Linked by a chain containing hetero atoms as chain links (C07D401/12)

C   Chemistry; metallurgy(318327)
C07   Organic chemistry(61593)
C07D401/12                     Linked by a chain containing hetero atoms as chain links(846)
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
ultifunctional quinoline derivatives as antineurodegenerative agents // 2642466
FIELD: chemistry.SUBSTANCE: invention relates to a hydroxy-derived quinoline of the formula (I) or to a pharmaceutically acceptable salt thereof, (I) wherein R1 is hydrogen, (C1-C3)alkyl, (C1)alkylene(C3)cycloalkyl, (C1)haloalkyl or (C1)alkylene(C6)aryl; R2 is hydrogen or halogen; R3 is hydrogen, halogen, (C1)alkyl or (C1)alkoxy; R4 is hydrogen, halogen, (C1)alkyl, (C1)alkoxy or (C1)haloalkyl; R5 and R6 are hydrogen; and R7 is (C9-C15)alkanol, (C1)alkylenepiperazinyl(C1-C2)alkanol, (C1-C8)alkylenepiperazinyl (C1-C2)alkyl, (C10-C13)alkylene OCOCH3, (C1)alkylene(C1)alkylamino(C3)alkynyl, (C1)alkyleneamino(C8)alkanol or (C1)alkyleneamino(C6)alkanol(C1)alkylene(8-methoxyquinolin-2-yl); or (II), where R1, R2, R3, R4 and R6 each is as described in (I) above; R5 is (C11-C12)alkanol, and R7 is hydrogen. The invention also relates to a pharmaceutical composition based on the formula (I) compounds, a method for treatment of Alzheimer's disease, traumatic brain injury and/or damage to the spinal cord and a method for improvement of the ability of learning and/or memory in a patient suffering from Alzheimer's disease, based on the formula (I) compound.EFFECT: new hydroxy derivatives of quinoline have been obtained that have useful biological properties.13 cl, 13 dwg, 9 ex
Amide derivatives as grp119 agonists // 2642429
FIELD: pharmacology.SUBSTANCE: invention relates to an amide derivative of the following formula 1, its stereoisomers or its pharmaceutically acceptable salts of formula 1, wherein X1, X2, X3, X4, X5, X6, X7 and X8 each independently is C or N; R1 is -F or -C1-3-perfluorinated alkyl; R2 and R3 each is independently selected from the group consisting of halogen, -C1-5-alkyl and C3-6-cycloalkyl, wherein -C1-5-alkyl and C3-6cycloalkyl independently of one another may be unsubstituted or substituted by halogen, -CN, -OC1-5-alkyl or-C1-5-alkyl, or R2 and R3 together with the carbon atom to which they are attached, can form C3-6-cycloalkyl, where C3-6cycloalkyl may be unsubstituted or substituted by halogen, -OC1-5-alkyl or -C1-5-alkyl; R4 and R5 each independently is H, halogen or -C1-5-alkyl; R6 and R7 each independently is H, halogen, -C1-5-alkyl or -CN; R8 means methyl; R9 means H, halogen or OH; and m is 1 or 2. The invention also relates to individual compounds and to a pharmaceutical composition.EFFECT: new compounds of formula 1 are obtained that have the properties of GPR119 agonists, which can be used in diabetes mellitus treatment.7 cl, 15 tbl
5-(pyridine-2-ylamino)-pyrasin-2-carbonitrile compounds and their therapeutic application // 2641693
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula , as well as to pharmaceutical compositions based thereon for use in the treatment of a disease or condition mediated by SNK1.EFFECT: new compounds are obtained that inhibit the kinase function of kinase 1 of the control point.37 cl, 2 dwg
New anti-invasive compounds // 2641650
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula or pharmaceutically acceptable salts thereof, which can be used to prevent, and/or inhibit, and/or treat cancer. In formula (I) A and A' independently represent phenyl or pyridylene group; R2 represents a hydrogen or alkyl group (C1-C4); R3 represents a 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 2-pyrimidinyl group, 4-pyrimidinyl group or 5-pyrimidinyl group; R4 represents a carbonyl group or sulfonyl group; R5 is a -NH-(CH2)(a)-NR6R7 group or a 4-methylpiperazinyl group and a is an integer from 1 to 4, R6 and R7 independently represent a nalkyl group (C1-C4) or R6 R7 together with nitrogen atom they are bounded to form a heterocyclic group selected from 4-methylpiperazinyl group, morpholine group, pyrrolidinyl group and piperidine group. The invention also relates to a method for preparation of compounds of formula (I) and a pharmaceutical composition containing them.EFFECT: improved compounds properties.16 cl, 6 tbl, 17 ex
Partly saturated nitrogen-containing heterocyclic compound // 2641291
FIELD: chemistry.SUBSTANCE: invention relates to a compound of the formula (I'), (wherein W represents the formula -CR11R12CR13R14-; R11 represents a hydrogen atom, a fluorine atom, C1-4 alkyl or phenyl; R12 represents a hydrogen atom, a fluorine atom or C1-4 alkyl; provided that R11 and R12, together with the adjacent carbon atom, optionally form C3-8 cycloalkane or tetrahydropyran; R13 represents a hydrogen atom, a carbamoyl, C1-4 alkyl (C1-4 alkyl is optionally substituted by one group selected from the group consisting of hydroxy, C1-3 alkoxy and di-C1-3 alkylamino), halo-C1-4 alkyl, phenyl, pyridyl, benzyl or phenethyl; R14 represents a hydrogen atom, C1-4 alkyl or halogen-C1-4 alkyl; Y represents a single bond or C1-6 alkanediyl (C1-6 alkanediyl is optionally substituted by one hydroxy group and one of the carbon atoms in C1-6 alkanediyl is optionally substituted by cycloalkpropane-1,1-diyl); R2 represents a hydrogen atom, C1-6 alkyl, C3-8 cycloalkyl {C3-8 cycloalkyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl (C1-6 alkyl is optionally substituted by one phenyl group), phenyl (phenyl is optionally substituted by one halogen atom), C1-6 alkoxy [C1-6 alkoxy is optionally substituted by one group selected from the group consisting of C3-8 cycloalkyl, phenyl (phenyl is optionally substituted by one group selected from the group consisting of a halogen atom and C1-6 alkyl) and pyridyl (pyridyl is optionally substituted by one halogen atom)], C3-8 cycloalkoxy, phenoxy (phenoxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl, C3-8 cycloalkyl and halogen-C1-6 alkyl) and pyridyloxy (pyridyloxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl, C3-8 cycloalkyl and halogen-C1-6 alkyl)}, phenyl (phenyl is optionally substituted by one to three groups that are the same or different and which are selected from the group of α3 substituents), naphthyl, indanyl, tetrahydronaphthyl, pyrazolyl [pyrazolyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl and phenyl (phenyl optionally substituted by one C1-6 alkyl)], imidazolyl [imidazolyl is optionally substituted by one or two groups that are the same or different and are selected from the group consisting of C1-6 alkyl and phenyl], isoxazolyl [isoxazolyl is optionally substituted by one phenyl group (phenyl is optionally substituted by one halogen atom)], oxazolyl [oxazolyl is optionally substituted by one or two groups that are the same or different and which are selected from the group consisting of C1-6 alkyl and phenyl], thiazolyl [thiazolyl is optionally substituted by one or two groups that are the same or different and which are selected from the group consisting of C1-6 alkyl, phenyl and morpholino], pyridyl (pyridyl is optionally substituted by one or two groups that are are the same or different and are selected from the group of α5 substituents), pyridazinyl [pyridazinyl is optionally substituted by one C1-6 alkoxy (C1-6 alkoxy is optionally substituted by one C3-8 cycloalkyl group)], pyrimidinyl [pyrimidinyl is optionally substituted by one group selected from the group consisting of halogen-C1-6 alkyl, C3-8 cycloalkyl, phenyl and phenoxy (phenoxy is optionally substituted by one C1-6 alkyl)], pyrazinyl [pyrazinyl is optionally substituted by one group selected from the group consisting of C1-6 alkoxy (C1-6 alkoxy is optionally substituted by one C3-8 cycloalkyl), and phenoxy (phenoxy is optionally substituted by one group selected from the group consisting of a halogen atom, C1-6 alkyl and C3-8 cycloalkyl)], benzothiophenyl, quinolyl, methylenedioxyphenyl (methylenedioxyphenyl is optionally substituted by one or two fluorine atoms), azetidinyl (azetidinyl is optionally substituted with one pyrimidinyl group), piperidinyl (piperidinyl is optionally substituted by one group selected from the group consisting of pyrimidinyl, phenyl-C1-3 alkyl, C3-8 cycloalkyl-C1-3 alkylcarbonyl and phenyl-C1-3 alkoxycarbonyl) or the following formula (I") -CONR5CH2-R6 (I") [wherein in formula (I") R5 represents a hydrogen atom or C1-3 alkyl and R 6 is phenyl (phenyl is optionally substituted by one group selected from the group consisting of a halogen atom, halogen-C1-6 alkyl and phenyl)], Y4 represents C1-4 alkanediyl; R3 represents a hydrogen atom or methyl; R4 represents -COOH or -CONHOH).EFFECT: compound has a superior PHD2 inhibitory effect.16 cl, 28 tbl, 11 ex
Heterocyclic compounds, effective for kinase inhibition // 2640862
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula (I)or a pharmaceutically acceptable salt thereof, wherein Q is O; W is phenyl; X is absent; Y is NH; Z1 and Z2 are N; Z3 is NR5, where R5 is hydrogen; R1 is pyridine or pyrimidine; optionally substituted with C1-C6alkyl, C1-C6alkoxy, -NR10R11 or -SOmR12, where R10 and R11 are hydrogen, R12 is C1-C6alkyl; and m is 0; R3 is C1-C6alkyl; R2 is C1-C6alkyl when p is 1; or one R2 is C1-C6alkyl and one R2 is halogen when p is 2; or one R2 and R3 combined with formation of a five- to seven-membered carbocycle; R4 is hydrogen; p=1 or 2; and n is 1.EFFECT: heterocyclic compounds designed for cancer treatment.12 cl, 1 tbl, 8 ex

