Linked by a carbon chain containing aromatic rings (C07D401/10)

C   Chemistry; metallurgy(318327)
C07   Organic chemistry(61593)
C07D401/10                     Linked by a carbon chain containing aromatic rings(99)
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

Casmylate salt // 2638175
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely, to camsylate salt of (1r,1'R,4R)-4-methoxy-5"-methyl-6'-[5-(prop-1-yn-1-yl)pyridin-3-yl]-3'H-dispyro[cyclohexane-1,2'-indene-1'2'-imidazole]-4"-amine. The invention also relates to a pharmaceutical composition comprising this salt and a method of treatment based on the use of said camsylate salt. .EFFECT: new salt is produced, useful in the treatment of Aβ pathologies, such as Alzheimer's disease, Down's syndrome, β-amyloid angiopathy.10 cl, 1 dwg, 2 tbl, 7 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
Aminopyridine derivatives as modulators of leucine-rich repeated kinase 2 (lrrk2) // 2634716
FIELD: pharmacology.SUBSTANCE: compounds are designed to treat a disease such as Parkinson's disease, in particular hereditary Parkinson's disease. In formula I, m is from 0 to 1; -NRa-; -O-; or -S(O)r- where r is from 0 to 2 and RA is hydrogen; R1 is C1-6-alkyl; R2 is halogen; cyano; or halo-C1-6-alkyl; R3 and R4 are independently halogen; C1-6-alkyl; C1-6-alkoxy; halo-C1-6-alkyl; or halo-C1-6-alkoxy; or R3 and R4 together with the atoms to which they are attached, can form a five- or six-membered ring which optionally includes one or two heteroatoms independently selected from O; and R5 is C1-6-alkylsulfonyl; or cyano.EFFECT: increased efficiency of treatment.17 cl, 3 tbl, 32 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
Compound as wnt signal inhibitor, its compositions and application // 2627712
FIELD: pharmacology.SUBSTANCE: invention relates to a heterocyclic compound of the general formula (I) or an N-oxide thereof, wherein X1, X2, X3 and X4 independently represent CR4 or N, where 0 or 1 of X1-X4 can be N; Y1, Y2 and Y3 are hydrogen; R1 is selected from hydrogen, , C6 aryl, 6-member heterocycloalkyl containing 2 heteroatoms selected from N and O, and 5- or 6-member heteroaryl containing 1-4 heteroatoms selected from N, O and S, wherein each of C6 aryl, 6-member heterocycloalkyl and 5- or 6-member heteroaryl may be optionally substituted with one R4; R2 is selected from hydrogen, halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl and 6-member heteroaryl may be optionally substituted with one R4. If X5 is N, R2 is selected from halogen, C1-6 alkyl, , C6 aryl and 6-member heteroaryl containing 1 to 2 N atoms, where each of C6 aryl, and 6-member heteroaryl may be optionally substituted with one R4; each R4 Is independently selected from hydrogen, halogen, cyano, oxo, C1-6 alkoxy, -C(O)OR5, -C(O)R5, C1-6 alkyl. Moreover , C1-6 alkyl may be optionally substituted with 1 to 3 substituents selected from halogen and cyano; R5 is C1-6 alkyl; and where the central structure of Formula I, limited by X5, X6, X7 and X8, is: or The invention also relates to particular compounds, a method for inhibiting the secretion of WNT signalling in a cell, use of a compound of formula (I), a method for treatment of a disorder mediated by WNT. .EFFECT: new heterocyclic compounds have been obtained that are useful for treatment of cancer, fibrosis and osteoarthritis.22 cl
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

New derivatives of 3,3-dimethyltetrahydroquinoline // 2603276
FIELD: chemistry.SUBSTANCE: invention is related to organic chemistry and specifically to new tetrahydroquinolin derivatives of general formula (I) or pharmaceutically acceptable salts or esters where R1 represents hydrogen, halogen, carboxyl, alkoxycarbonyl, alkilsulphonylaminocarbonyl or cycloalkylalkilsulphonylaminocarbonyl; R2 represents hydrogen, halogen or carboxyl; R3 represents hydrogen, halogen, carboxyl, halogenalkyl, cyano, alkoxycarbonyl, alkylsulphonyl, alkylsulphonylaminocarbonyl, cycloalkylalkilsulphonylaminocarbonyl, carboxylalkylamino(alkyl)carbonyl, alkyl(hydroxy)pyrrolidinylcarbonyl or carboxylpyrrolydincarbonyl; R4 is hydrogen, carboxyl, alkilsulphonylaminocarbonyl or cycloalkylalkilsulphonylaminocarbonyl; R5 is pyridinyl, substituted pyridinyl, morphonylpyrinidil, phenyl or substituted phenyl, where substituted pyridinyl and substituted phenyl represent pyridinyl and phenyl, substituted with one or two substitutes given in the patent claim; where the alkyl, one or in combination, is saturated alkyl group with linear or branched chain containing 1 to 6 carbon atoms; alkoxy, one or in combination, denotes a group of alkyl-O-, where the alkyl such as defined above; cycloalkyl, one or in combination, relates to saturated carbon ring, containing from 3 to 6 carbon atoms; provided that 3,3-dimethyl-2-phenyl-1,2,3,4,6-hydroxyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinline is excluded. Invention is also related to specific compounds, pharmaceutical composition based on compound of formula (I), use of formula (I) and a method of treating or preventing diseases based on use of compounds of formula (I).EFFECT: technical result is obtaining novel tetrahydroquinolin derivatives, useful as activator AMR-activated protein kinase (AMPK).17 cl, 236 ex

Uracil or thymine derivatives for treating hepatitis c // 2599635
FIELD: chemistry.SUBSTANCE: invention relates to a compound of N-(6-(3-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-methoxyphenyl)naphthalene-2-yl)methanesulfonamide or its pharmaceutically acceptable salt for use as a medicinal agent for inhibiting replication of hepatitis C virus (HCV), as well as to a medicinal agent containing a therapeutically effective amount of the said compound or its pharmaceutically acceptable salt.EFFECT: technical result is stable indices of efficiency of treating, relieving symptoms of hepatitis C, providing partial or complete reduction of symptoms.5 cl, 46 dwg, 40 tbl, 140 ex

New substituted quinoline compounds as inhibitors of s-nitrozoglutation-reductase inhibitors // 2599144
FIELD: chemistry.SUBSTANCE: invention is related to organic chemistry and specifically to novel quinoline derivatives of general formula I or pharmaceutically acceptable salts, stereoisomers or N-oxides, where m = 0 and 1; R1 is independently selected from a group consisting of chlorine, fluorine and bromine; R2b and R2 c are independently selected from a group, consisting of hydrogen, halogen, C1-C3 alkyl, fluorinated C1-C3alkyl, cyano and N (CH3)2; X is selected from a group consisting of n is selected from a group consisting of 0 and 1; R3 is independently selected from a group consisting of halogen, C1-C3 alkyl, fluorinated with1-C3 alkyl, cyano, C1-C3alkoxy and NR4R4′, where R4 and R4′ are independently selected from a group consisting of C1-C3 alkyl; and a is selected from a group consisting of .Invention is also related to the use of formula I, pharmaceutical composition based on the compound of formula I, method of treating pulmonary disorders and inflammatory diseases based on use of the compound of formula I, and a method of producing a pharmaceutical composition based on the compound of formula I.EFFECT: technical result is obtaining novel quinoline derivatives, useful as inhibitors of S-nitrozoglutation reductase (GSNOR).17 cl, 64 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

Guanidine compounds and compositions for inhibiting nampt // 2593759
FIELD: chemistry. SUBSTANCE: invention relates to a compound of formula II: , where Ar1 represents a 6-10-member heteroaryl, where heteroaryl relates to a monocyclic or bicyclic heteroaryl containing 1, 2 or 3 heteroatoms selected from N, S or O, provided that two adjacent heteroatoms in ring can not both represent S or both represent O; Ar2 is phenyl; R1 is phenyl, 5-12-member heterocycloalkyl or 5-12-member heteroaryl (i), where each of said phenyl, heterocycloalkyl and heteroaryl is either unsubstituted or optionally independently substituted with 1, 2, 3, 4 or 5 substitutes, which can be identical or different and are independently selected from a group consisting of: halogen, cyano, alkyl, halogenalkyl, alkoxy, halogenalkoxy, -NRaRb, -CONaRb, -S(O)2-alkyl,-S(O)2N(alkyl)2, -(CH2)qaryl, -(CH2)qheteroaryl and -(CH2)qheterocycloalkyl, (ii) where each of said phenyl can further be unsubstituted or substituted with one or more substitutes, such as halogen, cyano, alkyl or alkoxy, or can be optionally condensed with independently selected arylheteroaryl or heterocycloalkyl; Ra and Rb independently represent H, alkyl,-S(O)2alkyl and cycloalkyl, or Ra and Rbcan form a 5- or 6-member heterocycloalkyl group together with a nitrogen atom to which they are bonded, where said heterocycloalkyl group may contain one or more additional heteroatoms selected from N, S or O; (iii) said 5-12-member heterocycloalkyl contains 1, 2 or 3 heteroatoms selected from N, S or O; (iv) said 5-12-member heteroaryl contains 1, 2 or 3 heteroatoms selected from N, S or O; R2 and R3 represent H, m, n, p and q independently are equal to 0, 1 or 2; and their pharmaceutically acceptable salts. EFFECT: compounds can be used to inhibit NAMPT. 29 cl, 3 tbl, 5 ex

