically acceptable salt thereof as an active ingredient.EFFECT: heterocyclic derivatives possessing the inhibitory activity of mPGES-1.10 cl, 18 tbl, 257 ex
Substituted derivatives of 3-heteroaroylaminopropionic acid and their application as drugs // 2632897
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula I in any of its stereoisomeric forms or a physiologically acceptable salt thereof, wherein A is selected from the group consisting of C(R1) and N; D is selected from the group consisting of C(R2) and N; E is selected from the group consisting of C(R3) and N; L is selected from the group consisting of C(R4); where at least one and not more than two of A, D, E or L is N; G is selected from the group consisting of R71-O-C(O)-;R1 is selected from the group consisting of hydrogen, halogen; R2 is selected from the group consisting of hydrogen, halogen, (C1-C7)-alkyl, Het2 and Ar-CsH2s-, where s is 0; R3 is selected from the group consisting of hydrogen, Het2, R11-O-; R4 and R10 are selected from the group consisting of hydrogen, halogen; provided that one of the R2, R3 is a cyclic substituent; R11 is selected from the group consisting of hydrogen, R14; R12 and R13 are hydrogen; R14 is (C1-C10)-alkyl optionally substituted by one substituent, which is an oxo group; R30 is selected from the group consisting of R31, R32-CuH2u-, where u is 0; R31 is (C1-C10)-alkyl; R32 is phenyl, wherein phenyl is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-O-, CF3-; R40, R50, R60 and R71 are hydrogen; Ar, independently of other Ar groups, is selected from the group consisting of phenyl and aromatic 5-membered or 6-membered monocyclic heterocycle which includes one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and is bonded through the carbon atom of the ring, wherein phenyl and heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, HO-(C1-C6)-alkyl, Het4, (C1-C6)-alkyl-O-, -CF3, -CO-(C1-C6)-alkyl, -CO-NR12R13 and NC-; and wherein phenyl can be substituted with -CH=CH-CH=CH-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O- or -N((C1-C3)-alkyl) -CH=CH-; Het2 is a saturated 5-membered - 6-membered monocyclic heterocycle that includes a nitrogen atom in the ring through which Het2 is attached and optionally one other ring heteroatom selected from the group consisting of nitrogen and oxygen; Het4, regardless of other Het4 groups, is a saturated or unsaturated 4-membered to 5-membered monocyclic heterocycle that includes one to three ring heteroatoms selected from the group consisting of nitrogen and oxygen which is optionally substituted by one or more identical or different substituents selected from the group consisting of (C1-C4)-alkyl, HO-, (C1-C4)-alkyl-O-. Compounds of formula are obtained by the reaction of a compound of formula II with a compound of formula III, where the A, D, E, L, G, R10, R30, R40, R50 and R60 groups such as defined above for compounds of formula I, and additional functional groups may be present in protected form or in the form of a precursor group, and group J in the compound of formula II is HO-, (C1-C4)alkyl-O- or halogen.EFFECT: substituted derivatives of 3-heteroaroylaminopropionic acid for application as a pharmaceutical agent for catheptase protease A inhibition.10 cl, 1 tbl, 620 ex
Aza-aryl-1-h-pyrazol-1-yl-sulphonamides // 2627268
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) ,in which radicals and characters have values specified in the claims and their versions. The proposed compounds act as potent antagonists of CCR (9) receptor. Animal testing has shown that these compounds are useful for treatment of inflammation, disease with a hallmark for CCR (9). The compounds as a whole are arylsulfamide derivatives and are used in pharmaceutical compositions, methods for treatment of CCR (9) mediated diseases and as a control in assays for identification of CCR (9) antagonists.EFFECT: increased efficiency of compounds application.26 cl, 2 tbl, 33 ex
2-aryl-2,4-dihydroxy-2,5-dihydro-3-heteryl-5-oxo-1h-pyrrol-1-yl-4-methyl benzenesulphanolamides with analgesic activity // 2626650
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to the new methylbenzenesulfonamide derivatives of the formula (I) , where X=O, Ar=4-Me-C6H4 (a); X=O, Ar=4-Cl-C6H4 (b); X=NH, Ar=4-Cl-C6H4 (c).EFFECT: new compounds having analgesic activity were obtained.2 tbl, 4 ex
Azole derivatives // 2622639
FIELD: pharmacology.SUBSTANCE: invention relates to azole derivative of formula (I) or its pharmaceutically acceptable salt, wherein R1 is hydrogen atom or C1-5alkyl; R2 is hydrogen atom or C1-5alkyl; R3 is phenyl or pyridyl (where phenyl or pyridyl is optionally substituted with one or two fragments selected from the group consisting of C1-5alkoxy, halogen and trifluoromethyl atoms); each of R4 and R5, which can be the same or different, represent hydrogen atom or C1-5alkyl (where C1-5alkyl is optionally substituted with one fragment selected from the group consisting of hydroxy and C1-5alkoxy), or R4 and R5 together with nitrogen atom joining them form 4-7-membered saturated or unsaturated heterocycle, optionally compirsing one cyclic nitrogen, oxygen or sulfur atom, aside from the mentioned above joining nitrogen atom (where 4-7-membered saturated and unsaturated heterocycle is optionally substituted with one or two fragments, selected from the group consisting of hydroxy C1-5alkyl (where C1-5 alkyl is optionally substitued with one or two hydroxyl group), C1-5alkoxy, halogen atoms, cyano, C2-5alkanoyl, aminocarbonyl, mono-C1-5alkylaminocarbonyl, di-C1-5 alkylaminocarbonyl, trifluoromethyl, amino, mono-C1-5alkylamino, di-C1-5alkylamino and C2-5alkylamino, wherein the mentioned 4-7-membered saturated or unsaturated heterocycle optionally has C1-5alkylene fragment, joining two different cyclic carbon atoms), or form 2-oxa-6-azaspiro[3.3]hept-6-yl or 7-oxa-2-azaspiro[3.5]non-2-yl; azole cycle represented by formula (α) has any structure of group (II) formula, contained in invention formula, and wherein Ry is hydrogen atom or C1-5alkyl; X1 and X2 are such that: (i) if X1 means an ordinary link or fragment -CO-, X2 means -C1-5alkylene- or -O-C1-5alkylene-; and (ii) if X1 means a fragment -CONRx1-, X2means an ordinary link; Rx1 is hydrogen atom or C1-5alkyl; and cycle A is benzol cycle, pyridine cycle (where benzol cycle is optionally substituted with one or two fragments, selected from the group consisting of halogen atoms and C1-5alkoxy), 5-6-membered saturated or partly unsaturated heterocycle, containing one or two nitrogen atoms (where 5-6-membered saturated or unsaturated heterocycle is optionally substituted with one oxo group) or C3-7cycloalkane. The invention also relates to a pharmaceutical composition having antagonistic effect against V1b arginine-vasopressin receptor, and to agent for treating or preventing mood disorders, anxiety disorders or drug addiction, comprising azole derivative of formula (I) or its pharmaceutically acceptable salt as an active agent.EFFECT: azole derivative having antagonistic effect against V1b arginine-vasopressin receptor.12 cl, 22 tbl, 361 ex
Inhibitors of nonprilyzine // 2622288
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula , wherein R1 is selected from -OR7 and -NR8R9; R2 is H; X is -C1-9heteroaryl, selected from pyrazole, imidazole, triazole, benzotriazole, furan, tetrazole, pyrazine, thiophene, oxazole, isoxazole, thiazole, oxadiazole, pyridazine, pyridine, pyrimidine, benzoxazole, pyridylimidazole and pyridyltriazole; R3 is absent or is selected from H; Halogen; -C0-5alkylene-OH; -NH2; -C1-6alkyl; -CF3; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C (O) NR22R23; -NHC(O)R24; =O; -NO2; -C(CH3) =N(OH); Phenyl optionally substituted with one or two groups independently selected from halogen, -OH, -CF3, -OCH3, -NHC(O)CH3 and phenyl; Naphthalenyl; Pyridinyl; Pyrazinyl; Pyrazolyl optionally substituted with methyl; Thiophenyl, optionally substituted by methyl or halogen; Furanyl; and -CH2-morpholinyl; and R3, when present, is attached to a carbon atom; R4 is absent or is selected from H; -HE; -C1-6alkyl; -C1-2alkylene-COOR35; -OCH2 O(O)CH (R36)NH2; -OCH2O(O)CH3; -CH2CH(OH)CH2OH; and phenyl or benzyl optionally substituted with 1 to 3 groups selected from halogen, -COOR35, -OCH3, -OCF3 and -SCF3; and R4, when present, is attached to a carbon or nitrogen atom; or R3 and R4 are taken together to form -phenylene-O- (CH2) 1-3- or -phenylene-O-CH2-CHOH-CH2-; A is 0 or 1; R5 is halogen; B is 0 or an integer of 1 to 3; Each R6 is independently selected from halogen, -OH, -CH3 and -OCH3; R7 is selected from H, -C1-8alkyl, -[(CH2)2O]1-3CH3, -C1-6alkylene-OC(O)R10, -C0-6alkylenemorpholinyl, -C1-6alkylene-SO2-C1-6alkyl and the structure of formula (a); R10 is -O-C3-7cycloalkyl; and R32 is -C1-6alkyl; R8 and R9 are H; R20, R21 and R35 are independently selected from H and -C1-6alkyl; R22 and R23 are independently selected from H, -C1-6alkyl, -CH2COOH, -(CH2)2OH, -(CH2)2OCH3, - (CH2)2SO2NH2, -(CH2)2N(CH3)2, -C0-1alkylene-C3-7-cycloalkyl and -(CH2)2-imidazolyl; or R22 and R23 are taken together to form a ring; R24 is selected from -C1-6alkyl; -C0-1alkylene-O-C1-6alkyl; Phenyl optionally substituted by halogen or -OCH3; and pyridinyl; and R36 is -CH (CH3) 2; and wherein the methylene linker on the biphenyl is optionally substituted with one or two -C1-6 alkyl groups; or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are prepared by combining a compound of formula with a compound of formula 2 to provide a compound of formula I; Where P1 is also H. Also, the invention relates to an intermediate of formula 1, wherein P1 is H. The compounds of formula (I) are intended for the preparation of a medicament or pharmaceutical composition having inhibitory activity against non-prolamin (NEP). (a).EFFECT: compounds that have a non-lysine inhibitory enzyme activity.28 cl, 61 tbl, 25 ex