Salt of pyrrolidin-3-yl-acetic acid derivative and its crystals // 2640047
FIELD: chemistry.SUBSTANCE: invention relates to salts of organic carboxylic acids and 2-[(3S,4R)-1-{[2-chloro-6-(trifluoromethyl)phenyl]methyl}-3-{[1-(cyclohex-1-en-1-ylmethyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetic acid and their crystals.EFFECT: improved properties.15 cl, 6 dwg, 3 tbl, 7 ex
Oxothioimidazoline derivatives, methods for their production and application in medicine as androgen receptor inhibitors // 2639145
FIELD: pharmacology.SUBSTANCE: invention relates to an oxothioimidazoline derivative of the formula or to its mesomer, racemate, enantiomer, diastereomer, or a mixture thereof, wherein A is -CR' or N; R' is hydrogen or halogen; Z1 and Z2 each independently represents methyl; R1 and R2 each is independently selected from the group consisting of S or O; R3 is selected from the group consisting of C1-C3-alkyl, heterocyclyl selected from tetrahydrofuran, tetrahydropyran, piperidine, dioxo-tetrahydrothiopyran, azetidine, pyrrolidine, oxetane; C6-aryl and -S(O)mR6; when R3 is selected from heterocyclyl selected from tetrahydrofuran, tetrahydropyran, piperidine, dioxo-tetrahydrothiopyran, azetidine, pyrrolidine, oxetane; or C6-aryl, each of the heterocyclyl and aryl is optionally substituted by one or more groups selected from the group consisting of C1-alkyl, -OR6, -C(O)NR7R8, -S (O)mR6 and -C(O)R6; when R3 is C1-C3alkyl, alkyl is substituted by one or more groups selected from the group consisting of halogen, cyano, amino, C3-cycloalkyl, tetrahydrofuran, -OR6, -C(O)NR7R8, -S(O)mR6 and -C(O)OR6, wherein the cycloalkyl is optionally substituted by one group selected from cyano, amino, -OR6, -C(O)NR7R8 and -C(O)OR6; R4 and R5 are each independently selected from the group consisting of cyano, C1-alkyl, halogen and -CF3; R6 is hydrogen, C1-alkyl or -CF3; R7 and R8 are each independently selected from the group consisting of hydrogen and C1-alkyl, and m is 2. The invention also relates to intermediates, a process for preparation of a compound of formula (I), a pharmaceutical composition based on the compound of formula (I) and its application.EFFECT: new oxothiohydantoin derivatives, useful for treatment of androgen receptor mediated diseases.18 cl, 51 ex
Derivatives of 1-phenyl-2-pyridinyl-alkyl alcohols as phosphodiesterase inhibitors // 2637945
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the general formula (I) , where R1 and R2 are different or identical and are independently selected from the group consisting of: - H; -(C1-C6)haloalkyl; -(C1-C6)alkyl optionally substituted by one or more substituents selected from (C3-C7)cycloalkyl; and -(C3-C7)cycloalkyl; A is a monocyclic heteroaryl ring system selected from the group consisting of radicals , , , and , n is 0, 1 or 2; R3 is a possible substituent, which in each case is selected from the group consisting of: -(C1-C6)alkyl, optionally substituted by (C3-C7)cycloalkyl; -OR4, (the meaning of the remaining radicals is given in claim 1), its corresponding N-oxide over the pyridine ring and pharmaceutically acceptable salts or solvates thereof. The compounds obtained are inhibitors of the phosphodiesterase 4 (PDE4) enzyme.EFFECT: increased efficiency.14 cl, 8 tbl, 19 ex
Triazolcarboxamide derivatives // 2637938
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula I. In formula IR1 is phenyl or pyridinyl optionally substituted by halogen, lower alkyl, lower alkoxy, lower alkyl, substituted halogen, and lower alkoxy substituted by halogen; X1 is -N = or CH; X2 is a CR2 or =N-; X3 is -N= or CH; provided that only two of X1, X2 or X3 are nitrogen; where is a triazole group selected from , or ; R2 is hydrogen or lower alkyl; Z is a bond, -O- or -CH2-. The compounds of the invention possess affinity for the receptors associated with trace amines (TAAR). The invention also relates to pharmaceutical compositions and to application of a compound for drug manufacture.EFFECT: new compounds of formula I are obtained that have a high affinity for the receptors associated with trace amines, especially TAAR1.12 cl, 1 tbl, 36 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

Heteroaryl compounds and their application // 2636584
FIELD: medicine, pharmacy.SUBSTANCE: present invention relates to new compounds selected from the group of compounds shown below, or pharmaceutically acceptable salts thereof, which have properties of kinase activity inhibitor selected from BTK, ErbB1, ErbB2, ErbB3, ErbB4, TEC, ITK, BMX and JAC3, or the said kinase mutant. At that, one or more kinases may be inhibited irreversibly by covalent cysteine (Cys) modification. The compounds may be used for treatment of rheumatoid arthritis, multiple sclerosis, diabetes, B-cell chronic or acute lymphocytic leukemia, hairy cell leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, colorectal cancer, pancreatic cancer, bone cancer, metastasis in the bone, osteoporosis, diabetes, irritable bowel syndrome, Crohn's disease, systemic lupus erythematosus or disorders associated with renal carcinoma transplant selected from breast cancer, glioblastoma, lung cancer, head and neck cancer, colorectal cancer, bladder cancer, non-small cell lung cancer, squamous cell carcinoma, salivary gland carcinoma, ovarian carcinoma, colorectal cancer or pancreatic cancer. Compounds are selected from the group of compounds , , , , , , , and compounds (I-382) - (I-393) specified in the invention formula.EFFECT: invention can be used to treat many diseases.16 cl, 25 dwg, 20 tbl, 302 ex

Cycloalkane derivative // 2635354
FIELD: pharmacology.SUBSTANCE: invention provides a compound represented by the formula , or a pharmacologically acceptable salt thereof, where Ar1 and Ar2: a heteroaryl group or an aryl group; R1, R2 and R3: a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a halogenated C1-C6 alkyl group or a cyano group; R4 and R5: a hydrogen atom, a halogen atom, a C1-C6 alkyl group, a hydroxyl group or a C1-C6 alkoxy group; N: an integer between 1 and 3; and the heteroaryl group or aryl group optionally contains one or two groups, independently selected from a halogen atom, a C1-C6 alkyl group, an amino group, and when a heteroaryl group or aryl group contains two such groups, the two groups are the same or different.EFFECT: increased efficiency of treatment.33 cl, 5 dwg, 8 tbl, 179 ex