Substituted benzoazepines as modulators of toll-like receptors // 2593261
FIELD: chemistry. SUBSTANCE: invention relates to a compound of formula I or tautomer, enantiomer or pharmaceutically acceptable salt thereof, where said formula Y represents -(O)x(CH2)yR11; x is selected from 0 and 1; y is selected from 0, 1, 2, and 3; R11 is selected from phenyl, pyridyl, morpholinyl, 1-oxo-1,3-dihydroisobenzofuranyl and 2-oxo-tetrahydrofuranyl, when x equals 0, said phenyl or pyridinyl substituted -C(O)NR1R2 or T; R1 and R2 is selected independently from hydrogen and C1-6alkyl, wherein said alkyl is optionally substituted -C(O)O(CH2)tR12, or R1 and R2 together with a nitrogen atom to which they are bonded, form a saturated 5-member heterocycle containing 1-4 heteroatoms selected from nitrogen, oxygen and sulphur; t is selected from 0, 1, 2, and 3; R12 is selected from C3-6cycloalkyl and phenyl; T is selected from 2-oxo-1,3-dioxolane, 2-oxotetrahydrofuran -(CHR7)zOR9, -(O)u(CH2)sC(O)R8, -OSO2R13 and -CH(OH)CH2OH; R7 represents H; R8 is -OR10; R9 represents H; R10 is selected from C1-6alkyl, -(CH(2)R12 and hydrogen, wherein said alkyl is optionally substituted with halogen or diC1-6alkylamine; R13 represents CF3; u is selected from 0 and 1; z is selected from 1, 2, and 3; s is selected from 1 and 2; R5 is selected from -NR3R4 and -OR10; R3 and R4 independently selected from H, C1-12alkyl, -(O)q(CH2)rP; said alkyl is optionally substituted with -OH; q is selected from 0 and 1; r is selected from 0, 1, 2, and 3; P is selected from phenyl, -SO2R6, piperidinyl and pirrolidinyl; and R6 is -NH2, provided that when R11 is a phenyl or pyridyl, then a) x+y ≥ 1; or b) R11 is substituted with T; or c) R5 is NR3R4, and at least one of R3 or R4 is -(O)q(CH2)rP-, and q+r ≥ 1; or d) at least one of R1 or R2 represents alkyl, substituted with -C(O)O(CH2)R12. Invention also relates to a pharmaceutical composition exhibiting TLR7- and/or TLR8 agonist activity, comprising an effective amount of a compound of formula I together with a pharmaceutically acceptable diluent or carrier. EFFECT: substituted benzoazepine exhibiting TLR7- and/or TLR8 agonist activity. 17 cl, 3 tbl, 47 ex

Catechol-o-methyl transferase inhibitors and use thereof in treating psychotic disorders // 2586974
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to derivatives of 4-pyridinone formula I or pharmaceutically acceptable salts thereof, where A is hydrogen, B(OH)2, halogen, C(O)NH(CH2)nC(O)N(R3)2; X is hydrogen or halogen; Y denotes phenyl, benzimidazolil, benztiazolil, benzoksazolil, benzpiperidinil, quinolyl, indolyl, indazolyl or pyridyl, each optionally substituted with 1-3 groups Ra, provided that Y denotes phenyl, then at least one of said Ra selected from OCF3, O(CH2)nC3-6cycloalkyl, NR2C(O)R2, C(O)R2, N(R2)2, (CH2)nC(O)OR2, OR2, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, (CH2)n(C)6-10aryl, O(CH2)nC6-10aryl or O(CH2)nheterocyclyl, where said heterocyclic ring and aryl optionally substituted with 1-3 groups Rb; R1 represents hydrogen, NR2R3, Si(CH3)3, (CH2)nC6-10aryl, C2alkenyl or C1-4alkyl, said alkyl and alkenyl optionally substituted with 1-3 groups of halogen, OH, C1-6alkyl, O-C1-6alkyl, NR2R3, SOR2, NHSO2R2, CF3, C6-10aryl, heterocyclyl, -C≡C-C6-10aryl, C(O)NR2R3, wherein said aryl and heterocyclyl optionally substituted with 1-2 groups Ra; R2 and R3 independently denote H, C1-6alkyl, (CH2)nheterocyclyl, (CH2)nC6-10aryl, wherein said aryl optionally substituted by group Ra or R2 and R3 together with nitrogen atom to which they are bonded, form a 6-member ring, which contains oxygen; Ra is C1-6alkyl, halogen, CF3, OCF3, C3-6cycloalkyl, O(CH2)nC3-6cycloalkyl, NR2C(O)R2, C(O)R2, CN, N(R2)2, (CH2)nC(O)OR2, OR2, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, (CH2)nC6-10aryl, O(CH2)nC6-10aryl or O(CH2)nheterocyclyl, wherein said heterocyclyl and aryl optionally substituted with 1-3 groups Rb; Rb is C1-6alkyl, halogen, CHF2, oxo (=O), N(R2)2, CH2OH, S(O)2NR2R3, (CH2)nC6-10aryl, (CH2)nheterocyclyl, NH(CH2)nheterocyclyl, OR2, C3-6cycloalkyl, CF3 or CN; and n equals 0-3; and where heterocycle is aromatic or saturated or partially saturated monocyclic or bicyclic ring containing 5-10 atoms, among which 1-4 atoms are heteroatoms selected from nitrogen, oxygen and sulphur. Invention also relates to pharmaceutical composition based on compound of formula I, method of treating and/or preventing neurological and psychiatric disorders and method of intensifying action of antipsychotic agent based on use of compound of formula I.EFFECT: new compounds are prepared effective in treating diseases associated with catechol-O-methyltransferase (COMT).52 cl, 1 tbl, 17 ex
Quinoline derivatives and melk inhibitors containing same // 2582610
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, namely to a heterocyclic compound of general formula (I) or its pharmaceutically acceptable salt thereof, where: R1 is C1-C6 alkyl sulphonyl or -CO-R5, where R5 is C1-C-6 alkyl or C3-C5 cycloalkyl; R2 represents phenyl which can contain group substitute selected from group of substitutes C, or -NR6AR7A, where R6A is hydrogen atom and R7A is -(CH2)n-R10A (where n equals whole number from 0 to 2 and R10A represents mono- or tricyclic C3-C10 cycloalkyl, which can contain group substitute selected from group of substitutes D, phenyl, which can contain group substitute selected from a group of substitutes E, aliphatic heterocyclic group which is selected from piperidinil, piperazinil and azabicyclooctanil and can be substituted C1-C-6 alkyl, aromatic heterocyclic group which is selected from a pyridinyl, pyrimidinyl and pirazolil and can contain group substitute selected from a group of substitutes I), or R6A and R7A is formed with adjacent nitrogen atom aliphatic heterocyclic group that is selected from piperidinil and piperazinil and may contain group substitute selected from a group of substitutes F; R3 is C6-C10 aryl, which can contain group substitute selected from a group of substitutes G, or aromatic heterocyclic group which is selected from a pyridinyl, pyrimidinyl, tiofenil, isoxazolyl, pyrrolyl and pirazolil and can contain group substitute selected from a group of substitutes H; R4 is hydrogen atom or halogen; R is hydrogen atom or halogen; and R101 is hydrogen atom; where said substitutes C - I are one-three substitutes are given in claim. Invention also relates to pharmaceutical composition, an inhibitor of MELK, agent, which simulates the expression MELK, anticancer agent based on compounds of formula (I), method of treating and/or preventing diseases, which includes MELK overexpression, using compound of formula (I).EFFECT: obtained are novel heterocyclic compounds effective as anti-tumour agent.19 cl, 4 tbl, 1200 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

Derivatives of (4-methylsulphonylaminophenyl)-quinoline, useful in treatment of hepatitis c // 2572835
FIELD: chemistry.SUBSTANCE: invention relates to field of organic chemistry, namely to compound, selected from the group of N-{4-[7-tert-butyl-8-methoxy-5-(2-oxo-1,2-dihydro-pyridin-3-yl)-quinolin-2-yl]phenyl}-methanesulphonamide; N-{4-[7-tert-butyl-8-methoxy-5-(6-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-quinolin-2-yl]-phenyl}- methanesulphonamide; and N-{4-[7-tert-butyl-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-8-methoxy-quinolin-2-yl]-phenyl}- methanesulphonamide; or to its pharmaceutically acceptable salt. The invention also relates to application of said compound for treatment or prevention of infection with hepatitis C virus (HCV) and for manufacturing thereof based medication.EFFECT: novel compounds, possessing useful biological activity have been obtained.5 cl, 2 tbl, 6 ex

