Ortho-condensed systems (C07D487/04)

ethod of producing trans-1,4,5,8-tetranitroso-1,4,5,8-tetraazadecalin // 2642470
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing trans-1,4,5,8-tetranitroso-1,4,5,8-tetraazadecalin by the condensation of glyoxal with ethylenediamine in the presence of sodium nitrite and acetic acid with subsequent dosage of the reaction mixture in dilute mineral acid, in which 30-40% sulfuric acid is used as mineral acid, and p-toluensulfonate is introduced into a mixture of glyoxal, ethylene diamine, sodium nitrite, acetic acid.EFFECT: development of highly effective environmentally safe way of obtaining a compound.2 cl, 1 tbl, 8 ex

7-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine as activator of glucokinase and inhibitor of dipeptidyl peptidase of type 4 and method of its production // 2642432
FIELD: chemistry.SUBSTANCE: invention relates to 7-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-[1,2,4]triazolo [1,5-a]pyrimidine as an activator of glucokinase and an inhibitor of dipeptidyl peptidase of type 4: . The invention also relates to the method of its production.EFFECT: new compound is produced that can be used as an activator of glucokinase and an inhibitor of dipeptidyl peptidase of type 4.2 cl, 3 dwg, 3 ex
ethod of producing 6-ethoxycarbonyl-7- (thien-2-yl) -5-methyl-4,7-dihydro-1,2,4-triazolo [1,5-a]pyrimidine that has high tuberculostatic activity // 2642420
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing 6-ethoxycarbonyl-7-(thien-2-yl)-5-methyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine having tuberculostatic activity of the formula , which consists in interaction of 2-thiophenaldehyde, acetoacetic ester and 3-amino-1,2,4-triazole by heating in a solvent, where water is used as the solvent, with a molar ratio water: 2-thiophenaldehyde: acetoacetic ester: 3-amino-1,2,4-triazole is 55:1:1:1.EFFECT: new simple technological method of obtaining a compound that does not require special equipment and acids and large volumes of organic solvents is developed.3 ex
Sodium salt of 3-nitro-4-oxo-1,4-dihydropyrazolo[5,1-c]-1,2,4-triazine-8-carboxylic acid, dihydrate // 2641107
FIELD: chemistry.SUBSTANCE: invention relates to sodium salt of 3-nitro-4-oxo-1,4-dihydropyrazolo[5,1-c]-1,2,4-triazine-8-carboxylic acid, dihydrate, .EFFECT: new compound showing antiglating properties is produced.2 tbl, 3 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
New compounds // 2640200
FIELD: pharmacology.SUBSTANCE: invention relates to a new compound of the formula (I) or a pharmaceutically acceptable salt thereof having interferon α (IFN-α) and tumour necrosis factor α (TNF-α) inducer properties. The compounds may be useful as vaccine adjuvants. In the formula (I) R1 is n-C3-6alkyl; R2 is hydrogen or methyl; R3 is hydrogen or C1-6alkyl; m is an integer having a value of 1 to 4.EFFECT: compounds can be used for treatment of allergic diseases and inflammatory conditions, for example, allergic rhinitis and asthma, infectious diseases and cancer.15 cl, 7 ex

Derivatives of azaindasole or diazaindasole type for pain treatment // 2640046
FIELD: pharmacology.SUBSTANCE: invention relates application of a compound of formula for treatment or prevention of pain associated with at least one Trk protein. The radicals and symbols in formula (I) have the definitions indicated in the claims. The invention also relates to a pharmaceutical composition comprising a compound of formula (I) as an active substance.EFFECT: compound application efficiency increase.15 cl, 6 dwg, 1 tbl, 35 ex
Derivatives of 1h-pyrazolo [3,4-d] pyrimidine and method of their production // 2638928