New compounds for selective histone deacetylase inhibitors and pharmaceutical composition including such compounds // 2634694
FIELD: pharmacology.SUBSTANCE: invention relates to new compounds of formula I, their optical isomers or pharmaceutically acceptable salts that can be used for treatment of diseases mediated by histone deacetylase. In formula I, A is , Xa and Xb are CH, L1 and L2 independently hydrogen, -F, -Cl, -Br or -I, Q is C(=O), Y is selected from the group consisting of , and , M is C, O or N, l and m are independently 0 or 1, each of Ra1 and Ra2 is independently hydrogen; hydroxy; linear or branched -C1-4-alkyl, etc., n is 0, 1 or 2, Rb is hydrogen; hydroxy; linear or branched -C1-6-alkyl, etc., Z is selected from the group consisting of , etc., where each of Pa and Pb is independently ; hydrogen; hydroxy; linear or branched -C1-4-alkyl, etc., where is selected from phenyl, pyridine, pyrimidine, thiazole, indole, indazole, etc., each of x, y and z is independently 0 or 1, and each of Rg1, Rg2 and Rg3 is selected independently from hydrogen; hydroxy; -C1-3-alkyl, etc. The invention also relates to a pharmaceutical composition comprising compounds of formula I, a method for treatment of diseases mediated by histone deacetylase and application of said compounds for drugs preparation.EFFECT: increased effeciency of compound application.9 cl, 7 dwg, 16 tbl, 173 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

Dyetered diaminopyrimidine compounds and pharmaceutical compositions containing such connections // 2632907
FIELD: pharmacology.SUBSTANCE: invention relates to novel deuterated diaminopyrimidines of the general formula (I) and their pharmaceutically acceptable salts. In the general formula (I) R1a, R1b, R1c, R2a, R2b, R2c, R3, R4, R6, R7, R9, R10, R11, R12, R13a, R13b, R13c, R14a, R14b, R14c, R15a, R15b, R15c, R16, R17a, R17b, R18a, R18b, R19a, R19b, R20a and R20b independently hydrogen or deuterium; R5 is hydrogen, deuterium or halogen, R8 Represents a halogen; Provided that at least four of R1a, R1b, R1c, R2a, R2b, R2c, R3, R12, R13a, R13b, R13c, R14a, R14b, R14c, R19a, R19b, R20a or R20b are deuterium. The invention also relates to a process for the preparation of compounds of general formula (I) by reacting compound A6 with compound XV and to intermediates A6 and XV. In this case, in compound A6 R10, R11, R12, R13a, R13b, R13c, R14a, R14b, R14c, R15a, R15b, R15c, R16, R17a, R17b, R18a, R18b, R19a, R19b, R20a or R20b are independently selected from deuterium or hydrogen and at least one of them is deuterium; In compound XV R1a, R1b, R1c, R2a, R2b, R2c, R3, R4, R6, R7, R9 are independently selected from hydrogen or deuterium and at least one of them is deuterium; and R5 is hydrogen, deuterium or halogen; and R8 represents a halogen; X2 is selected from F, Cl, Br, I.EFFECT: compounds have ALK protein kinase inhibitory properties and can be used to treat or prevent cancer, impair cell proliferation, cardiovascular diseases, inflammation, infection, autoimmune diseases, organ transplantation, viral diseases, cardiovascular diseases or metabolic diseases.18 cl, 4 dwg, 1 tbl
Amide derivatives as ttx-s blockers // 2632899
FIELD: chemistry.SUBSTANCE: invention relates to the amide derivatives of formula ,where A is selected from the group consisting of phenyl, benzoimidazolyl, dihydroisoquinoline, indole, indazole, pyrazolyl, pyrazinyl, pyridazinyl, pyridyl, chinoline, sochinila and thiazolyl; B is selected from the group consisting of chemical bond, -C1-6alkylene-, -O-C1-6alkylene- and -NR7-; W is hydrogen or C1-6 alkyl; Z represents a nitrogen atom or CH; R1 represents a fluorinated substituent, independently selected from the group consisting of -CF3, -CHF2, -OCF3, -OCHF2, -OCH2CHF2, -OCH2CF3, -OCF2CHF2, -OCF2CF3, -OCH2CH2CF3, -OCH(CH3)CF3, -OCH2C(CH3)F2, -OCH2CF2CHF2, -OCH2CF2CF3, -OCH2CH2OCH2CF3, -NHCH2CF3, -SCF3, -SCH2CF3, -CH2CF3, -C (CH3)2CF3, -CH2CH2CF3, -CH2OCH2CF3, -OCH2CH2OCF3, 4,4-difluoropiperidino and (4-fluorobenzyl) oxy; R2 is independently selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -On-C1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R7, (7) -On-phenyl or -On-naphthyl, where specified phenyl or naphthyl is unsubstituted or substituted by one or more of the substituents independently selected from R7, and (10) -NR8R9; where n represents 0 or 1; if n=0, a chemical bond is present instead of-On-; p represents 1, 2, 3, or 4; if p is two or more than two, R2 may be the same or different; R3 and R4 independently represent hydrogen or C1-6 alkyl; R5 is independently selected from the group consisting of: (1) hydrogen, (2) halogen, and (3) -On-C1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R7, where n represents 0 or 1; if n=0, a chemical bond is present instead of -On-; q represents 1, 2, or 3; if q is equal to two or more than two, R5 may be the same or different; R6 independently represents hydrogen, C1-6 alkyl, C2-6alkenyl, C3-7 cycloalkyl, phenyl, or heterocyclic group, which is unsubstituted or substituted by one or more of the substituents independently selected from halogen, hydroxyl, C1-6alkyl and -O-C1-6 alkyl; R7 is selected from the group consisting of: (1) hydrogen, (2) halogen, (3) hydroxyl, (4) -(C=O)m-Ol-C1-6 alkyl, where specified alkyl is unsubstituted or substituted by one or more of the substituents independently selected from R10, (9) -(C=O)m-Ol-heterocyclic group, where this heterocyclic group is unsubstituted or substituted by one or more of the substituents independently selected from R10, and (11) -NR8R9, where l=0 or 1 and m=0 or 1; if l=0 or m=0, a chemical bond is present instead of-Ol- or -(C=O)m -, and if l=0 and m=0, a chemical bond is present instead of -(C=O)m-Ol-; R8 and R9independently represent hydrogen or C1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from halogen, hydroxyl, C1-6alkyland -O-C1-6 alkyl; or R8 forms a 4-7-membered ring with R9, which may contain a nitrogen atom, an oxygen atom, a sulfur atom, a carbonyl or a double bond, where a 4-7-membered ring is not optionally substituted with 1-6 substituents independently selected from the group consisting of: (1) hydrogen, (2) hydroxyl, (3) halogen, (4) C1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from R10, and (6) -O-C1-6 alkyl, which is unsubstituted or substituted by one or more of the substituents independently selected from R10; R10 is independently selected from the group consisting of: (1) hydrogen, (2) hydroxyl, and (3) halogen, which possess activity relative to blocking the potential-dependent sodium channels, such as TTX-S.EFFECT: method for producing amido derivatives is improved.14 cl, 3 tbl