1,2,4-triazolone derivative // 2566754
FIELD: chemistry.SUBSTANCE: invention relates to 1,2,4-triazolone derivatives and pharmaceutically acceptable salts thereof. The disclosed compounds have antagonistic activity with respect to the arginine vasopressin V1b receptor. In formula (IA): R1 is C1-5 alkyl (the C1-5 alkyl is optionally substituted with 1-3 groups selected from a group consisting of hydroxy, halogen atoms, and C3-7 cycloalkyl), C3-7 cycloalkyl or a 4-8-member saturated heterocycle, containing one heteroatom selected from an oxygen atom; R2 is a hydrogen atom; R3 is a phenyl or pyridyl (the phenyl or pyridyl is optionally substituted with 1 or 2 groups selected from a group consisting of C1-5 alkoxy, halogen atoms, cyano and C1-5 alkylsulphonyl); R4 and R5 can be identical or different, and each is a hydrogen atom or C1-5 alkyl (the C1-5 alkyl is optionally substituted with one hydroxy), or R4 and R5 optionally, together with a nitrogen atom with which they are bonded, form a 4-8-member saturated or unsaturated heterocycle, optionally containing one nitrogen, oxygen or sulphur atom, in addition to the nitrogen atom with which they are bonded, in a ring (the 4-8-member saturated or unsaturated heterocycle is optionally substituted with one or two groups selected from a group consisting of hydroxy, C1-5 alkyl ( the C1-5 alkyl is optionally substituted with one hydroxy), C1-5 alkoxy, halogen atoms, cyano, C2-5 alkanoyl, aminocarbonyl, trifluoromethyl and amino (the amino is optionally substituted with one or two groups selected from a group consisting of C1-5 alkyl and C2-5 alkanoyl), and the 4-8-member saturated heterocycle optionally has a C1-5 alkylene group which crosslinks two different carbon atoms in the ring, or form 2-oxa-6-azaspiro[3.3]hept-6-yl or 7-oxa-2-azaspiro[3.5]non-2-yl; A is phenylene, pyridinediyl or pyrimidinediyl (the phenylene, pyridinediyl and pyrimidinediyl are optionally substituted with one group selected from halogen atoms and C1-5 alkoxy); X is a single bond or -O-; Ra is a hydrogen atom or a C1-5 alkyl and n equals 0 or 1. The invention also relates to 1,2,4-triazolone derivatives, the structural formulae and values of radicals of which are given in the claim, to a pharmaceutical composition and to a therapeutic or preventive agent containing a 1,2,4-triazolone derivative or a pharmaceutically acceptable salt thereof.EFFECT: improved properties.12 cl, 16 tbl, 250 ex

ethod of obtaining 5-(1,5,3-dithiazepan-3-yl)quinoline and its application as means with fungicidal activity // 2565783
FIELD: chemistry.SUBSTANCE: invention relates to method of obtaining5-(1,5,3-dithiazepan-3-yl)-quinoline consisting in interaction of 5-aminoquinoline and 1-oxa-3,6-dithiacycloheptane in ethanol-chloroform medium (1:1, volume) in presence of catalyst Sm(NO3)3·6H2O with molar ratio 5-aminoquinoline : 1- oxa-3,6-dithiacycloheptane : Sm(NO3)3·6H2O = 1:1:(0.03-0.07) at room temperature (~20°C) and atmospheric pressure for 2.5-3.5 h. Invention also relates to application of compound (1) as fungicide against Rhizoctonia solani.EFFECT: method of obtaining compound of formula, possessing fungicidal activity, has been elaborated.2 cl, 2 tbl, 1 ex

Catechol-o-methyltransferase inhibitors and thereof application for treatment of psychotic disorders // 2563634
FIELD: chemistry.SUBSTANCE: invention relates to 4-pyridinone compounds of formula I: , where Y represents CN, C2-6-alkinyl, (CH2)nC5-10-heterocyclyl, (CH2)nC6-10-aryl, with said alkinyl, heterocyclyl and aryl being substituted with 1-3 groups Ra; X, X1 and R1 independently represent hydrogen, halogen, CN, C1-6-alkyl, with said alkyl being optionally substituted with 1-3 groups Ra; R2 represents H, OH, C1-6-alkyl, (CH2)nC3-10-cycloalkyl, (CH2)nC5-10-heterocyclyl, (CH2)nC6-10-aryl, with said aryl and heterocyclyl being optionally substituted with 1-3 groups Ra; Ra represents C1-6-alkyl, halogen, CF3, OCF3, NR2C(O)R2, C(O)N(R2)2, C(O)R2, CN, NHSO2R2, OR2, (CH2)nC5-10-heterocyclyl, (CH2)nC6-10-aryl, with said alkyl, heterocyclyl and aryl being optionally substituted with 1-3 groups Rb; Rb represents halogen; and n represents integer number from 0 to 2, which are catechol-O-methyltransferase (COMT) inhibitors.EFFECT: obtaining 4-pyridinone compounds.14 cl, 1 tbl, 16 ex

Quinolone compound and pharmaceutical composition // 2544530
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to organic chemistry, namely to new quinolin-4-one derivatives of formula (1) or to its pharmaceutically acceptable salt, wherein R1 represents: (1) hydrogen, (2) C1-C6 alkyl, (35) carbamoyl-C1-C6 alkyl optionally containing morpholinyl-C1-C6 alkyl, or (36) phosphonoxy-C1-C6 alkyl optionally containing one or two C1-C6 alkyl groups on a phosphonoxy group; R2 represents: (1) hydrogen or (2) C1-C6 alkyl; R3 represents phenyl, thienyl or furyl, wherein a phenyl ring presented by R3, can be substituted by one C1-C6 alkoxy group; R4 and R5 are bound to form a group presented by any of the following formulas: , , , , , , or a group presented by the following formula: a group optionally containing one or more substitutes specified in a group consisting of C1-C6 alkyl groups and oxogroups; R6 represents hydrogen; and R7 represents C1-C6 alkoxy group. The invention also refers to a pharmaceutical composition based on the compound of formula , to a preventive and/or therapeutic agent based on the compound of formula (1), using the compound of formula (1), a method for preparing the compound of formula , as well as to specific compounds.EFFECT: there are prepared new quinolin-4-one derivatives effective in treating neurodegenerative diseases, diseases caused by neurological dysfunction, or diseases caused by mitochondrial dysfunction.18 cl, 1 tbl, 257 ex

Uracyl and thymine derivatives for treating hepatitis c // 2543620
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

Bruton's tyrosine kinase inhibitors // 2542585
FIELD: medicine.SUBSTANCE: present invention refers to compounds having formula III such as below, wherein: Q represents C(Y3) or N; R represents H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 represents heteroaryl or heterocyclyl each of which is optionally substituted by one or more C1-6alkyls, hydroxyC1-6alkyls, oxogroups or halogenC1-6alkyls; R2 represents -C(=O), -O, -C(R2')2, -C(R2')2C(=O), -C(R2')2C(=O)NR2', C(R2')2 N(R2')C(=O), -C(=NH), -C(R2')2NR2' or -S(=O)2; each R2' independently represents H or C1-6alkyl; R3 represents H or R4; R4 represents C1-6alkyl, C1-6alkoxygroup, aminogroup, C1-6alkylaminogroup, di(C1-6alkyl)aminogroup, heterocyclyl, C1-10alkylheterocycloalkyl, heterocycloalkylC1-10alkyl each of which is optionally substituted by one or more C1-6alkyls, C1-6alkylaminogroups, di(C1-6alkyl)aminogroups, hydroxygroups, hydroxyC1-6alkyls, C1-6alkoxygroups, oxogroups or halogenC1-6alkyls; X represents CH; X' represents CH; and the rest symbols have values as specified in the patent claim. The compounds of formula III inhibit Bruton's tyrosine kinase (Btk). There are also described compositions containing the compounds of formula III, and at least one carrier, thinner or excipient, and a method for producing the compound of formula X in accordance with the following procedure.EFFECT: compositions are effective for modulating Btk activity and treating diseases related to Btk hyperactivity, and can be used for treating inflammatory and autoimmune diseases related to disturbed B-cell proliferation, such as rheumatoid arthritis.22 cl, 2 tbl, 260 ex

N-phenyl-dioxox-hydropyrimidine used as hepatitis c virus inhibitor (hcv) // 2542099
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