Substituted pyrimidinyl pyrroles active as kinase inhibitors // 2621732
FIELD: chemistry.SUBSTANCE: substituted pyrimidinyl pyrrole compounds or pharmaceutically acceptable salts thereof are selected from the group consisting of 5-(2-aminopyrimidin-4-yl)-2-[2-chloro-5-(trifluoromethyl) phenyl]-1H-pyrrole-3-carboxamide, 5-(2-aminopyrimidin-4-yl)-2-(2,5-dichlorophenyl)-1H-pyrrole-3-carboxamide, 5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-1H-pyrrole-3-carboxamide, 5-(2-minopyrimidin-4-yl)-2-[2-ethyl-5-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide, 5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-ethylphenyl)-N-methyl-1H-pyrrole-3-carboxamide, 5-(2-aminopyrimidin-4-yl)-2-(5 chloro-2-ethylphenyl)-N-ethyl-1H-pyrrole-3-carboxamide, 5-(2-aminopyrimidin-4-yl)-2-[2-chloro-5-(trifluoromethyl)phenyl]-N-methyl-1H-pyrrole-3-carboxamide, 2-(5-chloro-2-methylphenyl)-5-[2-(methylamino)pyrimidin-4-yl]-1H-pyrrole-3-carboxamide and 5-(2-aminopyrimidin-4-yl)-2-[2-ethyl-5-(trifluoromethyl)phenyl]-N-methyl-1H-pyrrole-3-carboxamide. The invention also relates to versions of the method for preparation of these compounds. For example, the method may include the steps (1): metal-catalyzed coupling reaction of a halogenated derivative of formula with a substituted phenylboronic acid of formula or henylboronic acid ester of formula , (2) alkaline hydrolysis of the obtained carboxylic acid ester of formula (3) amidation of the obtained carboxylic acid ester of formula by a reaction with a derivative of formula (VI) NHR8R9, to obtain a compound of formula wherein R1, R2, R3, R4, R8 and R9 values are given in the claims, and R12 is hydrogen; and if desired, convertion of a compound of formula (I) to a pharmaceutically acceptable salt or salt convertion to the free compound (I). Method versions include amidation of the carboxylic acid ester of formula (IV) without carboxylic acid (V) isolation or direct preparation of formula I compound without isolation of the intermediate compound of formula (IV) and (V). To prepare the formula I compound, where R12 is hydrogen, the method may include the steps of interaction of pyrrole of formula (VIII) with acetyl chloride to give compound IX, which forms enaminone X by reaction with dimethylformamide dialkyl acetal. Formulas VIII-XII are indicated in the claims.EFFECT: compound X is reacted with guanidine or its salt of formula XI and hydrolysis of the obtained pyrimidinyl pyrrole nitrile of formula XII is carried out under acidic conditions.10 cl, 1 tbl, 8 exалкил - alkyl