Pyridon derivatives // 2632885
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) . New compounds and their crystalline forms that inhibit Ax1 and are useful for treatment of diseases caused by Ax1 hyperfunction, diseases associated with Ax1 hyperfunction, and/or diseases accompanied by Ax1 hyperfunction, such as hyperoproliferative disease.EFFECT: means have increased effectiveness.37 cl, 16 tbl, 107 ex, 16 dwg
Nitrogen-containing heterocyclic compound or its salt // 2632253
FIELD: chemistry.SUBSTANCE: invention relates to compound of the general formula [1]-(1): , where R2ais a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more substituents selected from a halogen atom; an amino-group; a C1-6alkylamino-group, which may be substituted by one or more halogen atoms, di(C1-6alkyl) amino-group, which may be substituted by one or more hydroxy-group, a C1-6alkylaminocarbonyl and di(C1-6alkyl) amino-group, or morpholinyl or piperazinyl group, which may be substituted by one or more substituents selected from hydroxy-group, a C1-6alkyl group and a hydroxy-C1-6alkyl group, R4a is a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more phenyl groups, R17a is a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more substituents selected from a halogen atom, the hydroxyl group, and a C1-6alkoxygroup, provided that R17a together with R4a, the nitrogen atom, to which R4a is attached, and the carbon atom, to which R17a is attached, may form a nitrogen-containing divalent azetidinyl, pyrrolidinyl, piperidinyl, or azepanyl group, which may be substituted by one or more substituents selected from the atom of the halogen atom, a hydroxyl group, a C1-3alkyl group or a C1-6alkoxy group; R17b and R18b are the same or different and are a hydrogen atom or a C1-6alkyl group, which may be substituted by one or more substituents selected from the atom of the halogen atom, a hydroxyl group and a C1-6alkoxy group, provided that R17b and R18b together with the carbon atom, to which they are attached, can form C(=O), or R17b and R18b together with the carbon atom, to which they are attached, may form a tetrahydropyrandyl group; R9a is a C1-6alkoxy group, pyrrolidinyl, piperidinyl, piperazinyl, pyrazolidine, triazoline, or morpholinyl group, which may be substituted by one or more substituents selected from the atom of the halogen atom and a C1-3alkyl group, or N(R15)(R16), where R15 is a hydrogen atom or a C1-6alkyl group, and R16 is a C1-6alkyl group, which may be substituted by one or more groups selected from a halogen atom, a cyano group, a C3-6cycloalkyl group, a phenyl group, which may be substituted by one or more halogen atoms, a C1-6alkoxy group, di(C1-6alkyl) amino-group, and a morpholinyl, a tetrahydropyranyl, or a thiophenol group, a C3-8cycloalkyl group, a phenyl group, which may be substituted by one or more groups selected from a halogen atom, a cyano group, a C1-6alkyl group, a C1-6alkoxy group, or a pyridinyl or chinolyl group, which may be substituted by one or more C1-6alkoxy group, or R15 and R16 may form a cyclic amino-group, which may be substituted by one or more groups selected from halogen and a C1-3alkyl group, and R12a is a C1-6alkyl group, which may be substituted by one or more groups selected from the hydroxy groups, di(C1-6alkyl) amino-group or a pyridinyl, a morpholinyl, or a pyrrolidinyl group, a phenyl group, which may be substituted by one or more groups selected from the halogen atom; a cyano group; an amino-group, which may be protected by the acyl group; a carbamoyl group, which may be substituted by one or more groups selected from the C1-6alkyl groups and the C3-8cycloalkyl group; a C1-6alkyl group, which may be substituted by one or more groups selected from halogen and the triazoline group; a C1-6alkoxy group, which may be substituted with halogen; or pyrazolidine, triazoline, or thiazolidine group which may be substituted by one or more groups selected from C1-6alkyl group and ceanography, or pyridyloxy, izohinolinove, talinolol, isoxazolidine, isothiazolinone, thiadiazolidine, indazolinone, benzothiazolyl, chinolyl, benzoxazolyl, or pyrazolopyrimidinyl group, which may be substituted by one or more groups selected from halogen, a C1-6alkyl group, which may be substituted by one or more C1-6alkoxy group, a C1-6alkoxy group, a C1-6alkyl amino-group, a C1-6alkoxy carbonyl group, or a morpholinyl group; X2a is a C1-6alkylene group, which may be substituted by one or more substituents selected from exography and the C1-6alkyl group, a divalent C2-6alicyclic hydrocarbon group, or a divalent aromatic hydrocarbon group, which may be substituted by one or more groups selected from halogen, a C1-6alkyl group, which may be substituted by halogen and the C1-6alkoxy group, and X3a is a C2-6alkynyl amino-group, or N(R22)-C(=O), where R22 is a hydrogen atom.EFFECT: compounds are an inhibitor of Fms-like tyrosine kinase 3, which can be used as a therapeutic agent for acute myelogenous leukemia.21 cl, 261 tbl, 70 ex

Aryl-or heteroaryl-substituted benzene compounds // 2632193
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula : , wherein X1 is N or CR11; X2 is N or CR13; Z is NR7R8 or CR7R8R14; Each of R1, R5, R9 and R10 is independently H or C1-C6 alkyl optionally substituted with one or more substituents selected from the group consisting of halogen and hydroxyl; Each of R2, R3 and R4 is independently -Q1-T1, wherein Q1 is a bond or a C1-C3 alkyl linker optionally substituted with halogen and T1 is H, halogen, hydroxyl or RS1, wherein RS1 is C1-C3 alkyl, C3-C8 cycloalkyl and RS1 is optionally substituted with one or more substituents selected from the group consisting of halogen and hydroxyl; R6 is C6-C10 aryl or a 5- or 6-membered heteroaryl containing 1 or 2 heteroatoms independently selected from N, O and S, each of which is optionally substituted with one or more -Q2-T2, wherein Q2 is a bond or C1 -C3 alkyl linker optionally substituted with halogen, and T2 is H, halogen, -NRaRb or RS2, wherein each of Ra and Rb is independently H or RS3, each of RS2 and RS3 is independently C1-C6alkyl, or 4-12 Membered heterocycloalkyl having 1 or 2 heteroatoms independently selected from N and O or Ra and Rb form together with N atom, to which they are attached, 4-12 membered heterocycloalkyl ring containing the heteroatom N and optionally containing 0 or 1 additional heteroatom selected from N or O; R7 is -Q4-T4 wherein Q4 is a bond or a C1-C4 alkyl linker optionally substituted with halogen and T4 is H or RS4 wherein each RS4 is C1-C6 alkyl, C3-C8 cycloalkyl or 4-12 membered heterocycloalkyl Containing one heteroatom selected from O or N and each of RS4 is optionally substituted with one or more -Q5-T5, wherein Q5 is a bond and T5 is H, halogen, C1-C6 alkyl, amino or mono-C1-C6alkylamino; Each of R8, R11, R12 and R13 is independently H, halogen, hydroxyl or RS6, wherein RS6 is C1-C6 alkyl or C3-C8 cycloalkyl, a 4- to 12-membered heterocycloalkyl containing 1 or 2 heteroatoms; or R7 and R8 form together with the N atom to which they are attached a 4-11 membered heterocycloalkyl ring containing 0-2 additional heteroatoms or R7 and R8 form together with the atom C to which they are attached a 4-11 membered A heterocycloalkyl ring containing from 1 to 3 heteroatoms; And R14 is absent or is H or C1-C6 alkyl optionally substituted with halogen, or a pharmaceutically acceptable salt thereof.EFFECT: compounds are used to treat cancer.61 cl, 12 dwg, 7 tbl, 201 ex
5-phenyl-substituted n-(tetrazol-5-yl)- and n-(triazol-5-yl)-amides of arylcarboxylic acids, as well as their use as herbicides // 2629952
FIELD: chemistry.SUBSTANCE: invention relates to 5-phenyl-substituted N-(tetrazol-5-yl)- and N-(triazol-5-yl)-amides of arylcarboxylic acids of formula (I) or their salts: . In formula (I), A is N or CY, B is N or CH, X is halogen, (C1-C6)-alkyl, OR1 or NR1COR1, Y is hydrogen, halogen, (C1-C6)-alkyl, COOR1, OR1, S(O)nR2, N(R1)2, (C3-C6)-cycloalkyl-(C1-C6)-alkoxy, azetidin-2-one-1-yl or pyrazol-1-yl, Z is halogen, cyano, halo- (C1-C6)-alkyl, S(O)nR2, (C1-C6)-alkyl-OR1 or Z can also be hydrogen if Y is the residue of S(O)nR2, W is (C1-C6)-alkyl, (C1-C6)-alkoxy or halogen, R is (C1-C8)-alkyl which is substituted by s-number of residues selected from the group consisting of (C1-C6)-alkoxy, R1 is hydrogen, (C1-C6)-alkyl or halo-(C1-C6)-alkyl, R2 is (C1-C6)-alkyl, n is 0, 1 or 2, and s is 0 or 1. The invention also relates to a herbicide, a method of controlling undesirable plants and the use of compounds for controlling undesired plants.EFFECT: new compounds have been obtained that can be used as herbicides.6 cl, 3 tbl