Bicyclic nitrogen-containing heterocyclic compounds, useful in treatment of hepatitis c // 2540332
FIELD: chemistry.SUBSTANCE: invention relates to field of organic chemistry, namely to novel heterocyclic compounds of general formula (I) or to their pharmaceutically acceptable salts, where X1 stands for N and X2, X3 and X4 stand for CR5; or X1 and X2 stand for N and X3 and X4 stand for CR5; or X1, X2 and X4 stand for CR5, and X3 stands for N; or X1, X2, X3 and X4 stand for CR5; R1 stands for (a) heteroaryl radical, selected from the group, including pyridinyl, 2-oxo-1,2-dihydropyridin-3-yl, 2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl, said heteroaryl optionally contains as substituents halogen, C1-C6-alkyl, C1-C6-hydroxyalkyl, C1-C3-alkoxy-C1-C3-alkyl, C1-C6-alkoxygroup, or (b) heterocyclic radical, selected from the group, including 2-oxotetrahydropyrimidin-1-yl, 2,6-dioxotetrahydropyrimidin-1-yl, 2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl and 2,4-dioxotetrahydropyrimidin-1-yl; R2 stands for hydrogen or C1-C6-alkoxygroup; R3 stands for (a) phenyl, (b) pyridine, where said phenyl or said pyridine independently optionally contain 1-3 substituents, selected from the group, including halogen, (CH2)nNRcRd, or (c) NRaRb, (d) hydrogen, (e) halogen; Ra and Rb together with nitrogen atom, which they are bound to, form cyclic amine, containing from 3 to 5 carbon atoms, independently substituted with group (CH2)nNReRf; Rc and Rd independently stand for hydrogen, SO2R8, where R8 stands for C1-C6-alkyl; Re and Rf independently stand for hydrogen, SO2R8, where R8 stands for C1-C6-alkyl; R4 stands for CF3, CH2CF3 or CR4aR4bR4c, where (i) R4a, R4b and R4c are independently selected from the group, including C1-C3-alkyl, CD3; or (ii) taken together R4a and R4b form C2-C4-alkylene and R4c stands for cyanogroup or C1-C2-fluoroalkyl; R5 in each case independently stands for hydrogen, halogen, C1-C6-alkoxygroup or C1-C6-alkyl; n in each case independently equals 0-3. Invention also related to method of treating infection with hepatitis C virus, method of inhibiting HCV replication, application of formula (I) compound and based on it pharmaceutical composition.EFFECT: novel heterocyclic compounds of formula (I), possessing useful biological activity are obtained.24 cl, 3 tbl, 43 ex

Pyrimidines applicable as anti-infectious agents, and applications thereof // 2539570
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

Compound with successive aricyclic structure, possessing activity of inhibiting acycloenzyme a diacylglycerolacyltransferase (dgat1) // 2538964
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

Benzimidazole and imidazo[4,5-c]pyridine derivatives as hedgehog pathway antagonist // 2533825
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to organic chemistry, namely to a heterocyclic compound of formula I and its pharmaceutically acceptable salt, wherein if a chemical valency permits, i represents 1 or 2, R1 represents H; a linear (C1-C4) alkyl group, R2 represents H, Cl or F, X represents either N, or CR3, R3 represents H; halogen; a linear (C1-C4) alkyl or (C1-C4) alkoxyl group, Y represents Z represents O or NRx, Rx represents H or a linear or branched (C1-C4) alkyl, k is equal to 2, 3 or 4, n and p independently represents 2, and a sum of n+p cannot exceed 4, T represents H or a linear (C1-C4) alkyl group; T′ represents a linear C1-C3 alkyl chain substituted by either (C1-C6)-dialkylaminogroup, or a 5-6-merous saturated heterocycle containing one nitrogen atom and optionally containing the second heteroatom specified in O, such a heterocyclic ring is optionally substituted by a (C1-C4) alkyl chain at nitrogen atoms; or a 5-merous saturated heterocycle containing one nitrogen atom, such a heterocyclic ring is optionally substituted by a (C1-C4) alkyl chain at nitrogen atoms; r represents zero, 1; R′ represents di(C1-C4)alkylamino, (C1-C4)alkoxy; except for the compounds specified in the clause. The invention also refers to a pharmaceutical composition based on the compound of formula (I), using the compound of formula (I) and to a method of treating diseases, in which the hedgehog signalling pathway modulation is effective.EFFECT: there are prepared new heterocyclic compounds possessing t effective biological properties.20 cl, 193 ex

Iminopyridine derivatives and use thereof as microbiocides // 2532135
FIELD: chemistry.SUBSTANCE: invention relates to a method of controlling infection of useful plants with phytopathogenic microorganisms or prevention thereof, wherein a compound of formula I or a composition thereof, which contains said compound as an active ingredient, is deposited on plants, on a parts thereof or place where said plants grow, where the compound of formula I is substitutes are as defined in claim 1.EFFECT: obtaining a compound for controlling infection of useful plants with phytopathogenic microorganisms.26 cl, 2 tbl, 8 ex

New thyroid hormone beta-receptor agonist // 2527948
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to a new compound of formula [I] or to its pharmaceutically acceptable salt, wherein A represents optionally substituted alkyl, wherein the substitute represents identical or different 1-3 groups specified in aryl optionally substituted by 1-3 groups specified in alkyl, halogen, alkoxy and alkanoyl; cycloalkyl optionally substituted by 1-3 groups specified in alkyl and halogen; hydroxy; alkoxy; halogen; an amino group and oxo; an optionally substituted carbocyclic group specified in a mono- and bicyclic group, wherein an aromatic ring and cycloalkyl are condensed; optionally substituted aryl, an optionally substituted completely saturated 5- or 6-merous monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, wherein the substitute of optionally substituted aryl, the optionally substituted carbocyclic group and the optionally substituted heterocyclic group for A represents identical or different 1-3 groups specified in alkyl, optionally substituted hydroxy, alkoxy, cycloalkyl or halogen; cycloalkyl optionally substituted by alkyl or alkoxy; alkoxy optionally substituted by halogen; halogen; hydroxy; oxo; heterocycle; alkyl sulphonyl; and mono- or dialkylcarbamoyl, optionally substituted amino, wherein the substitute represents identical or different 1 or 2 alkyl or aryl, or optionally substituted carbamoyl, wherein the substitute represents identical or different 1 or 2 alkyls optionally substituted by aryl, X represents optionally substituted methylene or -O-, wherein the substitute of optionally substituted methylene for X represents alkoxy or hydroxy, Q represents N or C-R4, L1 represents a single bond, methylene, -CH=CH-, -O-, -CO-, -NR11-, -NR11CO-, -CONR11- or -CH2NR11-, L2 represents a single bond, -CR6R7- or a bivalent 5- or 6-merous completely saturated monocyclic heterocyclic group each of which contains 1 heteroatom specified in nitrogen and oxygen, R1 and R2 are identical or different, and each represents hydrogen, alkyl or halogen, R3 and R4 are identical or different, and each represents hydrogen, alkyl, alkoxy, cyano or halogen, R1 and R3 are optionally bond thereby forming 5- or 6-merous cycloalkane, or a 5- or 6-merous aliphatic heterocycle containing oxygen atom, R5 represents a carboxyl group, an alkoxycarbonyl group or a bioisosteric group of the carboxyl group, R6 and R7 are identical or different, and each represents hydrogen or alkyl, or R6 and R7 are bond thereby forming cycloalkane, R8 represents hydroxy, alkanoylamino or alkyl sulphonylamino, R9 and R10 represent hydrogen or halogen, and R11 represents hydrogen or alkyl. Besides, the invention refers to specific compounds of formula [I], a drug based on the compound of formula [I], using the compound of formula [I], a method of treating based on using the compound of formula [I], and an intermediate compound of formula [II].EFFECT: there are prepared new compounds possessing the agonist activity on thyroid hormone β receptor.18 cl, 36 tbl, 344 ex

Pharmaceutical salt of 8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-1-cyclopropyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid, pharmaceutical composition containing same, medicinal agent and method of treating or preventing bacterial infections using said salts // 2515557
FIELD: chemistry.SUBSTANCE: present invention relates to a pharmaceutical salt of 8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-1-cyclopropyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid, characterised by that it is in form of a hydrochloride monohydrate and by solubility of at least 0.050 mg/ml water. The invention also relates to a pharmaceutical composition based on said pharmaceutical salt, use of said pharmaceutical salt and a method of treating or preventing bacterial infections based on use of said pharmaceutical salt.EFFECT: obtaining a novel pharmaceutical salt of 8-methyl-7-[5-methyl-6-(methylamino)-3-pyridinyl]-1-cyclopropyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid, characterised by good solubility in water, which influences bioavailability of the active ingredient.7 cl, 16 dwg, 2 tbl, 9 ex

Novel pyridinones and pyridazinones // 2505538
FIELD: chemistry.SUBSTANCE: invention relates to derivatives of 5-phenyl-1 H-pyridin-2-one and 6-phenyl-2H-pyridazin-3-one of general formulas I-III: , where: R represents H, -R1, -R1-R2-R3, -R1-R3 or -R2-R3; R1 represents heteroaryl, which stands for monocyclic radical, which contains 5-6 atoms in cycle and one or several heteroatoms N, optionally substituted by one or some lower alkyls; R2 represents -C(=O), -C(=O)NR2'; where R2' represents H or lower alkyl; R3 represents H or R4; where R4 represents lower alkyl or heterocycloalkyl, which stands for monovalent saturated cyclic radical, consisting of one ring, which contains one or two ring-shaped heteroatoms, selected from N and O; X represents CH or N; Y1 represents H, lower alkyl or lower halogenalkyl; each Y2 independently represents lower alkyl, which is optionally substituted by one or several substituents, selected from group, which consists of hydroxygroup, lower alkoxygroup; n has value 0, 1, 2 or 4; Y3 represents Y4a, Y4b, Y4c or Y4d; where Y4a represents H; Y4b represents lower alkyl, optionally substituted by one or sseveral substituents, selected from group, consisting of lower halogenalkyl, halogen; Yc represents lower cycloalkyl, optionally substituted by one or some substituents, selected from group, consisting of lower alkyl, lower halogenalkyl, halogen; and Y4d represents aminogroup, optionally substituted by one or some lower alkyls; or to its pharmaceutically acceptable salt. Also described are: pharmaceutical composition, based on upper said compounds, as well as application of compounds of I-III formulas for treatment of inflammatory or autoimmune condition.EFFECT: described are novel compounds, which can be useful for modulating Btk activity and treatment of diseases, associated with excess Btk activity.14 cl, 102 ex, 1 tbl