FIELD: chemistry.SUBSTANCE: invention relates to novel derivatives of 1H-pyrazolo [3.4-d] pyrimidine of the general formula I , where: R=CH3, R1=C(O)NH (Ia); R=CH3, R1=C(NH)NH2 (Ib); R=naphthylmethyl, R1=C(O)NH2 (Ic); R=naphthylmethyl, R1=C(NH)NH2 (Ir). Derivatives of 1H-pyrazolo[3,4-d]pyrimidine presented in the formula I, are produced by the interaction of 4,6-dichloro-2-S-(substituted) pyrimidine-5-carbaldehyde dissolved in tetragidrofurane, with the addition of the calculated derived quantities of hydrazine and triethylamine in a molar ratio of 1:1:2, the mixture is mixed on the magnetic agitator for 12 h at room temperature. The resulting precipitate is poured with water and stirred at room temperature for 3 hours. The regenerated precipitate is filtered.EFFECT: production of new compounds that can be used for the synthesis of heterocyclic compounds and in medicine as antimicrobial agents.2 cl, 2 tbl, 5 ex
Pyrazolaminopirimidine derivatives as leucine-repeating kinase 2 (lrrk2) modulators for treatment of parkinson disease // 2637948
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the formula or to their pharmaceutically acceptable salts, wherein X, R1, R2, R3 and A are as defined in the claims. The compounds of formula (I) are modulators of leucine-repeating kinase 2 (LRRK2) modulators.EFFECT: application fortreatment of diseases associated with the LRRK2 receptor, such as Parkinson's disease.20 cl, 2 tbl, 53 ex
Derivatives of isoindole [2,1-a]chinazoline for stabilizing organic materials // 2637807
FIELD: chemistry.SUBSTANCE: invention relates to a composition comprising a) an organic material susceptible to oxidative, thermal, or light degradation, which is a polymer, an oligohydroxy compound, wax, fat or mineral oil, provided that the polymer is not polypeptide, agar-agar, or an agar- agar component, and the oligohydroxy compound is not glucose or an agar-agar component; b) a compound of formula I, wherein n is 1, R5 is H, C1-C12-alkyl, C6-cycloalkyl, C6-aryl, OH, C1-alkoxy, C7-aralkyloxy, R1-R4 and R6-R9 each is independently of one another, H, C1-alkyl, C1-alkoxy, halogen; c) an additional additive, which is a phenolic antioxidant; and d) the second additional additive, which is phosphite. The invention also relates to the use of the said composition, a method of protecting an organic material, a compound of formula , and an additive composition based on a compound of formula (I).EFFECT: composition is produced useful for protecting an organic material susceptible to oxidative, thermal, or light degradation.15 cl, 7 tbl, 23 ex
Hydrohalogenide of 1-(3,4-dimethoxyphenyl)-2-(7,8-dimethyl-2,3,4,5-tetrahydro-1,3]diazepino[1,2a]benzimidazole-11-yl)ethanone with analgesic and anxiolytic activity // 2636785
FIELD: pharmacology.SUBSTANCE: invention relates to organic chemistry, namely to a hydrohalogenide of 1-(3,4-dimethoxyphenyl)-2-(7,8-dimethyl-2,3,4,5-tetrahydro[1,3]diazepino[1,2-a]benzimidazole-11-yl)ethanone of formula 1 , which has both analgesic and anxiolytic activity.EFFECT: new heterocyclic compound possessing the effective biological properties is obtained.2 cl, 3 tbl, 1 ex

Aminopyrimidine kinase inhibitors // 2636589
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula 2 , wherein independently for each case R1 is hydrogen; each R2 and R3 is independently selected from the group consisting of hydrogen; (C1-C6)alkyl, optionally substituted with OH; heteroaryl containing 6 atoms in the ring, 1 atom of which is N, and the remaining ones are C atoms (pyridine); heterocyclyl containing 5 or 6 ring atoms, 1 atom of which is N and the remaining ones are C atoms (piperidine or pyrrolidine) optionally substituted by a group selected from methyl, phenyl, pyridinylmethyl, quinolinylmethyl, pyridinylmethyl, piperidinylmethyl or azetidinylmethyl; aryl (C1-C6)alkyl, wherein aryl contains 6 ring atoms, optionally substituted amino or CH2NH2, where (C1-C6)alkyl is optionally substitutedby OH; heteroaryl (C1-C6)alkyl, wherein heteroaryl contains 5 to 9 ring atoms, of which 1 to 2 are heteroatoms selected from N and S, and