Derivatives of pyrrolopyrimidine useful as jak-kinases inhibitors // 2618673
FIELD: chemistry.SUBSTANCE: invention relates to a heterocyclic compound of the formula (I) or to its enantiomer, a diastereomer and a mixture thereof and a pharmaceutically acceptable salt thereof, wherein A: CH or N; L: bond or C1-2alkyl; R1 is selected from hydrogen, C1-4alkyl, heteroaryl, - (CH2)nC(O)OR15, -C(O)R15, -C(O)NR16R17, and -S(O)mR15, where each of alkyl or heteroaryl is possible is substituted with 1-3 groups selected from halogen, hydroxy, cyano, C1-2alkyl, C1-2alkoxy, C3cycloalkyl, C6aryl, pyridine and - (CH2)nC(O)OR15; R2 or R4 is independently selected from hydrogen and C1-2alkyl; R or R3 is independently selected from hydrogen and halogen; R5 or R6 is independently selected from hydrogen and C1-2alkyl; R7, R8, R9 or R10 is independently selected from hydrogen, C1-2alkyl and hydroxyC1-2alkyl; R11, R12, R13 or R14 is independently selected from hydrogen or R11 and R12 or R13 and R14 taken together form an oxo group; R15 is selected from C1-4alkyl, C3cycloalkyl, C2alkenyl, C6aryl and pyridine, wherein each of alkyl, cycloalkyl or heteroaryl is optionally substituted with 1 to 4 groups selected from halogen, hydroxy, cyano, C1-4alkoxy, C6aryl, tetrazole, -NR19R20, -S(O)mR18, -NHC(O)OR18 and -NHS(O)mR18; R16 or R17 is independently selected from hydrogen, C1-3alkyl and heteroaryl, wherein heteroaryl is optionally substituted by one selected from C1-2alkyl, hydroxy, C1-2alkoxy, C3cycloalkyl, hydroxyC1alkyl and-OR18; R18 is selected from C1-4alkyl and hydroxyC1-4alkyl; R19 or R20 is independently selected from the group consisting of hydrogen; M is 0, 1 or 2; N is 0 or 1; P is 0, 1 or 2; Q is 0 or 1; S is 1 or 2; And t is 1 or 2. The invention also relates to particular intermediates, a process for the preparation of a compound of formula (I), a pharmaceutical composition based on it, the use of a compound of formula (I), a method for inhibiting JAK kinases, and a method for treating certain diseases of the immune system.EFFECT: new heterocyclic compounds possessing the activity of JAK-kinase inhibitor have been obtained.22 cl, 7 tbl, 158 ex
Substituted methyl(2-{4-[3-(3-methanesulfonylamino-2-fluoro-5-chloro-phenyl)-1h-pyrazol-4-yl]pyrimidin-2-ylamino}ethyl) carbamates, process for their preparation and application // 2615986
FIELD: pharmacology.SUBSTANCE: invention relates to new substituted methyl (2-{4-[3-(3-methanesulfonylamino-2-fluoro-5-chloro-phenyl)-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-ethyl) carbamates of general formula 1 and pharmaceutically acceptable salts thereof, having the properties of BRAF-kinase inhibitor. The compounds may find application for prevention and/or treatment of cancer, such as malignant melanoma. In general formula 1 , R1 represents C1-C4alkyl, 3-oxetanyl; R2 and R3 together with the carbon atom to which they are attached form a C3-C6cycloalkyl, with one atom possibly replaced by an oxygen atom. The invention also relates to an intermediate compound of general formula 4 where R1, R2 and R3 are as defined above, Hal is a halogen selected from Cl, Br or I. The invention also relates to a process for formula 1 compound preparation. The method comprises reacting formula 2 reacting with amine 3 in the presence of a base, subsequent reaction of compound 4 with a suitable aryl boronic ester, in the presence of a palladium catalyst, tert-butyloxycarbonyl protecting group removal from compound 5 , and resulting amine 6 reacting with mesyl chloride in the presence of a base. The process is carried out according to Scheme 1 .EFFECT: increased efficiency of compounds application.13 cl, 5 ex, 2 dwg

Substituted picolinic acids and pyrimidine-4-carboxylic acids, method for production thereof, and use thereof as herbicides and plant growth regulators // 2612301
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula (I), N-oxide or salt thereof: ,where A denotes a residue, selected from a group consisting of A1, A2, A13 and A14: and , R1 denotes hydrogen or alkyl with 1–4 carbon atoms, R2 denotes chlorine, R3 denotes hydrogen, R4 denotes hydrogen, R5 denotes hydrogen, halogen, OH, NH2, CN, alkyl with 1–3 carbon atoms, alkoxy with 1–3 carbon atoms, alkylamino with 1–3 carbon atoms or cyclopropyl, R6 denotes hydrogen, halogen, OH, NH2, CN, alkyl with 1–3 carbon atoms, alkoxy with 1–3 carbon atoms, cyclopropyl or vinyl, R7 denotes hydrogen, halogen, alkyl with 1–3 carbon atoms, alkoxy with 1–3 carbon atoms, alkylthio with 1-3 carbon atoms, cyclopropyl, alkylamino with 1–3 carbon atoms or phenyl, R8 denotes hydrogen, alkyl with 1–3 carbon atoms, phenyl or alkylcarbonyl with 1–3 carbon atoms, X denotes N, CH, CCl, CF or CBr, n equals 0, 1 or 2, used as herbicides.EFFECT: substituted picolinic and pyrimidine-4-carboxylic acids, method for production thereof and use thereof as herbicides and plant growth regulators.7 cl, 45 tbl
Novel pyrazine derivatives // 2612138
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula (I), a pharmaceutically acceptable salt or ester thereof. Compounds of formula (I) modulate activity of cannabinoid receptor 2 (CB2). . In formula (I) R1 is a halophenyl or C3-C6-cycloalkyl-C1-C6-alkoxy; R2 is a C3-C6-cycloalkyl, azetidinyl or difluoroazetidinyl; one of R3 and R4 is hydrogen, and other is -(CR5R6)-R7 or -A-R7; or R2 is a C3-C6-cycloalkyl, and R3 and R4 together with a nitrogen atom, to which they are bonded, form piperidinylamine; R5 and6 are independently selected from hydrogen, C1-C6-alkyl, halogen-C1-C6-alkyl, C3-C6-cycloalkyl, C3-C6-cycloalkyl-C1-C6-alkyl, phenyl, phenyl-C1-C6-alkyl and halophenyl; or R5 and6 together with carbon atom, to which they are bonded, form C3-C6-cycloalkyl or oxetanyl; R7 is cyano, carboxy, 5-methyl-[1,2,4]oxadiazol-3-yl, 5-amino-[1,2,4]oxadiazol-3-yl, thiazolyl, C1-C6-alkylthiazolyl, pyridinyl, C1-C6-alkylaminocarbonyl, hydroxy-C1-C6-alkyl, C1-C6-alkoxy-C1-C6-alkyl, aminocarbonyl, C1-C6-alkoxycarbonyl, di-C1-C6-alkylaminocarbonyl, phenyl-C1-C6-alkyl, pyridinyl-C1-C6-alkyl, halogen-C1-C6-alkylaminocarbonyl, 5-phenyl-2-methyl-oxazol-4-yl-alkyl, aminocarbonyl-C1-C6-alkyl or halogen; and A is cyclohexyl or thiophenyl, under condition specified in patent claim. Invention also relates to individual compounds, pharmaceutical composition, use of compounds and to a method of modulating CB2 receptor activity.EFFECT: technical result is obtaining novel compounds of formula (I) modulating activity of cannabinoid receptor 2 (CB2).19 cl, 111 ex
Derivatives of 7-fluoro-8-chloro-5h-dibenzo [b, e] [1, 4] diazepine and their application // 2610169
FIELD: pharmacy.SUBSTANCE: compounds of 11-(4-methylpiperazin-1-yl)-7-fluoro-8-chloro-5H-dibenzo [b, e] [1,4] diazepine, 11-(piperazin-1-yl)-7-fluoro-8-chloro-5H-dibenzo [b, e] [1,4] diazepine, pharmaceutically acceptable salts, solvates or hydrates thereof are proposed to use for the manufacture of medicaments for treatment of therapy-resistant forms of schizophrenia. Pharmaceutical composition is also proposed.EFFECT: group of inventions allows creation of an effective drug, application of which for treatment of therapy-resistant forms of schizophrenia can eliminate both positive and negative symptoms of schizophrenia and cognitive disorders, and application of which does not cause serious side effects, that limit its use, including sedation, tachycardia, orthostatism, agranulocytosis and hygrostomia.10 cl, 5 dwg, 1 tbl, 7 ex