Substituted benzene compounds // 2629118
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (Ie) or pharmaceutically acceptable salts thereof: where Z is NR7R8 or S(O)aR7, where a is 0; R1 is H or C1-C6 alkyl optionally substituted with one or more substituents selected from hydroxyl, C1-C6 alkoxy; Each of R2 and R4 is independently -Q1-T1, wherein Q1 is a bond or a C1-C3 alkyl linker optionally substituted with one or more substituents selected from halogen and hydroxyl, and T1 is H, C1-C3 alkyl; R3 is H or halogen; R5 is H or C1-C6 alkyl; R6 is H, halogen, -C(O)NRaRb or RS2, where RS2 is C1-C6 alkyl or 4-12 membered heterocycloalkyl containing from 0 to 3 heteroatoms in the ring selected from O, N or S, and Wherein each of Ra and Rb is independently H, C1-C6 alkyl or Ra and Rb together with the N atom to which they are attached form a 4-12 membered heterocycloalkyl ring containing 0 or 1 additional heteroatom selected from O, N or S; R7 is -Q4-T4, wherein Q4 is a bond or a C1-C4 alkyl linker and T4 is H, C1-C6 alkyl, C3-C8 cycloalkyl, C(O)-C1-C6 alkyl or 4-14 membered heterocycloalkyl, Containing 1 to 3 ring heteroatoms selected from O, N or S, each of which is optionally substituted with one or more -Q5-T5, wherein Q5 is a bond, C(O), C(O) NRk, NRkC(O) or a C1-C3 alkyl linker, wherein Rk is H or C1-C6 alkyl, and T5 is H, C1-C6 alkyl; R8 is H, C1-C6 alkyl optionally substituted with halogen or C1-C6 alkoxy, C2-C6 alkenyl, C3-C8 cycloalkyl or 4- to 7-membered heterocycloalkyl containing 1-3 heteroatoms in the ring selected from O, N or S; or R7 and R8 together with the N atom to which they are attached form a 4-12 membered heterocycloalkyl ring containing 0-2 additional heteroatoms selected from O, S or N and a 4-12 membered heterocycloalkyl ring that forms R7 and R8 is optionally substituted with one or more -Q6-T6, wherein Q6 is a bond or a C1-C3 alkyl linker and T6 is H, halogen, C1-C6 alkyl; and R12 is halogen, C1-C6 alkoxyl, C2-C6 alkenyl or C1-C6 alkyl optionally substituted with halogen.EFFECT: compounds are used to treat cancer.24 cl, 4 tbl, 47 ex

Aminomethyl quinolones useful ifor treatment of jnk-mediated disorder // 2629111
FIELD: chemistry.SUBSTANCE: invention relates to new aminomethyl quinolone derivative of formula (I) or its pharmaceutically acceptable salt, where R is -C(=O)A, -C(=O)OA, -C(=O)NHA, -C(=N-C≡N)A, -C(=N-C≡N)NHA or A; A is C1-6-alkyl, phenyl, lower cycloalkyl, adamantyl, heterocycloalkyl selected from benzodioxin, pyrrolidine, piperidine, morpholine or piperazine, heteroaryl selected from pyridine, pyrazole, thiazole, triazole or pyrimidine or bicyclic heteroaryl selected from quinoline, quinazoline, indole, benzothiazole, benzoimidazole or imidazopyridine optionally substituted with one or two A1; each A1 independently represents A2 or A3; each A2 is independently halo or oxo; each A3 is independently C1-6-alkyl, C1-6-alkoxy, phenyl, benzyl, heterocycloalkyl selected from morpholine, piperidine, diazepane, pyrrolidine, azepane or piperazine, bicyclic heterocycloalkyl selected from benzodioxole or diazobicycloheptane, heteroaryl selected from oxazole, triazole, pyrazole, imidazole, thiadiazole, oxadiazole, thiazole or tetrazole, amino, C1-6-alkylamino, C1-6-dialkylamino, amido, C1-6-alkyl ester group, sulfonyl, sulfonamido, -C(=O) or -C(═O)O, optionally substituted by one, two or three groups, selected from halo, hydroxy, C1-6-alkylamino, C1-6-alkyloxy, C1-6-alkyl, C1-6-alkoxy, phenyl, hydroxycycloalkyl wherein cycloalkyl is adamantyl, amino, C1-6-alkylamino, C1-6-dialkylamino, t-butyl complex of carbamic acid ester, (C1-6-alkyl) sulfonyl-piperidinyl or hydroxy- (C1-6-alkyl); R' is H or methyl; X is CX'; X' is H or halo; X1 is H, 2-oxazolyl, dimethylamido or C1-6-alkyl ester group; Y is CH or N; and Y1 is H, halo, C1-6- alkoxy or halo (C1-6alkyl). The invention also relates to particular aminomethyl quinolone derivatives and to the use of said aminomethyl quinolone derivatives.EFFECT: obtained new aminomethyl quinolone derivatives, useful in the treatment of JNK-mediated disorder.15 cl, 2 tbl, 211 ex

Amide compounds, methods for production, application as means for treatment and prevention of diseases caused by rna-containing viruses // 2628800
FIELD: pharmacology.SUBSTANCE: compounds of the invention are intended for manufacture of a pharmaceutical composition, kit or drug. The invention also relates to a process for preparation of compounds of the invention (versions). Compounds of the invention are intended for use in the prevention or treatment of diseases caused by RNA-containing viruses belonging to enteroviruses, metapneumoviruses or pneumoviruses.EFFECT: amide compounds for treatment or prevention of diseases caused by RNA-containing viruses.26 cl, 8 tbl, 5 ex
Hinuclidine ethers of 1-azaheterocylic acetic acid as antimuscarine means, method for their production and their drug compositions // 2628082
FIELD: pharmacology.SUBSTANCE: invention relates to formula compounds, where A can be a single bond, a double bond, O, S, NR3, C(R3)R4, CO, C(O)N(R3), N(R3)C(O) and C(R3)-(CH2)-C(R4); m is an integer from 1 to 4; N is 0 or an integer from 1 to 4; R1 is selected from the group consisting of phenyl and 5-member heteroaryl containing one S heteroatom optionally substituted by one or more substituents selected from the group consisting of halogen atoms, (C1-C6)alkyl and (C1-C6)alkoxy; X is a physiologically acceptable anion; R2 is a group of the formula (Y), where p is 0 or an integer from 1 to 4; Q is 0 or an integer from 1 to 4; P is absent or selected from the group consisting of CO, N(R3)C(O) and C(O)N(R3); W is selected from the group consisting of H, (C1-C10)alkoxyl, phenyl, heteroaryl optionally substituted with one or more substituents selected from the group consisting of halogen atoms, OH, oxo (=O), CO2R3, (C1-C6)alkyl, (C1-C6)alkoxyl and phenyl; wherein heteroaryl is a mono- or bicyclic ring system having from 5 to 9 ring atoms and from 1 to 3 heteroatoms selected from N, O and S; R3 and R4 are independently selected from the group consisting of H, halogen atoms, CONH2, (C1-C6)alkyl, (C1-C6)alkanoyl and (C3-C8)cycloalkyl, as selective M3 receptor antagonists, to a method for their preparation, to compositions containing them, and to their therapeutic use for treatment of a respiratory disease such as asthma and chronic obstructive pulmonary disease (COPD).EFFECT: increased composition application efficiency.14 cl, 2 tbl, 34 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
Sulfonamide compounds and their use as tnap inhibitors // 2627701
FIELD: chemistry.SUBSTANCE: invention relates to compounds of Formula I: wherein: Y1 is a bond and Y2 is -N(R6)-; L1 and L2 are each a bond; X1 is =N- or =C(R2)-; X2 is =N- or =C(R3)-; R1 and R4 are independently selected from the group consisting of -F, -Cl, -Br, -CN, -C(O)N(R7)-R8, -C(O)-O-R9, methyl, -OMe, -OCF3, optionally substituted phenyl and optionally substituted 5- or 6-membered heteroaryl; R2, R3 and R5 are hydrogen; R6 is hydrogen; R7 is hydrogen and R8 is selected from hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl or optionally substituted phenyl; either R7 and R8 together with the nitrogen atom to which they are attached form an optionally substituted heterocycloamino which is an optionally substituted pyrrolidine, an optionally substituted piperidine, an optionally substituted morpholine or an optionally substituted piperazine; R9 is selected from hydrogen, optionally substituted C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl or optionally substituted phenyl; A is selected from the group consisting of -C(O)-N(R7)-R8 or -C(O)-O-R9, or A is , R12 and R13 are independently selected from the group consisting of hydrogen, halogen, -CN, -OH, -C(O)-O-R19, optionally substituted C1-C4 alkyl, optionally substituted C3-C6 cycloalkyl optionally substituted with C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, optionally substituted phenyl and optionally substituted 5- or 6-membered heteroaryl, R19 is selected from the group consisting of hydrogen, optionally substituted C1-C4 lkila, C1-C4 haloalkyl, optionally substituted C3-C6 cycloalkyl and optionally substituted phenyl; and R15 represents hydrogen or C1-C4 alkyl; Wherein the substituted group is substituted by -CO2H, nitrile, hydroxyl, C1-C4 alkyl, C1-C4 alkoxy, phenyl, C3-C6 cycloalkyl or diC1-C4 alkylamine, which modulate TNAP activity.EFFECT: improved properties of compounds.14 cl, 1 tbl, 12 ex
Compounds of pyridazinamide and their use as synthetic syneckinasis inhibitors (syk) // 2627661
FIELD: chemistry.SUBSTANCE: invention relates to novel pyridazinamides of the formula I , where all variable substituents are defined in the claims, and their pharmaceutically acceptable salts, as well as a pharmaceutical composition based on them.EFFECT: compounds of the formula are SYK inhibitors and are useful for the treatment of autoimmune and inflammatory diseases.10 cl, 1 tbl, 43 ex