the remaining atoms are C atoms (indole, pyridine, thiophene, benzimidazole, pyrazole), wherein heteroaryl is optionally is replaced by ethyl; heterocycle (C1-C6)alkyl, wherein the heterocycle contains 6 ring atoms, 1 atom of which is N and the remaining ones are C atoms (piperidine) optionally substituted by methyl; and - [C(R4)2]p-R5, or R2 and R3 are joined together to form an optionally substituted heterocyclic ring containing 5-10 atoms, of which 1 to 2 are heteroatoms selected from N and O, and the remaining ones are C atoms; R20 is selected from the group consisting of hydrogen; heterocyclyl containing 6 ring atoms, 1 atom of which is a heteroatom selected from N, and the remaining atoms are C atoms (piperidinyl); halogen (C1-C6)alkyl; trifluoromethyl; fluorine (C1-C6)alkyl; -O-[C(R4)2]p-R5; -OR16, where R16 is methyl; and amino, which is -N(R50)(R51), where each R50 and R51 is independently hydrogen, (C1-C6)alkyl, optionally substituted by methoxy, or - (CH2)m-R61, where R61 is an aryl containing 6 ring atoms, and m is an integer from 1 to 8. The invention also relates to specific compounds as defined in the claims. The compounds of the invention are for cancer treatment or effect on apoptosis, by administration of a therapeutically effective amount of a compound to a mammal in need thereof.EFFECT: aminopyrimidine compounds for cancer treatment.24 cl, 30 tbl, 251 ex, 53 dwg

Polymorphs of kinase inhibitor // 2636588
FIELD: chemistry.SUBSTANCE: invention relates to polymorphic form A of compound formula .EFFECT: new polymorphic form of compound I is produced, which has improved properties, such as, for example, stability, hygroscopicity, useful in the treatment of mTOR-associated disorder.18 dwg, 7 tbl, 13 ex
Imidazo[1,2-b]pyridazine derivatives as kinase inhibitors // 2635917
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of the general formula having an imidazo[1,2-b]pyridazine structure, or a pharmacologically acceptable salt thereof and a pharmaceutical composition comprising such a compound. In the formula R1, G, T, Y1, Y2, Y3 and Y4 have values indicated in the claims.EFFECT: compounds of the formula are useful for treatment of a tumour through an inhibitory effect on the enzymatic activity of its ROS1 kinase and the inhibitory effect on the enzyme kinase NTRK.48 cl, 25 tbl, 150 ex
ethod of producing 2-amino-5,8-dimethoxy[1,2,4]triazolo[1,5-c]pyrimidine from 4-chloro-2,5-dimethoxypyrimidine // 2635352
FIELD: chemistry.SUBSTANCE: invention relates to the method of producing 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c]pyrimidines of formula (I), where R is C1-C4 alkyl that comprises i) contacting 4-chloro-2,5-dialkoxypyrimidine of formula with cyanamide salt in a polar aprotic solvent to produce 2,5-dialkoxy-4-cyanoaminopyrimidine of formula ; ii) contacting 2,5-dialkoxy-4-cyanoaminopyrimidine with hydroxylamine either as a free base or as hydroxylamine salt in the presence of a base to produce 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine of formula ; and iii) cyclizing 2,5-dialkoxy-4-hydroxyguanidinyl pyrimidine by treatment with alkyl chloroformate to produce 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c]pyrimidine (I). The invention also relates to the method of producing 2-amino-5,8-dialkoxy[1,2,4]triazolo[1,5-c] pyrimidines of formula (I) by cyclizing 2,5-dialkoxy-4-hydroxyguanidinylpyrimidine; and to the compounds of formula , .EFFECT: simplifying the technology for the production of a compound of formula I without the use of hydrazine and halogeno cyan.22 cl, 6 ex
Substituted derivatives of 3-heteroaroylaminopropionic acid and their application as drugs // 2632897