Compounds for treating cancer // 2609018
FIELD: chemistry.SUBSTANCE: invention relates to a compound of structural formula (XI), where X is NH; Q is NH or S; and A is a substituted or unsubstituted furanyl, indolyl, phenyl, biphenyl, triphenyl, diphenylmethane, thiophenyl, adamantanyl or fluorenyl; wherein said ring A is optionally substituted with 1-5 substituents, which are independently O-alkyl, O-haloalkyl, F, Cl, Br, I, haloalkyl, CF3, CN, -CH2CN, NH2, hydroxyl, -(CH2)iNHCH3, -(CH2)iNH2, -(CH2)iN(CH3)2, -OC(O)CF3, C1-C5 straight or branched alkyl, haloalkyl, alkylamino, aminoalkyl, -OCH2Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, -C(O)NH2 or NO2; and i is an integer from 0 to 5. Compound of formula (XI) can be in form of an isomer, pharmaceutically acceptable salt thereof, tautomer or hydrate. Invention also relates to a pharmaceutical composition for treating cancerous diseases, containing said compound and pharmaceutically acceptable carrier. Compound of formula (XI) is intended for treatment, suppression, reducing degree, reducing risk, inhibiting cancer, treating drug-resistant tumour or tumours or destruction of cancer cells. Said cancer is selected from a group consisting of prostate cancer, breast cancer, ovarian cancer, skin cancer, melanoma, metastatic melanoma, lung cancer, colon cancer, leukaemia, kidney cancer, CNS cancer and combinations thereof. Said tumour is selected from a group Consisting melanoma tumour, tumour metastatic melanoma, tumor of prostate cancer and ovarian tumour.EFFECT: technical result is compounds with anticancer activity.12 cl, 38 dwg, 33 tbl, 30 ex
Substituted n-{3-[4-(1-methyl-1h-indol-3-yl)pyrimidin-2-ylamino]-4-methoxyphenyl}-amides as modulators of egfr, applicable for treating cancer // 2606949
FIELD: chemistry.SUBSTANCE: invention relates to novel substituted N-{3-[4-(1-methyl-1H-indol-3-yl)pyrimidin-2-ylamino]-4-methoxyphenyl}-amides of general formula 1 and pharmaceutically acceptable salts thereof, having properties of modulators of EGFR and suitable for treating cancer, for example small cell lung cancer. In general formula 1 R1 represents CH2=C(R3)-, R3CH=CH-; R2 is (2-dimethylaminoethyl)-methylamino, 3-dimethylaminopiperidin-1-yl; R3 is fluorine, trifluoromethyl, dimethylcarbamoyl; or R2 is 3-dimethylaminopiperidin-1-yl; R3 is H; or mesylate compound 1, where R1 is C(CH3)≡C-, R2 is (2-dimethylaminoethyl)-methylamino. Preferable compounds are N-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-2-fluoro-acrylamide (1.2); N-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-4,4,4-trifluorobut-2-enamide (1.6); (E)-3-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenylcarbamoyl}-N,N-dimethylacrylamide (1.8); N-{2-(3-dimethylaminopiperidin-1-yl)-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-acrylamide (1.11); mesylate N-{2-[(2-dimethylaminoethyl)-methylamino]-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-2-butynamide (1.14⋅CH3SO3H) or mesylate N-{2-(3-dimethylaminopiperidin-1-yl)-5-[4-(1-methyl-1H-indol-3-yl)-pyrimidin-2-ylamino]-4-methoxyphenyl}-acrylamide (1.11⋅CH3SO3H). Invention also relates to a method of producing compounds of formula 1.EFFECT: method involves reacting a compound of formula 2 or its salt with activated derivative of corresponding organic acid, such as an acid, ester or organic acid anhydride.15 cl, 2 tbl, 14 ex

Amino-substituted 3-heteroaroylamino-propionic acid derivatives and use thereof as pharmaceutical agents // 2605600
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I in form of any of its stereoisomeric forms, or its physiologically acceptable salt, where A denotes C(R1); D denotes N(R2); E denotes N; G denotes R71-O-C(O)-; R1 is selected from a group consisting of hydrogen and NC-; R2 denotes Ar-CsH2s-, where s denotes an integer 0 or R2 and R11 together denote -C(R18)=C(R19)-; R10 is selected from a group consisting of R11, R12-N(R13)-C(O)- and R14-C(O)- and (C1-C4)-alkyl-S(O)m-; R11 is selected from a group, consisting of hydrogen and R14 or R10 and11 form Het2; R12 and R13 are independently selected from a group, consisting of hydrogen and Ar; R30 is selected from a group, consisting of R31, (C3-C7)-cycloalkyl, R32-CuH2u-, where u denotes an integer selected from a group consisting of 0, 2 and 3; R40 is selected from a group consisting of hydrogen and (C1-C-4)-alkyl; R50 denotes hydrogen; R60 denotes hydrogen or R30 and R50 together denote (CH2)z, optionally substituted with one or more identical or different (C1-C4)-alkyl substitutes, where z denotes an integer selected from a group consisting of 3, 4 and 5; R71 denotes hydrogen; Ar, independently from each other group Ar, is selected from a group consisting of phenyl and aromatic 5-member or 6-member monocyclic heterocycle, which comprises one cyclic heteroatom selected from a group, consisting of nitrogen, oxygen, and is bonded to other part of molecules through a cyclic carbon atom, where phenyl is optionally substituted with one or more identical or different substitutes, selected from a group consisting of halogen, (C1-C6)-alkyl; Het2 denotes a saturated 5-6-member monocyclic heterocycle, which includes cyclic nitrogen atom, through which Het2 is bonded to other part of molecule, and optionally one additional cyclic heteroatom, selected from sulphur, optionally substituted with one or more substitutes, selected from oxo; m independently from each other m denotes 2. Invention also relates to a method of producing a compound of formula I or a physiologically acceptable salt thereof, which includes reacting a compound of formula II with a compound of formula III, where groups A, D, E, G, R10, R11, R30, R40, R50 and R60, in compounds of formulae II and III, are defined as groups in compounds of formula I, and, furthermore, there may be functional groups, which can be in protected form or in form of precursor groups, and group J, which is part of compound of formula II, denotes HO-, (C1-C-4)-alkyl-O- or halogen. Compound of formula I or physiologically acceptable salt thereof are intended for use as a pharmaceutical agent for inhibiting of protease of cathepsin A.EFFECT: technical result is amino-substituted 3-heteroaroylamino-propionic acid derivatives as cathepsin A inhibitor.8 cl, 1 tbl

Neprilysin inhibitors // 2605557
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I, where R1 is -OR7; R2 is H; X is selected from a pyrazole, triazole, benzotriazole, tetrazole, oxazole, isoxazole, thiazole, pyridazine, pyrimidine and pyridyl triazole; R3 is absent or is selected from H; halogen; -C0-5alkylene-OH; -C1-6alkyl; -C3-7cycloalkyl; -C0-2alkylene-O-C1-6alkyl; -C(O)R20; -C0-1alkylene-COOR21; -C(O)NR22R23; -NHC(O)R24; =O; phenyl, optionally substituted with one or two groups independently selected from halogen, -OCH3, -NHC(O)CH3 and phenyl; naphthalenyl; pyridinyl; pyrazinyl; and R3, when present, is bonded to carbon atom; R4 is selected from H; -OH; -C1-2alkylene-COOR35; -pyridinyl; and phenyl or benzyl, optionally substituted by one or more groups selected from halogen and -OCH3; and R4, when present, is bonded to carbon atom or a nitrogen atom; a equals 0 or a equals 1; and R5 is selected from halogen and -CN; b is equal to 0 or 1, and R6 is selected from Cl, F, -OH, -CH3, -OCH3 and -CF3; or b is equal to 2, and R6 each is independently selected from halogen, -OH, -CH3, or -OCH3, or b is equal to 3, and R6 each is independently selected from halogen or -CH3; R7 is selected from H, -C1-8alkyl, -C1-3alkylene-C6-10aryl, -C0-6alkylene morpholinyl or dioxol-2-one methyl, of formula (a); or a pharmaceutically acceptable salt thereof. Compounds of formula (I) are obtained by condensation of compound of formula 1 with a compound of formula 2, where P1 is H or tert-butoxycarbonyl; and wherein method further includes removal of protective group of compound of formula 1, when P1 is tert-butoxycarbonyl. Also compound of formula (I) is obtained by removing protective group of compound of formula (6) or salt thereof; where R1P is -O-P3, where P3 is methyl. Invention also relates to intermediate compounds of formulae (1) and (6). Compounds of formula (I) are intended for inhibiting neprilysin activity.EFFECT: compounds having neprilysin inhibiting activity.19 cl, 9 ex,(а), ,