Novel substituted pyridin-2-ones and pyridazin-3-ones // 2500680
FIELD: chemistry.SUBSTANCE: invention relates to novel pyridin-2-one and pyridazin-3-one derivatives, having Btk inhibiting activity. In formulae I-IV: ,R denotes -R1-R2-R3 or -R2-R3; R1 denotes a heteroaryl containing 6 ring atoms, including one N heteroatom; R2 denotes -C(=O), -C(=O)N(R2'), where R2' denotes H; R3 denotes R4; where R4 is a lower alkyl, heterocycloalkyl, (lower alkyl) heterocycloalkyl or heterocycloalkyl (lower alkyl), where the heterocycloalkyl contains 6 ring atoms, including two heteroatoms selected from N and O; and where R4 can be substituted with one or more substitutes selected from lower alkyl, oxo group and lower alkoxy group; X denotes CH or N; Y1 denotes lower alkyl; n and m are equal to 0; values of radicals Y2, Y4 are given in the claim.EFFECT: improved properties of compounds.6 cl, 2 tbl, 42 ex

Heterocyclic aspartyl protease inhibitors // 2496774
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to compounds being aspartyl protease inhibitors applicable for treating cardiovascular, neurodegenerative disorders and fungal infection of formula , wherein W represents -C(=O)-; X represents -NH-; U represents -C(R6)(R7)-; R1 represents methyl, R2, R3 and R6 represent H, R4 and R7 represent optionally substituted phenyl, as well as tautomers and pharmaceutically acceptable salts thereof.EFFECT: there are presented new effective aspartyl protease inhibitors specified in rennin, cathepsin D, BACE-1, for treating cardiovascular diseases, cognitive and neurodegenerative diseases, as well as fungal infections.67 cl, 1 tbl, 4393 ex

Pharmaceutically acceptable salts of 2-{4-[(3s)-piperidin-3-yl]phenyl}-2h-indazole-7-carboxamide // 2495035
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to pharmaceutically acceptable salts of amide-substituted indazole, namely to 4-methylbenzene sulphonate (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl}piperidinium; (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl}piperidinium benzene sulphate and 4-methylbenzene sulphonate (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl]phenyl}piperidinium monohydrate, as well as to stereo isomers and tautomers thereof. Besides, the invention refers to a pharmaceutical composition for treating or preventing the states that can be relieved by poly-ADP-ribosopolymerase (PARP) inhibition, to a combination of salts and an anticancer agent, to using them and to a method of treating or preventing cancer by administering these salts to a patient in need thereof.EFFECT: there are prepared and described new salts of amide-substituted indazole which are inhibitors of the enzyme poly-ADP-ribosopolymerase (PARP) formerly known as poly-ADP-ribosyntase and poly-ADP-ribosyltransferase.12 cl, 5 ex, 1 tbl

Iminopyrimidine derivatives and use thereof as microbiocides // 2487119
FIELD: chemistry.SUBSTANCE: invention describes compounds of formula I , where R1 and R2 independently denote hydrogen, C3-C7cycloalkyl, C1-C6alkyl, C2-C6alkynyl, hydrogen or pyridine; or R1 and R2 together with a nitrogen atom which binds them form a pyrroline group; R3 denotes hydrogen, C1-C6halogenalkyl, C1-C6alkyl, halogen, cyano group, nitro group, C1-C4alkoxy group, phenyl, halogen-substituted phenyl, (R51)(R52)(R53)Si-(C2-C6alkynyl)-, where R51, R52, R53 independently denote halogen, cyano group, C1-C6alkyl, C2-C6alkenyl, C3-C8cycloalkyl, C5-C8cycloalkenyl, C2-C6alkynyl, C1-C6alkoxy group, benzyl or phenyl; R4 denotes hydrogen, halogen, phenyl, imidazolyl, amino group, C1-C6alkoxy group or C1-C6alkyl; R5 denotes C1-C12alkyl or a group A, where A denotes a 3-10-member monocyclic or condensed bicyclic ring system which can be aromatic, partially unsaturated or completely saturated, where said 3-10-member ring system can be mono- or polysubstituted with substitutes independently selected from a group comprising halogen, C1-C6alkyl, C1-C6halogenalkyl, C1-C6alkoxy group and C1-C6alkylthio group; R6 denotes hydrogen; and R7 denotes hydrogen or C1-C6alkyl and agronomically acceptable salts/metal complexes/metalloid complexes/isomers/structural isomers/stereoisomers. The invention also relates to methods of controlling infection of useful plants by phytopathogenic microorganisms by applying a compound of formula I onto the plants, a part thereof or place where said plants grow, as well as a composition for controlling infection by phytopathogenic microorganisms.EFFECT: novel compounds which are suitable for use as microbiocides are obtained and described.7 cl, 48 ex, 151 tbl

Azabiphenylaminobenzoic acid derivatives as dhodh inhibitors // 2481334
FIELD: chemistry.SUBSTANCE: invention describes novel azabiphenylaminobenzoic acid derivatives, having the chemical formula: , where R1 is selected from a group consisting of hydrogen atoms, halogen atoms, C1-4-alkyl, C3-4-cycloalkyl and -CF3, R2 is selected from a group consisting of hydrogen atoms, halogen atoms and C1-4-alkyl group, R3 is -COOR5, where R5 is selected from a group consisting of a hydrogen atom and linear or branched C1-4-alkyl groups, R4 is selected from a group consisting of a hydrogen atom and C1-4-alkyl group; R9 is selected from a group consisting of a hydrogen atom and a phenyl group, G1 is a group selected from N and CR6, where R6 is selected from a group consisting of hydrogen atoms, halogen atoms, C1-4-alkyl, C3-4-cycloalkyl, -CP3 and C6-10-aryl group, G2 is a group selected from: - a hydrogen atom, hydroxy group, halogen atom, C3-4-cycloalkyl group, C1-4-alkoxy group and -NRaRb, where Ra is C1-4-alkyl group and Rb is selected from a group consisting of C1-4-alkyl group and C1-4-alkoxy-C1-4-alkyl group, or Ra and Rb together with the nitrogen atom with which they are bonded, form a saturated 6-8-member heterocyclic ring optionally containing one oxygen atom as an additional heteroatom, -monocyclic or bicyclic 5-10-member heteroatomatic ring containing one or more nitrogen atoms which are optionally substituted with one or more halogen atoms, and a phenyl group which is optionally substituted with one or more substitutes selected from halogen atoms, C1-4-alkyl, hydroxy group, C1-4-alkoxy group, C3-4-cycloalkyl, C3-4-cycloalkoxy group, cyano group, -CF3, -OCF3, -CONR7R8, oxadiazolyl, and where R7 and R8 are independently selected from a hydrogen atom, a linear or branched C1-4-alkyl group, C3-7-cycloalkyl group, or R7 and R8 together with a nitrogen atom with which they are bonded form a group of formula: , where n equals 0-3; or G2 together with R6 form a non-aromatic C5-10-carbocyclic group or a C6-10-aryl group, and pharmaceutically acceptable and N oxides thereof. Also described are pharmaceutical compositions containing said compounds and use thereof in treatment as dehydroorotate dehydrogenase (DHODH) inhibitors.EFFECT: novel compounds which can be used as dehydroorotate dehydrogenase inhibitors are obtained and described.30 cl, 118 ex

Heteroaryl pyrrolidinyl and piperidinyl ketone derivatives // 2479575
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I or use thereof to prepare a medicine for treating depression, anxiety or both: or pharmaceutically acceptable salts thereof, where m is 0-3; n is 0-2; Ar is: optionally substituted indolyl; optionally substituted indazolyl; azaindolyl; 2,3-dihydro-indolyl; 1,3-dihydro-indol-2-one-yl; optionally substituted benzothiophenyl; benzothiazolyl; benzisothiazolyl; optionally substituted quinolinyl; 1,2,3,4-tetrahydroquinolinyl; quinolin-2-one-yl; optionally substituted naphthalenyl; optionally substituted pyridinyl; optionally substituted thiophenyl or optionally substituted phenyl; R1 is: C1-6alkyl; hetero-C1-6alkyl; halo-C1-6alkyl; halo-C2-6alkenyl; C3-7cycloalkyl; C3-7cycloalkyl-C1-6alkyl; C1-6alkyl-C3-6cycloalkyl-C1-6alkyl; C1-6alkoxy; C1-6alkylsulphonyl; phenyl; tetrahydropyranyl-C1-6alkyl; phenyl-C1-3alkyl, where the phenyl part is optionally substituted; heteroaryl-C1-3alkyl; R2 is: hydrogen or C1-6alkyl; and each Ra and Rb is independently: hydrogen; C1-6alkyl; C1-6alkoxy; halo; hydroxy or oxo; or Ra and Rb together form C1-2alkylene; under the condition that, when m is 1, n is 2, and Ar is an optionally substituted phenyl, then R1 is not methyl or ethyl, and where optionally substituted denotes 1-3 substitutes selected from alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, cyano, amino, acylamino, monoalkylamino, dialkylamino, hydroxyalkyl, alkoxyalkyl, pyrazolyl, -(CH2)q-S(O)rRf; -(CH2)q-C(=O)-NRgRh; -(CH2)q-N(Rf)-C(=O)-Ri or -(CH2)q-C(=O)-Ri; where q is 0, r is 0 or 2, each Rf, Rg and Rh is independently hydrogen or alkyl, and each Ri is independently alkyl, and where "heteroaryl" denotes a monocyclic radical having 5-6 ring atoms, including 1-2 ring heteroatoms selected from N or S, wherein the rest of the ring atoms are C atoms, "heteroalkyl" denotes an alkyl radical, including a branched C4-C7-alkyl, where one hydrogen atom is substituted by substitutes selected from a group consisting of -ORa, -NRbH, based on the assumption that the bonding of heteroalkyl radical occurs through a carbon atom, where Ra is hydrogen or C1-6alkyl, Rb is C1-6alkyl. Pharmaceutical compositions based on said compound are also disclosed.EFFECT: obtaining novel compounds which can be used in medicine to treat depression, anxiety or both.14 cl, 1 tbl, 28 ex