1-phenyl-2-pyridinylalkyl alcohols derivatives as phosphodiesterase inhibitors // 2626956
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of general formula , where: R1 is selected from the group consisting of: methyl; trifluoromethyl; R2 is selected from the group consisting of: methyl optionally substituted with cyclopropyl; cyclopentyl; or R1 and R2, together with their interconnecting atoms, form a 2,2-difluoro-1,3-dioxolane ring of formula (q) condensed with a phenyl group that carries -OR1 and -OR2 groups, where the asterisks indicate carbon atoms shared by such phenyl ring: , R19 is hydrogen; R3 is one or more substituents independently selected from halogen atoms; Z represents a -(CH2)n- group, where n is 0 or 1; A is a saturated and monocyclic (C3-C7) heterocycloalkylene group selected from the following list of di-radicals: , , , , , , , , , , where symbols [3] and [4] indicate the points of group A attachment to groups Z and K, respectively; K is selected from the group consisting of: -(CH2)mC(O)R4, where m can be 0 or 1; -C(O)(CH2)jR4, where j can be 1 or 2; -SO2(CH2)pR4, where p can be 0, 1 or 2; -(CH2)ySO2R4, where y can be 1 or 2; -(CH2)zR4, where z can be 1; and -C(O)(CH2)2SO2R4; R4 is a ring system which is a mono- or bicyclic ring which may be saturated, partially unsaturated or fully unsaturated, selected from phenyl, (C3-C8) cycloalkyl, (C3-C7) heterocycloalkyl where at least one ring carbon atom is replaced by a heteroatom selected from N, NH and O or heteroaryl, such ring is optionally substituted with one or more R5, which may be the same or different and which are independently selected from the group consisting of: (C1-C6) alkyl, optionally substituted with one or more groups independently selected from the list consisting of: -OH; (C3-C7) heterocycloalkyl(C1-C4)alkyl where at least one ring carbon atom is replaced by a heteroatom selected from N, NH, O; 5-6 member heteroaryl where at least one ring carbon atom is replaced by a heteroatom selected from N and O; -OR6 group, where R6 is selected from the group consisting of (C1-C6) haloalkyl; -SO2R7 group, where R7 is (C1-C4) alkyl; and methyl optionally substituted with one or more (C3-C7) cycloalkyls; halogen atoms; CN; NR8R9, where R8 and R9 are different or identical and independently selected from the group consisting of: H; (C1-C4) alkylen-NR13 R14, where R13 and R14 are different or identical and independently selected from the group consisting of: a (C1-C6) alkyl, or they form a saturated (C3-C7) heterocyclic ring together with the nitrogen atom to which they are attached; -SO2R15 group, where R15 is selected from the group consisting of: (C1-C4) alkyl; -C(O)OR17 group, where R17 is selected from the group consisting of: (C1-C6) alkyl; or they form, together with the nitrogen atom to which they are attached, a saturated or partially saturated heterocyclic ring which is optionally substituted by one or more (C1-C6) alkyl; (C1-C2) alkylene-NR8R9, as mentioned above; COR10, where R10 is (C1-C6) alkyl; oxo; -SO2R11, where R11 is (C1-C4) alkyl or NR8R9, where R8 and R9 are as above; -COOR12, where R12 is H, (C1-C4) alkyl or (C1-C4) alkylene-NR8R9, where R8 and R9 are as above; and -CONR8R9, where R8 and R9 are as above; where R6, R8, R9, R10, R11, R12, R13, R14, R15, R17 and R19 groups in each case may have the same or different value if more than one group is present; and their N-oxide derivatives on the pyridine ring or their pharmaceutically acceptable salts. The compound is a phosphodiesterase 4 (PDE4) enzyme inhibitors.EFFECT: improved properties.19 cl, 26 tbl, 36 ex
Derivatives of (3-methylpyrrolidin-3-yl)-methyl pyridinyl ether and their use as antagonists of receptor nk-3 // 2625798
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of the general formula Wherein A is taken from groups (a), (b) or (c): (a) or (b) or is cycloalkyl possibly substituted with a lower alkyl (c); Ar1 is phenyl or a six-membered heteroaryl containing one or two nitrogen atoms; X1 is N or CH; X2 is N-R1 or O; R1 is S(O)2-lower alkyl, C(O)-cycloalkyl, substituted with a lower alkyl, or is C(O)-lower alkyl, lower alkyl, cyano group, cycloalkyl or a six-membered heteroaryl containing one or two nitrogen atoms substituted with a lower alkyl, cyano group, C(O)-lower alkyl, halogen, lower alkyl substituted with halogen or lower alkoxy group, or is a phenyl substituted with a cyano group or halogen. R2 is a lower alkyl, halogen, pyrazolyl, 3-methyl-[1,2,4]oxazolyl, 5-methyl-[1,2,4]oxadiazol-3-yl, pyridyl substituted with a cyano group or is a phenyl substituted with a halogen or is a cyano group, lower alkoxy group or is piperidine-2-on. The invention may also relate to pharmaceutically active salts of the coumpound of the formula I.EFFECT: compounds are prospective antagonists of the NK-3 receptor for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety syndrome and attention deficit/hyperactivity disorder.12 cl, 1 tbl, 27 ex

New pyrazole derivative // 2625790
FIELD: pharmacology.SUBSTANCE: in particular, invention relates to a compound represented by the following general formula (I): [wherein Ar1 is 2-methoxy-4-(2-pyridylmethoxy)phenyl, etc. and Ar2 is 1H-indole-6-yl group, etc.] or to salt thereof.EFFECT: increased efficiency of treatment.19 cl, 4 dwg, 1 tbl, 112 ex

2-quinaldicarboxylic acid derivatives and their anti-influenza activity // 2624906
FIELD: pharmacology.SUBSTANCE: agent is amino acid derivatives of 2-quinaldicarboxylic acid: 2-quinaldine-seryl methyl ester (Qln-Ser), 2-quinaldine-tryptophanyl methyl ester (Qln-Trp) and 2-quinaldine-alanyl-proline-1(1-adamantyl)ethylamide (Qln-APR), and can be used for development of new antiviral drugs. The invention also relates to a new compound - 2-quinaldine-alanyl-proline-1(1-adamantyl)ethylamide (Qln-APR).EFFECT: increased antiviral activity of derivatives against influenza A viruses and acting on strains resistant to rimantadine and amantadine.3 cl, 7 dwg, 4 tbl, 6 ex
Heterocyclic compounds and their application as glycogen synthase kinase-3 inhibitors // 2623427
FIELD: chemistry.SUBSTANCE: invention relates to a heterocyclic compound of formula , where A represents NRB, where RB represents hydrogen; X1 and X2 represent CR2 and X3, X4, X5 and X6 represent CR3 or CR4, or X1 and X2 represent CR2, X3 represent N, and X4, X5 and X6 represent CR3; Y1, Y2, Y3 and Y4 represent CR4 or CR5 or Y2 represents N, and Y1, Y3 and Y4 represent CR5; provided that no more than one of Y1, Y2, Y3 and Y4 represents CR4; and provided that one of Y1, Y2, Y3 and Y4 represents CR4 or C-CF3, if none of X3, X4, X5 and X6 represents CR4; R1 represents hydrogen; each R2 represents hydrogen; each R3 is independently selected from the group consisting of hydrogen, CN, halogen, C1-C6-alkyl, C1-C6-haloalkyl, C1-C6-alkoxy and C1-C6-haloalkoxy; R4 represents a C-linked saturated or partially unsaturated monocyclic 5- or 6-member heterocyclic ring containing one heteroatom selected from O and N, as ring members, wherein the heterocyclic ring optionally has one N-linked substituent R8; R5 is selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C6-haloalkyl and C3-C7-cycloalkyl; and R8 is selected independently on the case from the group consisting of C1-C6-alkyl, C1-C6-haloalkyl and C1-C6-alkoxycarbonyl. The invention also relates to pharmaceutical compositions based on a formula (I) compound, formula (I) compound application, a method of treatment of diseases susceptible to treatment by a compound that modulates the activity of 3β glycogen synthase kinase.EFFECT: new heterocyclic compounds useful for treatment of neurodegenerative disorders or inflammatory diseases are obtained.25 cl, 2 tbl, 70 ex