Dichloroacetate of n1,n2-disubstituted n4-[4-(1-methyl-1h-indole-3-yl)-pyrimidine-2-yl]-5-methoxybenzene-1,2,4-triamine as egfr modulator for treating cancer // 2603960
FIELD: chemistry, medicine.SUBSTANCE: invention relates to novel salt - dichloroacetate N-{2-[(2-dimethylaminoethyl)methyl-amino]-5-[4-(1-methyl-1H-indole-3-yl)pyrimidin-2-ylamino]-4-methoxyphenyl}acrylamide, which has properties of EGFR inhibitor and can be used for treating cancer types, mediated by EGFR and its mutants selected from L858R, 1790M and Exon19. Compound may be used for treating ovarian cancer, cervical cancer, colorectal cancer, breast cancer, pancreatic cancer, glioma, glioblastoma, prostate cancer, melanoma, leukemia, non-Hodgkin lymphoma, stomach cancer, lung cancer and hepatocellular cancer, gastrointestinal stromal tumors (GIST), thyroid cancer, bile duct cancer, endometrial cancer, renal cancer, anaplastic large cell lymphoma, acute myeloid leukemia, multiple myeloma, melanoma and mesothelioma. Preferably compound can be used for preventing and/or treating mutations of epidermal growth factor receptor EGFRm of non-small cell lung cancer (NSCLC), which also have resistent mutation T790M. N-{2-[(2-dimethylaminoethyl)methyl-amino]-5-[4-(1-methyl-1H-indole-3-yl)pyrimidin-2-ylamino]-4-methoxyphenyl}acrylamide dichloroacetate corresponds to general formula 1.EFFECT: prevention and/or treatment of mutations of epidermal growth factor receptor EGFRm in non-small cell lung cancer (NSCLC).12 cl, 2 tbl, 6 ex

Substituted quinazine derivatives as fgfr-kinase inhibitors for treatment of cancer // 2602233
FIELD: pharmaceutics.SUBSTANCE: invention is related to compounds of formula I, pharmaceutical compositions based thereon, use thereof for treating cancer, FGFR-kinase mediated, and methods of their production. In general formula I n is any integer, equal to 0, 1 or 2; R1 is C1-6alkyl; each group R1a represents hydrogen; each group R2 is C1-4alkoxy; R3a is-NR10R11, hydroxyl, gidroksiC1-6alkyl, cianoC1-6alkyl, C1-6alkyl substituted R9, C1-6alkyl substituted -NR10R11, C1-6alkyl substituted hydroxyl and -NR10R11, C1-6alkyl substituted -C(=O)-NR10R11; R3b is hydrogen or hydroxyl; provided that if R3a is -NR10R11, then R3b is hydrogen; or R3a and R3b are taken together to form =O, to make cyclopropyl together with carbon atom, with which they are bonded or to make =CH-C0-4alkyl, substituted R3c; R3s is-NR10R11 or cyano; R9 is a 5-7-member monocyclic heterocyclic ring, containing at least one heteroatom, selected from N, O or S, where 5-7-member monocyclic heterocyclyl is optionally substituted = O; R10 and R11 group each independently represents hydrogen, C1-6alkyl, C1-6alkyl substituted-NR14R15, or halogenC1-6alkyl; R14 and R15 group each independently denotes hydrogen or C1-4alkyl.EFFECT: treatment of cancer.34 cl, 4 tbl, 10 ex

Primary amine diazeniumdiolate heterocyclic derivatives // 2596867
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula I or pharmaceutically acceptable salts thereof, which have antihypertensive action. In formula I X represents O or NR7; group is bonded to any carbon ring atom, different from carbon atom to which are bonded R1 and R2; R1 represents hydrogen or together with R2 forms =O; R2 represents hydrogen or together with R1 forms =O; R4 is -C1-6alkyl; R5 and R6, which are bonded to any available carbon ring atom, independently represent hydrogen or R5 and R6 in cases when they are bonded to same carbon atom, form =O; R7 is -C1-6alkyl, -C(O)O-C-1-6alkyl, -C(O)O-C-1-6alkylene-CR8R9R10, -C(O)C1-6alkyl, -C(O)OC3-6carbocycle, -C(O)aryl, -C(O)heteroaryl, where heteroaryl is unsaturated 5- or 6-member ring containing 1-4 heteroatoms selected from N, -C(O)NHC1-6alkyl, -C(O)NH-adamantyl, -SO2C1-6alkyl, aryl or unsaturated 5- or 6-Member heteroaryl ring containing 1-4 heteroatoms selected from N, where aryl, alkyl, alkylene, carbocycle and heteroaryl are unsubstituted or substituted with 1-4 groups independently selected from -CN, halogen, -CF3, -OCF3, -C(O)NH2, -C-1-6alkyl, aryl, unsaturated 5-member heteroaryl ring with 1-3 nitrogen atoms, where R8 and R9 together with carbon atom to which they are bonded form C3-6carbocycle or 4-8-member heterocycle containing an oxygen atom, and where R10 is C1-6alkyl.EFFECT: invention also relates to pharmaceutical compositions containing said compounds, and a method of treating hypertension.29 cl, 43 ex

Use of ammonium salts of trifluorborane as an antibacterial and anti-mitotic agent // 2595037
FIELD: chemistry.SUBSTANCE: present invention relates to the use of ammonium salts of trifluoroborane of formula I for preparing a drug possessing antibacterial (bactericidal) and antimycotic (antifungal, fungicidal) activity against Salmonella r. B, Candida Albicans, Pseudomonas aeruginosa. Ammonium salts of trifluoroborane correspond the general formula I , where R denotes h-C-8H17; n-(C)10H21, n-C12H25; n-C14H29; n-C16H33, n-C-18H37.EFFECT: compounds are characterised by a broad temperature stability interval up to 250-300 °C in the form of liquid crystals and can be used in medicine, veterinary science, agriculture.1 cl, 1 tbl, 7 ex

Substituted 1-(1-tert-butyl-1h-imidazol-4-yl)-1h-1,2,3-triazoles, method for production thereof and fungicide composition based thereon // 2591206
FIELD: chemistry.SUBSTANCE: invention relates to substituted 1-(1-tert-butyl-1H-imidazole-4-yl)-1H-1,2,3-triazoles of general formula I, having fungicidal activity. In general formula I R denotes a hydrogen atom, trimethylsilyl group, cycloalkyl (CnH2n-1, with n from 3 to 7), substituted phenyl, having as substitutes fluorine, chlorine, trifluoromethyl or methyoxy group. Invention also relates to method for producing of substituted 1-(1-tert-butyl-1H-imidazole-4-yl)-1H-1,2,3-triazole and to fungicidal composition.EFFECT: technical result is obtaining novel compounds having fungicidal activity.3 cl, 7 tbl, 9 ex

ethod of producing imides of maleopimaric acid methyl ether // 2591193
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a method of producing imides of maleopimaric acid. Method involves condensation of methyl ether of maleopimaric acid with amines in an organic solvent at high temperature with subsequent cooling of reaction mass to room temperature and addition of water for extraction of end product. Method is characterised by that molar ratio of methyl ether of maleopimaric acid: amine is equal to 1:2, organic solvent used is dimethyl sulphoxide, and process takes place at temperature 120-160 °C under conditions of ultrasonic action during 30-40 minutes.EFFECT: method increases output of end products and reduces duration of synthesis.3 cl, 1 tbl, 2 ex