Dual-acting antihypertensive compounds, methods for preparing them, based pharmaceutical compositions and intermediate compounds // 2476427
FIELD: medicine, pharmaceutics.SUBSTANCE: present invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts wherein r represents 1; Ar is specified in and , R1 is specified in -COOR1a, -NHSO2R1b, -SO2NHR1d, -SO2OH, -O-CH(R1e)-COOH and tetrazol-5-yl, R1a represents H, -C1-6alkyl, -C1-3alkylenaryl, -C1-3alkyleneheteroaryl, - C3-7cycloalkyl, -CH(C1-4alkyl)OC(O)R1aa, or R1aa represents -O-C1-6alkyl or -O-C3-7cycloalkyl; R1b represents R1c; R1d represents -C1-6alkyl or -C0-4alkylenaryl; R1d represents -C(O)R1c or -C(O)NHR1c; R1e represents -C1-4alkyl; Y represents -C(R3)-, Z represents -N-, Q represents -C(R2)-, and W represents a bond; Y represents -N-, Z represents -C(R3)-, Q represents -C(R2)-, and W represents a bond; Y represents -C(R3)-, Z represents -N-, Q represents -N-, and W represents a bond; or Y represents -C(R3)-, Z represents -CH-, Q represents -C(R2)-, and W represents -C(O)-; R2 is specified in H, halogen, -C1-6alkyl, -C3-6dicloalkyl, and -C0-5alkylene-OR2b; wherein R2b is specified in H and -C1-6alkyl; R3 is specified in -C1-10alkyl and -C0-5alkylene-O-C0-5alkylene-R3b; and R3b represents -C1-6alkyl; X represents -C1-12alkylene-, where at least one group -CH2- in alkylene is substituted by the group -NR4a-C(O)- or -C(O)-NR4a-, wherein R4a is specified in H, -OH, and -C1-4aalkyl; R5 is specified in -C0-3 alkylene-SR5a, -C0-3alkylene-C(O)NR5bR5c, -C0-3alkylene-NR5b-C(O)R5d, -NH-C0-1alkylene-P(O)(OR5e)2, -C0-2alkylene-CHR5g-COOH and -C0-3alkylene-C(O)NR5h-CHR5i-COOH; R5a represents H or -C(O)-R5aa; R5aa represents -C1-6alkyl, -C0-6alkylene-C3-7cycoalkyl, -C0-6alkylenaryl, or -C0-6alkylenemorpholine; R5b represents -OH, -OC(O)R5ba, -CH2COOH or -OC(S)NR5bbR5bc; R5ba represents -C1-6alkyl, -OCH2-aryl or -CH2O-aryl; R5bb and R5bc independently represents -C1-4alkyl; R5c represents H; R5d represents H; R5e represents H; R5g represents H or -CH2-O-(CH2)2-O-CH3; R5h represents H; R5i represents -C0-3alkylenaryl; R6 is specified in -C1-6alkyl, -C0-3alkylenaryl, -C0-3alkyleneheteroaryl and -C0-3alkylene-C3-7cycloalkyl; and R7 represents H or together with R6 to form -C3-7cycloalkyl; where each ring in Ar and each aryl and heteroaryl in R1-3 and R5-6 are optionally substituted by 1-3 substitutes optionally specified in -C1-6alkyl, -CN, halogen, -O-C1-6alkyl, -phenyl, -NO2, wherein each alkyl is optionally substituted by 1-5 fluorine atoms; each carbon atom in X is optionally substituted by one or more groups R4b, and one group -CH2- in X may be substituted by -C4-8cycloalkylene- and -CH=CR4d-; where R4b is specified in -C0-5alkylene-COOR4c and benzene, where R4c represents H; and R4d represents -CH2-thiophen; each alkyl and each aryl in R1-3, R4a-4d and R5-6 are optionally substituted by 1-7 fluorine atoms; where aryl represents monovalent aromatic hydrocarbon having one ring or condensed rings, and contains 6-10 carbon atoms in the ring; and heteroaryl represents a monovalent aromatic group having one ring or two condensed rings, and having 5-10 atoms in large in the ring with one atom of the ring represents a heteroatom specified in nitrogen, oxygen and sulphur. Besides, the invention refers to a pharmaceutical composition based on the compound of formula , to a method for preparing the compound of formula (I), to intermediate compounds used in synthesis of the compound of formula (I), to the use of the compounds of formula (I).EFFECT: there are prepared new compounds possessing activity of a type 1 angiotensin II (AT1) receptor antagonist and activity of neprilysin inhibition.38 cl, 36 ex

Pyridinone pyridazinone derivatives as inhibitors of poly(adp-ribose) polymerase (parp) // 2472782
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula (IX) wherein radicals and symbols have values given in the claim, and pharmaceutically acceptable salts or tautomers thereof. Said compounds are inhibitors of poly(ADP-ribose)polymerase (PARP) and can be used to treat cancer, inflammatory diseases, reperfusion injuries, ischaemic conditions, stroke, renal failure, cardiovascular diseases, vascular diseases other than cardiovascular diseases, diabetes mellitus, neurodegenerative diseases, retroviral infections, retinal damage, skin senescence and UV-induced skin damage, and as chemo- or radiosensitisers for cancer treatment. The invention also relates to a pharmaceutical composition containing said compounds, use of said compounds and a method of treating said diseases.EFFECT: high efficiency of using the compounds.10 cl, 18 ex

Novel 707 compounds and use thereof // 2472781
FIELD: chemistry.SUBSTANCE: invention relates to novel isoquinolinone derivatives of formula (I) , wherein R1 is selected from H, (C1-C6)alkyl, (C2-C6)alkenyl, (CH2)a-X-Ar and (CR101R102)a-X-Ar, where said (C1-C6)alkyl is optionally substituted with 1, 2 or 3 groups independently selected from -(C1-C6)alkoxy, -halogen, -OH, -heterocycloalkyl, (C3-C7)cycloalkyl and -NR8R9; R2 is selected from H and (C1-C6)alkyl; R is selected from H, (C1-C6)alkyl and (CH2)d-Y; provided that when R3 is (CH2)d-Y, R2 is selected from H; R4 and R5 are independently selected from H, (C1-C6)alkyl and halogen; R is (C3-C7)cycloalkyl; R7 is H; Ar is phenyl or heteroaryl, optionally substituted with 1, 2 or 3 groups independently selected from -(C1-C6)alkyl, -(CH2)e-O-(C1-C6)alkyl, -(CH2)e-S(O)f(C1-C6)alkyl, -(CH2)e-N(R10)-(C1-C6)alkyl, -(CH2)e-Z-(C1-C6)alkyl, -halogen, heterocycloalkyl, -C(O)NR8R9, -NR8R9 and -C(O)OH, where (C1-C6)alkyl in each case is independently optionally substituted with 1, 2 or 3 groups, independently selected from -NRI2R13; X is selected from a single bond; Y is NR16R17, where R16 and R17 together with a nitrogen atom with which they are bonded form a 5-7-member ring, optionally containing an additional heteroatom NR27, where said ring is optionally substituted on the carbon atom with 1 or 2 substitutes independently selected from -(C1-C6)alkyl, where said -(C1-C6)alkyl is optionally substituted with -OH; and where R27 is selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with -OH; Z is selected from C(O)N(R18); R8 and R9 are independently selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with 1, 2 or 3 groups, independently selected from NR19R20; or R8 and R9 together with the nitrogen atom with which they are bonded form a 5-6-member ring, optionally containing an additional heteroatom, selected from NR21; R12 and R13 are independently selected from H and (C1-C6)alkyl, where said (C1-C6)alkyl is optionally substituted with -(C1-C6)alkoxy, -OH; or R12 and R13 together with the nitrogen atom with which they are bonded form a 5-6-member ring optionally containing an additional heteroatom selected from NR24; R10, R18, R19, R20, R21, R22, R23 and R24 are independently selected from H and (C1-C6)alkyl; a is selected from 1, 2, 3, 4, 5 and 6; d equals 0 or 1; e equals 0; f is independently selected from 1 and 2; where the heterocycloalkyl is a 5-6-member non-aromatic cyclic ring bonded at a C atom, having 1-2 NR28 atoms; optionally having one double bond; the heteroaryl is a 6-member aromatic ring containing 1 N atom; R is selected from H, (C1-C6)alkyl and -C(O)O-(C1-C6)alkyl; R101 is (C1-C6)alkyl; R102 is H; or pharmaceutically acceptable salts thereof or N-oxides. The invention also relates to methods of producing said compounds and use thereof as a p38 kinase inhibitor.EFFECT: improved method.13 cl, 4 dwg, 1 tbl, 128 ex