N-acylhydrasone derivatives for application as selective inhibitors of t-cells and medicines for lymphoneoplasia treatment // 2622651
FIELD: pharmacology.SUBSTANCE: invention relates to new compounds of formula 1, its (E)-stereoisomer or a pharmaceutically acceptable salt: [Formula 1]. The compounds can be used to prepare pharmaceutical compositions for diseases prevention or treatment, where the disease is a "graft versus host" (GVH) response after organ transplantation or hematopoietic stem cells, multiple sclerosis, rheumatoid arthritis or lymphoneoplasia.EFFECT: new compounds with inhibitory activity against T-cells are obtained.8 cl, 16 tbl, 143 ex, 5 dwg
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

aleate salts of (e)-n-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and their crystal form // 2621719
FIELD: chemistry.SUBSTANCE: method of increasing neratinib oral absorption incudes neratinib administering to a patient in the form of maleate salt, where the neratinib maleate salt is a crystalline monohydrate of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide maleate (Form II). The invention also relates to a method for cancer treatment including neratinib administering to a patient in the form maleate salt (Form II).EFFECT: increased oral absorption and cancer treatment based on the use of a crystal form of neratinib maleate salt.7 cl, 8 dwg, 11 tbl, 2 ex

Crystalline solvates of hydrochloride 6-(piperidin-4-yloxy)-2h-isoquinolin-1-one // 2619129
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, in particular to crystalline dihydrate 6-(piperidin-4-yloxy)-2H-isoquinolin-1-one of formula and a solid pharmaceutical composition thereof.EFFECT: obtained crystalline hydrochloride dihydrate, having better stability and hygroscopicity, which is preferable in obtaining the medicinal product based on it.16 cl, 14 dwg, 1 tbl

Phenyl derivatives // 2619105
FIELD: chemistry.SUBSTANCE: invention relates to new compounds of general formula containing two cyclic groups, especially where M1 - Ring 1 and M2 - Ring 2, each independently represents a phenoxy group. The compounds have high antagonistic activity against human S1P2.EFFECT: invention due to its properties can be used as a therapeutic agent for the treatment of S1P2-mediated diseases such as diseases, resulting from vasoconstriction, fibrosis and respiratory diseases.8 cl, 6 dwg, 5 tbl, 45 ex

Solid forms of (1,1-dioxo-4-thiomorpholinyl) - [6 - [[3- (4-fluorophenyl) -5-methyl-4-isoxazolyl] methoxy] -3-pyridinyl] methanone // 2618524
FIELD: chemistry.SUBSTANCE: invention relates to the field of organic chemistry, in particular to a new solid form of the compound of formula (I). The invention also relates to a process for preparing of the said solid forms, pharmaceutical compositions based on the solid form, the use of solid forms of the compound (I) and a method of treating or preventing disorders associated with GABA A α5 receptor.EFFECT: invention provides obtaining of a new solid form of the compound (I), having improved stability, good bioavailability and low hygroscopic property.13 cl, 23 dwg, 7 tbl, 28 ex
Phenylpyrrole derivative // 2618228
FIELD: pharmacy.SUBSTANCE: invention relates to new derivatives of formula (I) Q: (A) or (B) phenylpyrrole, or pharmaceutically acceptable salts thereof, which are useful for prevention or treatment of diseases such as dementia, Alzheimer's disease, attention deficit, hyperactivity disorder, schizophrenia, epilepsy, "central" cramp, obesity, diabetes, hyperlipidemia, narcolepsy, idiopathic hypersomnia, behavior-induced insufficient sleep syndrome, sleep apnea syndrome, circadian rhythm, parasomnia, sleep-related traffic violation, insomnia and depression, or allergic rhinitis.EFFECT: increased compound application effeciency.13 cl, 3 tbl, 10 ex
New compounds and compositions for nampt inhibition // 2617988
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to the compound of IIB formula, or its pharmaceutically acceptable salts in which R represents a bicyclic nine-membered heteroaryl comprising 1, 2, 3 or 4 heteroatoms independently selected from N, S or O, wherein the said heteroaryl may be substituted by one or more substituents selected from the group consisting of oxo and halo; R1 is -NHR4 and R4 is 3-10 membered cycloalkyl, aryl selected from phenyl and tetrahydronaphthalene, or 9-10 membered heteroaryl containing 1 or 2 heteroatoms selected from N and O; 3-10 membered cycloalkyl; aryl selected from phenyl and naphthalenyl; or 5-10-membered monocyclic or bicyclic heteroaryl comprising one or two heteroatoms selected from N, O and S; R2 and R3 are hydrogen; values of other substitutes are specified in the invention formula; or where the compound is selected from a group consisting of compounds specified in the invention formula. Invention compounds have properties of nicotinamide phosphoribosyltransferase (NAMPT) inhibitor. The invention also refers to individual compounds selected from the group indicated in the invention formula, to the pharmaceutical composition, method of treatment, compounds application and application of the pharmaceutical composition.EFFECT: invention provides new compounds of IIB formula, with the properties of nicotinamide phosphoribosyltransferase inhibitor which can be used for hyperproliferative disorders treatment.33 cl, 4 tbl, 25 ex