Novel 4-amino-n-hydroxybenzamides as hdac inhibitors for treating cancer // 2591190
FIELD: pharmaceutics.SUBSTANCE: invention relates to the HDAC inhibitors of formula (I) or pharmaceutically acceptable salts, esters or stereoisomers, where R1 represents hydrogen or halogen; R2 represents hydrogen, C1-4-alkyl; R3 is phenyl, unsubstituted or substituted with one or two or three times a halogen, C1-4-alkyl, C1-4-alkoxy, C1-4-alkylsulfonyl, cyano, trifluoromethyl, phenyl, phenoxy, pirrolyl, imidazonyl, oxazolyl or di C1-4-alkylamino-C1-4-alkoxy; naphthalenyl; quinolinyl; C3-7-cycloalkyl; phenylalkyl, where phenyl may not be substituted by or once or twice substituted by halogen, C1-4-alkoxy, phenyl; naftalinilalkyl; phenylcycloalkyl; pyrimidinyl; phenylsulfonyl, where phenyl may not be substituted by or once or twice substituted by halogen, phenyl; or phenylcarbonyl, where phenyl may not be substituted by or once or twice substituted by halogen, C1-4-alkoxy; R4 is hydrogen or C1-4-alkyl; Y represents -CH2- or -C=O; or R4 and Y together with carbon atom to which R4 is connected, can form a phenyl ring or a pyridine ring, which may not be substituted with or substituted with halogen; provided that R2 is C1-4alkyl; A represents -C=O, -CH2- or -CH-alkyl, provided that a and Y simultaneously does not represent -C=O.EFFECT: presented are pharmaceutical compositions of these compounds and use thereof as drug for treating cancer.14 cl, 3 tbl, 101 ex

Novel triazole compounds // 2588137
FIELD: pharmaceuticals.SUBSTANCE: invention relates to compounds of formula (I), pharmaceutically acceptable salts and esters. Compounds of formula (I) have affinity and selectivity for GABA A α5 receptor. In formula X is N or CH; R1, R2 - C1-C7-alkyl, phenyl substituted by 1 halogen, wherein one of substituents R1 and R2 is an alkyl group; R3 - haloC1-C7-alkyl, nitro, -C(O) R4, -C(O) NR5R6; R4 - C1-C7-alkyl, hydroxy, C1-C7-alkoxy; R5 - hydrogen, C1-C7-alkyl, haloC1-C7 alkyl hydroxyC1-C7-alkyl, -(CH2)n-C3-C8 cycloalkyl, - (CH2)n- (4-6 membered heterocycloalkyl with 1 heteroatom selected from O), wherein heterocycloalkyl is optionally substituted with one C1-C7-alkyl group; n is an integer ranging from 0 to 1; R6 - hydrogen, C1-C7-alkyl; or R5 and R6 together with nitrogen to which they are attached form a bicyclic 7-membered heterocycloalkyl with additional heteroatom selected from O, 6-membered heterocycloalkyl with additional heteroatom selected from O, S, wherein heterocycloalkyl is optionally substituted by one or more oxo groups. Invention also relates to a pharmaceutical composition comprising a compound of invention in an effective amount, to a method for treating or preventing diseases associated with GABA A α5 receptor, use of compounds for preparation of medicaments and use of compounds for treating or preventing diseases associated with GABA A α5 receptor.EFFECT: technical result is obtaining novel compounds having affinity and selectivity for GABA A α5 receptor.23 cl, 1 tbl, 53 ex

Diaminopyrimidine derivatives and methods for production thereof // 2587981
FIELD: pharmaceutics.SUBSTANCE: present invention relates to a novel compound of diaminopirimidine formula 1 or its pharmaceutically acceptable salts possessing the properties of 5-HT4 receptors agonist. 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, C1-2alkyl (where C1-2alkyl optionally substituted with halogen), C1-5alkoxy,C1-5alkylthio, C1-5alkoxycarbonyl and aminokarbonil, or heteroaryl group selected from a group consisting of furanyl, pyrrolyl, tiofenil, hinolinil, hromenonil, indolil, benzimidazole-4-yl, benzimidazole-5-yl, benzimidazole-6-yl, benzimidazole-7-yl and indazolil, herewith the heteroaryl group can be optionally substituted with one or more substitutes selected from a group consisting of C1-5alkyl (where C1-5alkyl optionally substituted with halogen) and C1-5alkoxy, R2 denotes a nitrogen-containing cyclic group selected from a group consisting of the following formulae from A to D (where * symbol in A-D formulae denotes the position of this group attachment to a compound of formula (1))R3 denotes C1-5alkyl group, optionally substituted by phenyl, R4 denotes hydrogen, C1-5alkyl group optionally substituted with a substitute selected from a group consisting of hydroxy, C1-5alkylamino, pyrrolidinyl and hydroxy-C-1-5alkylamino; C1-5alkoxycarbonyl group or amin-carbonyl group, R5 denotes hydrogen, hydroxyl group; C1-5alkoxy group; C1-5alkyl group, optionally substituted with a substitute selected from a group consisting of amino and C1-5alkoksikarbonilamino; or group selected from a group consisting of the following formulae of E to I (where * symbol in E-I formulae is the position of this group attachment to one of the of A-D formula compounds),R6 means hydrogen, hydroxyl group or C1-5alkyl group optionally substituted with hydroxy, X denotes -CH(R7)-, -C(=O)-, -N(R8)- or -O-, R7 means hydrogen; hydroxyl group; amino-carbonyl group; phenyl group or C1-5alkyl group optionally substituted with hydroxy, R4 and R5, R5 and R6, R4 and R6 or R5 and R7 may be interconnected while forming 5- or 6-element ring; the said ring may be carbocyclic or additionally contain an oxygen atom as a heteroatom, R8 denotes hydrogen or C1-5alkyl group. Values of R9-R12 radicals are given in the patent claim.EFFECT: invention relates to the use of formula 1 or its pharmaceutically acceptable salt for preparing a drug in order to prevent or treat gastrointestinal motility dysfunction; Gastrointestinal motor dysfunction is gastroesophageal reflux disease (GERD), a lock (constipation), an irritable bowel syndrome (IBS), dyspepsia, postoperative intestinal obstruction, prolonged gastric emptying, gastroparesis, intestinal pseudo-obstruction, content transit deceleration over the colon induced by medicines or diabetic gastroparesis.8 cl, 38 tbl, 355 ex

Diaminopyrimidine derivatives and methods for production thereof // 2587493
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