Compounds binding btr domain of iap proteins // 2472780
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula (I) or (II) including enantiomer or diastereomer thereof, where values of R1, R2, R3, R100, R200, R300, A, A1, BG, Q and Q1 are given in claim 1.EFFECT: compounds can be used to treat proliferative disorders, for example, cancer.42 cl, 36 dwg, 7 tbl

New compounds // 2456273
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to compounds of formula: wherein B is specified in a group consisting of pyridine, pyridazine, pyrimidine and oxazole which can be optionally substituted by halogen, C1-7-alkyl or a C1-7-alkoxy group; L1 is specified in a group consisting of -NH-, -C(O)NH- and -NHC(O)-, A means C3-C12-cycloalkyl, C6-C12-aryl, a 4-7-member monocyclic heterocyclic group consisting of 1-3 heteroatoms optionally specified in O N and S, or a bicyclic heterocyclyl specified in a group consisting of benzimidazolyl, benzoxazolyl, benzothiazolyl, wherein cycloalkyl, aryl, mono- or bicyclic heterocyclyl can be optionally substituted by one or more substitutes optionally specified in a group consisting of a cyano group, halogen, an oxo group, C1-7-alkyl, C1-7-halogenalkyl, a C1-7-alkoxy group, C1-7-halogenalkoxy group, an amino group, a di-C1-7-alkylamino group, a C1-7-alkylthio group and C3-8-cycloalkyl, 1-2- means a bivalent residue specified in a group consisting of: - a bivalent alkyl group consisting of 1 to 4 carbon atoms, a bivalent alkenyl group consisting of 2 to 3 carbon atoms, - -C(O)-, - -C(O)-[R4]c-R5- wherein c is equal to 0, and R5 is specified in a group consisting of a bivalent C1-C4-alkyl group optionally substituted by another C1-4-alkyl, a C4-C8-cycloalkyl group, a phenyl group and a 5- or 6-member heterocyclyl group consisting of N heteroatoms, - -C(O)-NH-, - -(CH2)1-3-C(O)-NH-(CH2)1-3-, - -C(O)-NH-R4- wherein R4 is specified in a group consisting of a bivalent C1-C7-alkyl group optionally substituted by another C1-4-alkyl, a cyclohexyl group and a cyclopentyl group, and E is specified in a group consisting of: - COOH, - a ester group of carboxylic acid, or to its pharmaceutically acceptable salts. What is also described is a pharmaceutical composition exhibiting DGAT1 modulatory activity, on the basis of the presented compounds, and also a method of treating pathological conditions or disorders associated with DGAT1 activity.EFFECT: there are prepared and described new compounds applicable for treating or preventing the pathological conditions or disorders associated with DGAT1 activity.22 cl, 8 ex

Poly(adp-riboso)polymerase inhibitors // 2455286
FIELD: medicine, pharmaceutics.SUBSTANCE: invention describes poly(ADP-riboso)polymerase inhibitors of formula (Ik) its pharmaceutically acceptable salt wherein R101, R104 and R105 represent H; R102 represents R11 wherein R11 is specified from pyrrolidinyl, oxazolyl, imidazolidinyl, isothiazolidinyl, piperidinyl, piperazinyl and azepanyl with R102 being substituted by one or two (O) substitutes; R103 represents fluorine, besides, a pharmaceutical composition on the basis of said compounds showing poly(ADP-riboso)polymerase (PARP) inhibitory activity, a method of treating cancer and a method of reducing tumour volume in a mammal.EFFECT: there are produced and described new compounds which show poly(ADP-riboso)polymerase (PARP) inhibitory activity.9 cl, 491 ex, 2 tbl

Novel pyridone derivatives, having mch antagonist activity, and medicinal agent containing said compounds // 2453543
FIELD: chemistry.SUBSTANCE: invention relates to compounds of general formula (I), , where groups and radicals R1, R2 independently denote H, C1-8-alkyl or C3-7-cycloalkyl, where the alkyl or cycloalkyl group can be mono- or poly-substituted with identical or different groups R11; or R2 denotes a -CH2- or -CH2-CH2- bridge which is bonded with a group Y, and R1 is as defined above, or denotes a group selected from C1-4-alkyl-CO-, C1-4-alkyl-O-CO-, (C1-4-alkyl)NH-CO- or (C1-4-alkyl)2N-CO-, where the alkyl groups can be mono- or polyfluorinated; or R1 and R2 form an alkylene bridge such that R1R2N- denotes a group selected from: azetidine, pyrrolidine, piperdine, azepan, 2,5-dihydro-1H-pyrrole, 1,2,3,6-tetrahydropyridine, 2,3,4,7-tetrahydro-1H-azepine, 2,3,6,7-tetrahydro-1H-azepine, piperazine, in which the free amino group is substituted with R13, piperidin-4-one, morpholine, thiomorpholine, 4-C1-4-alkoxy iminopiperidin-1-yl and 4-hydroxy iminopiperidin-1-yl. Wherein, when R1 and R2 form an alkylene bridge, one or more H atoms in the alkylene bridge can be substituted with identical or different groups R14, and X denotes a C1-3-alkylene bridge which can contain one, two or three identical or different C1-3-alkyl substitutes; and Y denotes a group of subformula selected from: and , where the group can be mono-substituted with a substitute R20; Z denotes -CH2-CH2- or -C(=O)-CH2-; U, V both denote CH, one of groups U, V denotes N, and the other of U, V denotes CH, where CH can be substituted with L; and L independently denotes halogen, cyano or C1-3-alkyl; and k equals 0, 1 or 2; W is selected from a group consisting of -CH2-O- and -O-CH2-; B is selected from a group consisting of phenyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, thiophenyl and thiazolyl; each of which can be mono- or poly-substituted with identical or different substitutes R20; radicals R11, R13, R14, R20 assume values given in claim 1. The invention also relates to a pharmaceutical composition containing at least one compound of formula I and having action on MCH receptor.EFFECT: disclosed pharmaceutical compositions are useful in treating metabolic disorders or eating disorders, especially obesity, bulimia, anorexia, hyperphagia and diabetes.

2,3-substituted pyrazine sulphonamides as crth2 inhibitors // 2453540
FIELD: chemistry.SUBSTANCE: invention relates to 2,3-substituted pyrazine sulphonamides of formula (I), use thereof in treating allergic diseases, inflammatory dermatosis, immonological disorders and neurodegenerative disorders, as well as pharmaceutical compositions, having CRTH2 receptor inhibiting action and inhibiting chemoattractant receptor, homologous to the molecule expressed on T-helpers 2. in general formula . A is selected from a group consisting of , n denotes an integer independently selected from 0, 1, 2, 3 or 4; m equals 1 or 2; B is selected from a group consisting of phenyl or piperazinyl; R1 denotes hydrogen; R2 denotes phenyl, where R2 is optionally substituted with one or more substitutes selected from a group consisting of halogen, cyano, (C1-C6)alkyl; R3 is selected from a group consisting of (C1-C6)alkyl, aryl, heteroaryl, (C1-C6)alkylaryl, (C1-C6)alkylheteroaryl, (C3-C8)cycloalkyl and (C3-C8)heterocycloalkyl, where each of said (C1-C6)alkyl, aryl, heteroaryl, (C1-C6)alkylaryl, (C1-C6)alkylheteroaryl, (C3-C8)cycloalkyl and (C3-C8)heterocycloalkyl is optionally substituted with one or more substitutes selected from a group consisting of halogen, cyano, (C1-C6)alkyl, (C1-C6)alkoxy, heteroaryl, aryl, thioalkoxy and thioalkyl, or where said aryl, heteroaryl, (C1-C6)alkylaryl, (C1-C6)alkylheteroaryl, (C3-C8)cycloalkyl or (C3-C8)heterocycloalkyl can be condensed with one or more aryl, heteroaryl, (C3-C8)cycloalkyl or (C3-C8)heterocycloalkyl groups and can be substituted with one or more substitutes selected from a group consisting of (C1-C6)alkyl, alkoxy, aryl, heteroaryl, carboxyl, cyano, halogen, hydroxy, amino, aminocarbonyl, nitro, sulphoxy, sulphonyl, sulphonamide and trihaloalkyl; R7 is selected from a group consisting of hydrogen, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, aryl, heteroaryl, (C3-C8)cycloalkyl, (C3-C8)heterocycloalkyl, carboxyl, cyano, amino and hydroxy; aryl is selected from phenyl or naphthyl; and heteroaryl is selected from pyridyl, indolyl, 3H-indolyl, benzimidazolyl, quinolizinyl.EFFECT: high efficiency of using the compounds.4 cl, 10 dwg, 46 ex