Pyrazole compound and its pharmaceutical use // 2617678
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to a compound of general formula or pharmaceutically acceptable salt thereof. In formula (I) Cy represents phenyl, C3-8 cycloalkyl or C3-8 cycloalkenyl , Cya is a heterocyclic group with the structure given in the invention formula, R1a and R2b are groups defined in the formula. The objects of invention are also the pharmaceutical composition and the agent based on formula (I) compound, the method of diabetes treatment and prevention and compound application.EFFECT: invention is SGLT1 inhibitor and can be used to treat or prevent diabetes.24 cl, 4 tbl, 605 ex
Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as inhibitors // 2617401
FIELD: chemistry.SUBSTANCE: invention relates to compounds of general formula (I) (I), where: R1 and R2, which can be identical or different, independently selected from a group consisting of: - (C1-C6)alkyl, optionally substituted (C3-C7)cycloalkyl; - (C1-C6)halogenalkyl; - (C3-C7)cycloalkyl and - (C3-C7)heterocycloalkyl, containing heteroatom O; R3 represents hydrogen, (C1-C6)alkyl or (C1-C3)alkylthio(C1-C6)alkyl; A is a partially unsaturated or unsaturated bicyclic ring system consisting of two condensed monocyclic ring systems B and C, presented in cl. 1 of formula, where ring C is a monocyclic aryl or monocyclic heteroaryl ring system, ring B is a 5- or 6-member heterocycloalkyl group, zero of Y groups is bonded to ring C, n of groups Y is bonded to ring B, and n is an integer from 1 to 3; and where ring B and C optionally contains additional heteroatoms in amount of 1 to 4, selected from N, O or S; p is an integer from 0 to 3; Y denotes oxo group; K is selected from a group consisting of: - (C1-C6)alkyl, optionally substituted with one (C3-C7)cycloalkyl group; - (C3-C6)heterocycloalkyl(C1-C4)alkyl containing 1 or 2 heteroatoms selected from N or O; - (C3-C6)heterocycloalkyl containing 1 or 2 heteroatoms selected from N or O, optionally substituted with one or more (C1-C6)alkyl group; - (C1-C4)halogenalkyl; - OR4, where R4 selected from a group consisting of: - H; - (C1-C6)alkyl, optionally substituted (C3-C7)cycloalkyl or heteroaryl; - halogen atoms; - CN; - NO2; - NR5R6, where R5 and R6, which can be identical or different, independently selected from a group consisting of: - H; - OH; - (C1-C4)alkyl-NR7R8, where R7 and R8, which can be identical or different, independently selected from a group consisting of: H; (C1-C6)alkyl, possibly substituted (C1-C6)alkoxyl; and (C1-C6)alkyl-NR9R10, where R9 and R10, which can be identical or different, represent H or (C1-C6)alkyl; or they form together with a nitrogen atom to which they are bonded, (C3-C6)heterocycloalkyl ring containing 1 or 2 heteroatoms, selected from N, O or S, optionally substituted (C1-C6)alkyl or (C1-C6)alkylcarbonyl group; -(C1-C6)alkyl, optionally substituted with (C1-C6)alkoxyl or heteroaryl, (C3-C6)heterocycloalkylcarbonyl containing 1 or 2 heteroatoms selected from N or O, heteroarylcarbonyl, wherein all of them may further be substituted with one or more (C1-C6)alkyl, (C1-C6)halogenalkyl or (C1-C6)alkoxyl groups, which are identical or different and are selected independently; - SO2R11, where R11 represents (C1-C6)alkyl; - C(O)R12, where R12 is (C1-C6)alkyl, optionally substituted with (C1-C6)alkoxyl; - (C1-C4)alkyl-NR13R14, where R13 and R14, which can be identical or different, are independently selected from a group consisting of groups: - SO2(C1-C6)alkyl, H, (C1-C6)alkyl and (C3-C7)heterocycloalkyl(C1-C4)alkyl containing 1 or 2 heteroatoms selected from N or O; and - SO2NR15R16, where R15 and R16, which can be identical or different, independently represent H or (C1-C6)alkyl; where groups with R4 at R16 have similar or different values in each case, if they are present in more than one group; and where heteroaryl is a mono- or bicyclic ring system with 5–10 ring atoms, containing 1 or 2 heteroatoms selected from N, O or S; or its pyridine-N-oxides, pharmaceutically acceptable salts or solvates. As well as to methods of producing such compounds, compositions containing them and their therapeutic application as inhibitors of phosphodiesterase 4 (PDE4) enzyme.EFFECT: disclosed are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols as inhibitors.16 cl, 16 tbl, 52 ex
orpholino-substituted derivatives of urea or carbamate as mtor inhibitors // 2616619
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of formula (I) , where m equals 1 or 2; n equals 0, 1 or 2; each of R1 is independenly selected from the group consisting of C1-6alkyl, where C1-6alkyl is probably substitued with one R3; probably, two R1 are joint with a ring to which they are attached to form 8-membered heterobicycle; R3 is OR4; R4 is H; T0 is phenyl where T0 is substituted with the group N (R5a) C(O) N (R5bR5); R5a, R5b are independently selected from the group consisting of H; R5 is T2 or C1-6alkyl, where C1-6alkyl is probably substituted with 1-4 R8, which are the same or different; R8 is halogen; OR9; N (R9R9a); R9, R9a are independently selected from the group consisting of H; T2 is C3-7cycloalkyl; 4-6-membered heterocyclyl, wherein 1 circular atom is substituted with oxygen heteroatom; 6-membered aromatic heterocyclyl, wherein 1 circular atom is substituted with nitrogen heteroatom; and phenyl, wherein T2 is probably substituted with one or two R10, which are the same or different; R10 is halogen; OR11; or C1-6alkyl, where C1-6alkyl is probably substituted with one R12; R11 is H; R12 is OR13; R13 is H; T1 is phenyl or 6-membered aromatic heterocycle, wherein 1 carbon atom is substituted with nitrogen heteroatom, wherein T1 is substituted with a group S(O)2R14 and is probably additionally substituted with one R15; R15 is halogen; R14 is C1-6alkyl or unsubstituted 5-membered heterocyclyl ring, wherein 1 circular atom is substituted with nitrogen heteroatom. Compounds of formula (I) possess mTOR inhibitory activity. The invention also relates to a pharmaceutical composition, to compound application for drug manufacture and to a treatment method.EFFECT: new compounds of formula are obtained, which are useful for treatment or prevention of mTOR-related diseases and disorders.21 cl, 6 tbl, 44 ex
Novel compounds and compositions for inhibiting nampt // 2616612
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula IB: (IB), where Ar is phenyl or benzyl; R1 denotes -NRaRb, where Ra denotes H, and Rb denotes phenyl; 5-9-member heterocycloalkyl, containing 1 or 2 heteroatoms, independently selected from N or O; 6-10-member aryl; 5-14-member heteroaryl containing 1 or 2 heteroatoms, independently selected from N, S or O; each of said heterocycloalkyl, aryl or heteroaryl is not substituted or is substituted with 1 or 2 substitutes, which can be identical or different, and are independently selected from a group consisting of deuterium, halogen, cyano, C1-C6-alkyl, hydroxyl, hydroxyalkyl, hydroxyalkoxy, halogen-C1-C6-alkyl, alkoxy, halogen-C1-C6-alkoxy, -(CH2)q-NRcRd, -(CH2)q-CONRcRd, -S(O)2-C1-C6-alkyl, -S(O)2NH2, -C(O)O-C1-C6-alkyl, phenyl, 5-member -(CH2)qheteroaryl, containing 1 or 2 heteroatoms, independently selected from N, and 5-6-member -(CH2)qheterocycloalkyl containing 1 or 2 heteroatoms, independently selected from N or O, wherein each of said heterocycloalkyl or heteroaryl can be substituted with one or more halogen, nitro, halogen-C1-C6-alkyl, halogenalkoxy, oxo, cyano, C1-C6-alkyl or alkoxy, and Rc and Rd are independently selected from a group, consisting of H, C1-C6-alkyl and 3-5-member cycloalkyl; q is equal to 0; for inhibiting NAMPT, their synthesis, use and antidotes.EFFECT: novel compounds and compositions for inhibiting NAMPT.26 cl, 3 tbl, 8 ex
Process for preparation of 1-acyl-4-phenylsulfonylprolinamide derivatives and new intermediates // 2615997
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing proline of formula 1, where R1 is selected from C1-7-alkyl or a radical of formula II, where R4 is selected from a group, containing C1-7-alkyl, halogen-C1-7-alkyl and phenyl, optionally substituted by halogen; R2 is selected from a group, containing halogen or halogen-C1-7-alkyl; and R3 is selected from a group, containing hydrogen, halogen, halogen-C1-7-alkyl, C1-7-alkoxy, halogen-C1-7-alkoxy or 5-or 6-member heterocycle, containing one or two nitrogen atoms, wherein cycle is optionally substituted with C1-7-alkyl or halogen, and a novel intermediate compound used in method.EFFECT: proline derivatives of formula 1 are preferable inhibitors of cysteic cathepsin protease S and are therefore useful in treating metabolic diseases, such as diabetes, atherosclerosis, abdominal aortic aneurysm, peripheral artery disease and diabetic neuropathy.29 cl, 1 ex
Tetrahydroquinoline derivatives as activators of ampk // 2615758
FIELD: chemistry.SUBSTANCE: invention relates to a new tetrahydroquinoline derivative of formula or its pharmaceutically acceptable salt, wherein R1: hydrogen, lower alkyl, halogen or carboxy; R2: hydrogen, lower alkyl, halo-lower alkyl, halogen, cyano, or carboxy; R3 and R4: lower alkyl; R5 and R6 are selected from hydrogen, carboxy-lower alkylamino, carboxycyclopropylamino, lower alkylsulfonylamino, phenylsulfonylamino, halophenylsulfonylamino, lower alkylphenylsulfonylamino, halophenylkarbonilamino, piridinilsulfonilamino, lower alkylaminosulfonyl and halophenylaminosulfonyl; with the provision that both R5 and R6 do not simultaneously represent hydrogen; R7: hydrogen or lower alkyl. The invention also relates to the pharmaceutical composition based on the compound of the formula (I) and to the application of the compound of the formula (I).EFFECT: invention provides obtaining new tetrahydroquinoline derivatives useful as an activator of AMP-activated protein kinase (AMPK).20 cl, 1 tbl, 94 ex
 
2551327.
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