Synthesis and anticancer activity of derivatives of aryl and heteroaryl quinolines // 2584688
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I and pharmaceutically acceptable salts thereof , where R is hydrogen, RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2; W represents 2-halogenphenyl, 3-halogenphenyl or 4-halogenphenyl; R5 is (C1-C6)alkoxy, hydroxyl or OR8; R6 is hydroxyl or (C1-C6)alkoxy; R7 represents hydrogen, hydroxyl or O-(C1-C6)alcylenphenyl; R8 represents a RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2, and m is monovalent metal ion; or where R is hydrogen, RO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2; W represents 2-halogenphenyl, 3-halogenphenyl or 4-halogenphenyl; R5 represents hydrogen, (C1-C6)alkoxy, hydroxyl or OR8; R6 is (C1-C6)alkoxy; R7 is hydroxyl or O-(C1-C6)alcylenphenyl; R8 represents PO(OH)2, P(=O)(O-(C1-C6)alcylenphenyl)2 or P(=O)(OM)2, and m is monovalent metal ion. Disclosed compounds have anti-cancer activity. Invention also relates to compounds of formula I, radicals of which are presented in patent claim and to using pharmaceutical composition containing effective amount of compound of invention for treating cancer.EFFECT: technical outcome is new compounds possessing anticancer activity.17 cl, 23 dwg, 7 tbl, 4 ex
Novel compositions and methods of controlling nematodes as pests // 2582997
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula I or its pesticide acceptable salts. Compound of formula I may be effective against plants parasitic eelworms. In formula I is optionally substituted phenyl or pyridyl, said substitutes are selected from group consisting of CH3, CF3, F, Cl, Br, OCH3 and CN; C is heteroaryl, selected from group consisting of 3-thienyl and 3-furanyl, each independently can be optionally substituted with one or more substitutes selected from group consisting of: F, Cl, Br and CH3, or C is selected from group consisting of 1-pyrrolidinyl, 1-pyrrolyl and 2-pyrrolyl, each of which can be optionally independently substituted with one or more substitute selected from group consisting of methyl and halogen. Invention also relates to compounds of formula II or its pesticide acceptable salts, and to methods of controlling plants parasitic eelworms. EFFECT: technical result is obtaining new compounds having anti-eelworms activity.21 cl, 5 tbl, 7 ex
Sgc stimulators // 2582679
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula IA or IB or their pharmaceutically acceptable salts. The compounds of formula IA or IB possess sGC-stimulating activity. In formulas IA and IB , a circled B symbol means B ring, and B ring represents phenyl; n is equal to an integer specified in 0 to 1; each JB is independently specified in halogen; X is specified in N or C-H; D ring represents a 6-merous ring having X in formula IA, or a 5-merous ring having Y in formula IB; each Y is independently specified in C-H, C, N, O or S and independently substituted by JD when Y represents C or N; each of bonds between the two neighbouring atoms Y or between neighbouring Y and N in formula IB independently represents a single or double bond depending on whether Y is C, N, O or S, and D ring is aromatic; m is equal to an integer specified in 0 to 3; each JD is a substituted on a halogen or nitrogen atom of the ring and independently specified in halogen, -C(O)N(RD)2, -N(RD)2, -N(Rd)C(O)RD, -N(Rd)C(O)ORD, a 4-8-merous heterocyclic ring, wherein each specified 4-8-merous heterocyclic ring contains 1 to 2 heteroatoms independently specified in O, N or S; RC is specified in halogen, -CN, C1-6alkyl or C ring. The invention also refers to individual compounds and a pharmaceutical composition containing the compound of the invention or its pharmaceutically acceptable salt in an effective amount.EFFECT: produced are the new compounds of formula IA or IB possessing sGC-stimulating activity.58 cl, 6 tbl, 12 ex

Prodrug of triazolone compound // 2581369
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a new compound of formula (I) or its pharmaceutically acceptable salt possessing the properties of blood coagulation inhibitor. In the compound of formula (I) , R1 represents 1) phenyl optionally substituted by one to three C1-C6alkyl groups, 2) C1-C6alkoxy or 3) C2-C6alkenyloxy; R2 represents a hydrogen atom, C1-C6alkylcarbonyl or pyridylcarbonyl; each of R3 and R4 independently represents a hydrogen atom or C1-C6alkyl; A represents a single bond, oxygen atom, or a group presented by formula (II) , wherein each of Ra and Rb independently represents a hydrogen atom or C1-C6alkyl, whereas *1 and *2 mean a binding to carbonyl and R5, respectively, in formula (I), or a group presented by formula (III) , wherein each of Rc, Rd, Re and Rf independently represents a hydrogen atom or C1-C6alkyl, whereas *1 and *2 are characterised by the same values described above; and R5 represents C1-C6alkyl or C3-C8cycloalkyl, whereas C1-C6alkyl or C3-C8cycloalkyl in R5 is independently substituted by one to three identical or different substitutes specified in a group of substitutes consisting of a halogen atom, C1-C6akyl and C1-C6alkoxy.EFFECT: compounds can find application in the diseases caused by thrombus formation, such as thrombosis, deep-vein thrombosis, pulmonary embolism, cerebral infarction, myocardial infarction, acute coronary syndrome, vascular restenosis, disseminated intravascular coagulation, or malignant tumour.16 cl, 6 dwg, 5 tbl, 68 ex

Substituted benzoazepines as toll-like receptor modulators // 2580320
FIELD: chemistry.SUBSTANCE: invention relates to formula compounds, where Y stands for 6-membered heteroaryl, containing 1-2 nitrogen atoms; R2 is selected from OR14 and NR6R7; each of R6 and R7 is independently selected from H, C1-C12 alkyl, C3-C12 cycloalkyl, 6-membered heterocycle, containing 1 nitrogen atom, or benzyl, where said alkyl, cycloalkyl or benzyl are optionally substituted with one or more groups, independently selected from -F, -OR8, -NR12SO2R13, -C(=O)NR12R13, or R6 and R7, together with nitrogen atom, which they are bound to, form 5-6-membered heterocylic ring, containing 1 nitrogen atom, and said 5-6-membered heterocyclic ring is optionally substituted with one or more -OH; R8 is selected from hydrogen and C1-C12 alkyl, and each of R12, R13 and R14 is independently selected from H and C1-C12 alkyl, where said alkyl is optionally substituted with -OH; or their tautomers, enantiomers or pharmaceutically acceptable salts. The invention also relates to particular derivatives of benzo[b]azepine, given on i. 3, to set for treating TLR7- and/or TLR8-mediated condition, pharmaceutical composition and methods for treating TLR7- and/or TLR8-mediated conditions.EFFECT: derivatives, possessing agonistic activity with respect to TLR7 or TLR8 receptor.14 cl, 3 tbl, 222 ex

Pesticidal arylpyrrolidines // 2578720
FIELD: chemistry.SUBSTANCE: in formula (I) R1 is C1-12 haloalkyl, R2 is oxo and n equals 1 or 2, if the dotted line in formula (I) denotes a bond, such that R2 is linked through a double bond to the pyrrolidine ring; or R2 is hydroxy, n equals 1, if the dotted line in formula (I) is of no importance, such that R2 is linked through a single bond to the pyrrolidine ring; A is C-X3 or nitrogen; X1, X2, X3 and X4 each independently denote hydrogen, halogen, C1-12 alkyl, C1-12 haloalkyl, B1 is C-Y1 or nitrogen; B2 is C-Y2; B3 is C-Y3; B4 is C-Y4 or nitrogen; or B3, B4 and the bond between B3 and B4 together denote sulphur; Y1, Y2, Y3, and Y4 each independently denote hydrogen, halogen, cyano, C1-12 alkyl, C1-12 haloalkyl, C3 cycloalkyl, C1-12 alkoxy, C1-12 haloalkoxy, C6 aryl or a 6-member heterocyclyl containing one N atom as a heteroatom. The values of the radicals G, (Z), I, W, R3, R5-R7, m are given in the claim. The invention also relates to a method of producing the said compounds and to the use of the compounds for insect and spider control.EFFECT: invention relates to arylpyrrolidine derivatives of structural formula which can be used as insecticides and acaricides.15 cl