Pyridine and pyrimidine derivatives as mglur2 antagonists // 2451673
FIELD: medicine, pharmaceutics.SUBSTANCE: this invention relates to new compounds with formula (I) possessing the properties of mGLuR2 antagonists, to their obtainment methods, their application for production of medicines for prevention and treatment of disorders wherein mGLuR2 plays the activation role (in particular - central nervous system disorders). In formula (I) either any of X and Y represents N while the other represents CH or each of X and Y represents N; A represents aryl representing phenyl or 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur, the heteroaryl selected from among amidazolyl, [1,2,4] oxadiazolyl, pyrrolyl, 1H-pyrazolyl, pyridinyl, [1,2,4] triazolyl, tiazolyl and pyrimidinyl, each of them substitutable by C1-6-alkyl; B represents H, cyano or represents a possibly substituted aryl selected from among phenyl or possibly substituted by 5- or 6-membered heteroaryl containing in the cycle 1-3 atoms selected from among nitrogen, oxygen or sulphur where the substitutes are selected from the group consisting of nitro, C1-6-alkyl, possibly substituted hydroxy, NRaRb where Ra and Rb independently represent H, C1-6-alkyl etc. R1 represents H, a halogen atom, C1-6-alkyl, possibly substituted hydroxy, C1-6-alcoxy, C1-6-halogenoalkyl, C3-6-cycloalkyl represents H cyano, a halogen atom, C1-6-halogenoalkyl, C1-6-alcoxy, C1-6-halogenoalcoxi-, C1-6-alkyl or C3-6-cycloalkyl R3 represents a halogen atom, H, C1-6-alcoxy, C1-6-halogenoalkyl, C1-6-alkyl, C3-6-cycloalkyl, C1-6-halogenoalcoxy R4 reprsents H or halogeno.EFFECT: creation of new compounds of formula (I) possessing mGLuR2 antagonist properties.104 cl, 465 ex

Cyclopropylamide derivatives as n3-histamine receptor modulators // 2449989
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new cyclopropylamine derivatives of formula: or its pharmaceutically acceptable salt, wherein: one of R1 and R2 means a group of formula -L2-R6a-L3-R6b; the other of R1 and R2 means H, C1-10alkyl, C1-10alkoxy, halogen, CN; each R3, R3a R3b independently means H, C1-6alkyl, trifluoromethyl, C1-10alkoxy, CN; R4 and R5 taken together with a nitrogen atom whereto each attached form a non-aromatic cycle of formula: R7, R8, R9 and R10 each H, C1-10alkyl; R6a means cyanophenyl, phenyl, pyrazolyl, pyridazinyl, pyridinyl, pyrimidinyl, [1,2,3]triazolyl, [1,2,4]triazolyl, azepanyl, azetidinyl, azetidin-2-onyl, pyridazin-3(2H)-onyl, pyridin-2(1H)-onyl, pyrimidin-2(1H)-onyl, pyrrolidin-2-onyl, benzothiazolyl wherein the pyridinyl and pyrimidinyl groups optionally contain 1-3 substitutes specified in a group consisting of C1-10alkyl and C1-10alkoxy; R6b means H; L means - [C(R16)(R17)]k; L2 means a bond, C2-10alkylene, -O-, -C(=O)-, -NH-, -N(R16)C(=O), -C(=O)N(R16) and -N(C1-6alkyl)-;L3 means a bond; R15 means H, C1-6alkyl, C1-6alkoxycarbonyl, amido and formyl R16 , R17 in each specific case means H, C1-6alkyl; Rx and Ry in each specific case independently mean H, C1-6alkyl, C1-6alkoxy, C1-6alkylamino, fluorine, diC1-6alkylamino; k is equal to 1, 2 or 3; m is equal to 2.EFFECT: compounds show H3 receptor inhibitory activity that makes them applicable in a pharmaceutical composition.10 cl, 7 dwg, 44 ex

Substituted isoindoles as bace inhibitors and use thereof // 2446158
FIELD: medicine, pharmaceutics.SUBSTANCE: invention refers to new compounds of formula , wherein: R1 means phenyl, 6-member heteroaryl containing one or two atoms N as heteroatoms and wherein said phenyl, 6-member heteroaryl is optionally substituted by one R7; R2 means phenyl, 6-member heteroaryl containing one or two atoms N as heteroatoms and wherein each of said phenyl or 6-member heteroaryl is optionally substituted by one R7; R3 means halogen R7 independently means halogen, OR8, phenyl, 6-member heteroaryl containing one or two atoms N as heteroatoms wherein any phenyl or heteroaryl can be optionally substituted by one R14; R14 means halogen, OR8; R8 independently means C1-6alkyl; m is equal to 1; in the form of a free base or its pharmaceutically acceptable salt, and to their pharmaceutically acceptable salt.EFFECT: compounds possess BACE inhibitory activity.8 cl, 6 tbl, 136 ex

Compounds and compositions as gpr119 activity modulators // 2443699
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula I: or pharmaceutically acceptable salts thereof, in which Q is a divalent or trivalent radical selected from C6-10aryl and heteroaryl; where said aryl or heteroaryl in Q is optionally substituted up to 3 times with radicals independently selected from halogen, C1-6 alkyl, C1-6 alkyl substituted with halogen, C1-6 alkoxy group, C1-6 alkoxy group substituted with halogen, -C(O)R20 and -C(O)OR20; where R20 is selected from hydrogen and C1-6 alkyl; and where optionally, the carbon atom neighbouring W2 can be bonded through CR31 or O with a carbon atom of Q to form a 5-member ring condensed with A and Q rings; where R31 is selected from hydrogen and C1-6 alkyl; W1 and W2 are independently selected from CR21 and N; where R21 is selected from hydrogen and -C(O)OR25; where R25 denotes hydrogen; ring A can contain up to 2 carbon ring atoms substituted with a group selected from -C(O)-, -C(S)- and -C(=NOR30)- and can be partially unsaturated and contain up to 2 double bonds; where R30 denotes hydrogen ; L is selected from C1-6alkylene, C2-6alkenylene, -OC(O)(CH2)n-, -NR26(CH2)n- and -O(CH2)n-; where R26 is selected from hydrogen and C1-6 alkyl; where n is selected from 0, 1, 2, 3 and 4; q is selected from 0 and 1; t1, t2, t3 and t4 are each independently selected from 0, 1 and 2; R1 is selected from -X1S(O)0-2X2R6a, -X1S(O)0-2X2OR6a, -X1S(O)0-2X2C(O)R6a, -X1S(O)0-2X2C(O)OR6a, -X1S(O)0-2X2OC(O)R6a and -X1S(O)0-2NR6aR6b; where X1 is selected from a bond, O, NR7a and C1-4alkylene; where R7a is selected from hydrogen and C1-6alkyl; X2 is selected from a bond and C1-6alkylene; R6a is selected from hydrogen, cyanogroup, halogen, C1-6alkyl, C2-6alkenyl, C6-10aryl, heteroaryl, heterocycloalkyl and C3-8cycloalkyl; where said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in R6a is optionally substituted with 1-3 radicals independently selected from hydroxy group, halogen, C1-6alkyl, C1-6alkyl substituted with a cyano group, C1-6alkoxy group and C6-10aryl-C1-4alkoxy group; and R6b is selected from hydrogen and C1-6alkyl; R3 is selected from hydrogen, halogen, hydroxy group, C1-6alkyl, C1-6alkyl substituted with halogen, C1-6alkyl substituted with a hydroxy group, C1-6alkoxy group, C1-6alkoxy group substituted with halogen, -C(O)R23 and -C(O)OR23; where R23 is selected from hydrogen and C1-6alkyl; R4 is selected from R8 and -C(O)OR8; where R8 is selected from C1-6alkyl, heteroaryl, C3-8cycloalkyl and heterocycloalkyl; where said heteroaryl, cycloalkyl or heterocycloalkyl in R8 is optionally substituted with 1-3 radicals independently selected from halogen, C1-6alkyl, C3-8cycloalkyl and C1-6alkyl substituted with halogen; R5 is selected from hydrogen, C1-6alkyl substituted with a hydroxy group, and a C1-6alkoxy group; heteroaryl denotes a monocyclic or condensed bicyclic aromatic ring complex containing 5-9 carbon atoms in the ring, where one or more ring members are heteroatoms selected from nitrogen, oxygen and sulphur, and heterocycloalkyl denotes a saturated monocyclic 4-6-member ring in which one or more said carbon atoms in the ring are substituted with a group selected from -O-, -S- and -NR-, where R denotes a bond, hydrogen or C1-6alkyl. The invention also relates to pharmaceutical compositions containing said compounds, and methods of using said compounds to treat or prevent diseases or disorders associated with GPR119 activity, such as obesity, type 1 diabetes, type 2 sugar diabetes, hyperlipidemia, type 1 autopathic diabetes, latent autoimmune diabetes in adults, type 2 early diabetes, child atypical diabetes, adult diabetes in children, malnutrition-associated diabetes and diabetes in pregnant women.EFFECT: improved properties of compounds.27 cl
 
2551072.
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