Aminoalkylpyrimidine derivatives as histamine h4 receptor antagonists // 2573828
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new aminoalkylpyrimidine derivatives of formula (I) or their pharmaceutically acceptable salts exhibiting the properties of histamine H4 receptor antagonists. The compounds are applicable in respiratory diseases, including asthma, allergic rhinitis, chronic obstructive pulmonary disease (COPD); ophthalmic diseases, including conjunctivitis, dry eye syndrome, cataract; dermatological diseases, including eczema, dermatitis (e.g., atopic dermatitis), psoriasis, urticaria, pemphigus, dermatitis herpetiformis, cutaneous vasculitis, itch; inflammatory intestinal diseases, including nonspecific ulcerative colitis, Crohn's disease; and autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, cutaneous lupus, systemic lupus erythematosus, widespread vasculitis and graft rejection. In formula IR1 and R2 form together with N atom to which they are bound, a saturated heterocyclic group containing one nitrogen atom and free frpm any other heteroatoms; the above heterocyclic group is substituted by one -NRaRb group and optionally substituted by one or more C1-4alkyl groups; wherein the heterocyclic group represents a 4-7-merous monocyclic group; Ra represents H or C1-4alkyl; Rb represents H or C1-4alkyl; R3 represents H or C1-8alkyl; R4 represents a) C1-8alkyl optionally substituted by one or more halogens; b) C3-10cycloalkyl-C0-4alkyl; c) aryl-C0-4alkyl or d) 5-6-merous heteroaryl-C0-4alkyl, wherein the radicals b), c) or d) may be substituted as specified in the patent claim; n equals to 1 or 2; each R5 independently represents H or C1-8alkyl.EFFECT: compounds can find application in treating or preventing an allergic, immune system or inflammatory disease, pain or cancer.22 cl, 18 ex

Azole derivative // 2573634
FIELD: medicine.SUBSTANCE: invention relates to compound of structural formula (1), which possesses inhibiting activity with respect to rotamase «FKBP12». In formula R1 represents formulae or X represents -(CH2)m-X1-(CH2)n-; X1 represents bond, -O-, -NRaC(=O)-, -C(=O)NRb-, -NRcS(=O)2- or -S(=O)2NRd-; Ra, Rb, Rc and Rd, each can be similar or different and represent hydrogen atom or C1-6alkyl group; m and n, each, can be similar or different and represent integer number 0-3; R2 represents phenyl group, pyridyl group, pyridazyl group, pyrimidyl group or pyrazinyl group. Values of ring A radical and substituents of R2 radical are disclosed in invention formula. Invention also relates to pharmaceutical preparation, which contains claimed compound, and to medication for prevention of treatment of alopecia.EFFECT: increase of treatment efficiency.12 cl, 3 dwg, 1 tbl, 24 ex

Arylethinyl derivatives // 2573560
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a new ethinyl derivative of formula I in the form of a racemic mixture or respective enanthiomer and/or optic isomer and/or stereoisomer or to a pharmaceutically acceptable salt of the above compounds formed by acid addition. The compounds are allosteric modulators of metabotropic glutamate receptor subtype 5 (mGluR5) and can find application in treating diseases mediated by mGluR5 action, wherein a disease is schizophrenia, cognitive disorders, fragile X syndrome or autism. In formula I , U is N or C(R5); V is CH or N; W is CH or N; provided only one of the groups U, V or W is a nitrogen atom, R5 is hydrogen, methyl or halogen; Y is -N(R6)-, -O-, -C(R7')(R7)-, -CH2O- or -CH2S(O)2-; R6 is hydrogen or lower alkyl, whereas R7/R7' independently represent hydrogen, hydroxy group, lower alkyl or lower alkoxy group; R1 is phenyl or 5-6-merous heteroaryl containing 1-2 heteroatoms specified in nitrogen atoms, which can contain one or two substitutes specified in halogen or lower alkyl; R2/R2' independently represent hydrogen, lower alkyl, hydroxy group, lower alkoxy group, C3-C6-cycloalkyl, CH2-lower alkoxy group, or together with a carbon atom, to which they are attached, can form C3-C6-cycloalkyl, or a ring containing -CH2OCH2-; m is equal to 0, 1 or 2; if m is equal to 1, R3/R3' independently represent hydrogen, lower alkyl, CH2-lower alkoxy group, or together with a carbon atom, to which they are attached, can form C3-C6-cycloalkyl; or R3 and R2 together with a carbon atom, to which they are attached, can form C3-6-cycloalkyl or a ring containing -(CH2)2OCH2-; n is equal to 0 or 1; if n is equal to 1, R4/R4' independently represent hydrogen, lower alkyl, CH2-lower alkoxy group or together with a carbon atom, to which they are attached, can form C3-C6-cycloalkyl; R4 and R2 together with a carbon atom, to which they are attached, can form C3-6-cycloalkyl; or if n is equal to 0, and Y is -N(R6)-, then R6 and R2 together with a carbon atom and a nitrogen atom, to which they are attached, can form C3-6-cycloalkyl; if n and m are equal to 0, then R2 and R7 with a carbon atom, to which they are attached, can form C3-6-cycloalkyl.EFFECT: producing the compounds mediated by mGluR5 action.28 cl, 1 tbl, 174 ex

Novel heterocycles // 2572616
FIELD: medicine.SUBSTANCE: invention relates to application of formula (I) compound, for preparation of medication, used for treatment of chronic obstructive pulmonary disease. In compound (I) A represents aryl group, selected from phenyl; B represents aryl group, selected from phenyl or pyridyl; X represents carbon atom or nitrogen atom; R represents substituted or non-substituted groups, selected from heteroaryl groups, including pyridyl, thienyl, furyl, pyrrolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyrimidinyl and pyrazinyl, and heterocyclic groups, including morpholine, thiomorpholine, piperazine, piperidine, piperidin-4-one, pyrrolidine, pyrrole-2,5-dione, thiazolidine, 1-oxido-thiazolidine and 1,1-dioxido-1,3-thiazolidine; where heterocyclic group is optionally substituted with substituents, independently selected from substituted or non-substituted (C6)aryl, -CH2-C6aryl, -CH2-heteroaryl, CO-C6aryl, -CO-heteroaryl, -CS-heteroaryl, -CO-C3-6cycloalkyl, cyano(C1-4)alkyl, -O-methyloxime, -SO2Cl, formyl, or other substituted or non-substituted heterocyclic group, selected from pyridyl, pyrimidinyl and piperidinyl; where binding of heterocyclic group to pyrimidine ring takes place through carbon or nitrogen atom; and where group R or substituent of heterocyclic group R are optionally substituted. Other substituents are given in invention formula.EFFECT: compounds are suitable for treatment of immunological diseases, inflammation, pain impairment, rheumatoid arthritis; osteoporosis, multiple myeloma, uveitis, acute and chronic myelogenous leukaemia; atherosclerosis, cancer, cachexia and other diseases.15 cl, 15 tbl, 158 ex

Antiviral heterocyclic compounds // 2572558
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new compounds of formula (I), which possess the properties of HCV NS5B RNA-polymerase inhibitor. The compounds may be used for treating or preventing an infection caused by hepatitis C virus (HCV). In formula (I), X represents CH or N, R1 is specified in a group consisting of R1a, R1c: wherein R1a is optionally substituted by C1-6alkyl, C1-6alkoxy or hydroxy, and wherein R1c is optionally substituted by C1-6alkyl; R2 represents (a) aryl specified in phenyl, or (b) NRaRb, wherein the above aryl is optionally substituted by (CH2)nNRcRd; Ra and Rb together with a nitrogen atom, to which they are attached, represent 5-merous heterocyclic amine substituted by (CH2)nNRcRd group, wherein n means a number from zero to two; Rc and Rd independently represent hydrogen, O2SR4, wherein R4 represents C16alkyl; R3 represents CR4aR4bR4c, wherein: 1) R4a, R4b and R4c are independently specified in C1-3alkyl.EFFECT: producing the compounds for treating or preventing an infection caused by hepatitis C virus (HCV).14 cl, 2 tbl, 9 ex
 
2551382.
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