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula I in any of its stereoisomeric forms or a physiologically acceptable salt thereof, wherein A is selected from the group consisting of C(R1) and N; D is selected from the group consisting of C(R2) and N; E is selected from the group consisting of C(R3) and N; L is selected from the group consisting of C(R4); where at least one and not more than two of A, D, E or L is N; G is selected from the group consisting of R71-O-C(O)-;R1 is selected from the group consisting of hydrogen, halogen; R2 is selected from the group consisting of hydrogen, halogen, (C1-C7)-alkyl, Het2 and Ar-CsH2s-, where s is 0; R3 is selected from the group consisting of hydrogen, Het2, R11-O-; R4 and R10 are selected from the group consisting of hydrogen, halogen; provided that one of the R2, R3 is a cyclic substituent; R11 is selected from the group consisting of hydrogen, R14; R12 and R13 are hydrogen; R14 is (C1-C10)-alkyl optionally substituted by one substituent, which is an oxo group; R30 is selected from the group consisting of R31, R32-CuH2u-, where u is 0; R31 is (C1-C10)-alkyl; R32 is phenyl, wherein phenyl is optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-O-, CF3-; R40, R50, R60 and R71 are hydrogen; Ar, independently of other Ar groups, is selected from the group consisting of phenyl and aromatic 5-membered or 6-membered monocyclic heterocycle which includes one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur, and is bonded through the carbon atom of the ring, wherein phenyl and heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, HO-(C1-C6)-alkyl, Het4, (C1-C6)-alkyl-O-, -CF3, -CO-(C1-C6)-alkyl, -CO-NR12R13 and NC-; and wherein phenyl can be substituted with -CH=CH-CH=CH-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CF2-O- or -N((C1-C3)-alkyl) -CH=CH-; Het2 is a saturated 5-membered - 6-membered monocyclic heterocycle that includes a nitrogen atom in the ring through which Het2 is attached and optionally one other ring heteroatom selected from the group consisting of nitrogen and oxygen; Het4, regardless of other Het4 groups, is a saturated or unsaturated 4-membered to 5-membered monocyclic heterocycle that includes one to three ring heteroatoms selected from the group consisting of nitrogen and oxygen which is optionally substituted by one or more identical or different substituents selected from the group consisting of (C1-C4)-alkyl, HO-, (C1-C4)-alkyl-O-. Compounds of formula are obtained by the reaction of a compound of formula II with a compound of formula III, where the A, D, E, L, G, R10, R30, R40, R50 and R60 groups such as defined above for compounds of formula I, and additional functional groups may be present in protected form or in the form of a precursor group, and group J in the compound of formula II is HO-, (C1-C4)alkyl-O- or halogen.EFFECT: substituted derivatives of 3-heteroaroylaminopropionic acid for application as a pharmaceutical agent for catheptase protease A inhibition.10 cl, 1 tbl, 620 ex
Pyrrolopyrimidine compounds for malignant tumour treatment // 2631655
FIELD: pharmacology.SUBSTANCE: in formula I , one of X and X' is N, and the other X and X' is C; one of the dashed lines in formula I is a single bond, and the other dashed line in formula I is a double bond; R1 is phenyl which may be substituted with 1 to 2 substituents selected from halogen atoms, S(O)2R, where R is a 5-6-member cycloalkyl in which one CH2 group is optionally replaced by an oxygen atom; NRaRb, -CH2NRaRb, 1,1-cyclopropyl-NRaRb, S(O)2NRaRb, wherein each Ra and Rb are hydrogen or both Ra and Rb are 4-6-member heterocycloalkyl which may further contain NH, N-CH3, O (oxygen) as a heteroatom and may be substituted by halogen atoms; R2 is -R5'R6, where R5' is a covalent bond or C1-C3alkyl, and R6 is C6cycloalkyl, and wherein R6 is optionally substituted one to two times with independently selected polar groups selected from amino or hydroxy; R3 is -NR7R8, where one of R7 and R8 is selected from H, C1-C6alkyl, and the other R7 and R8 is selected from C1-C6alkyl, C3-C6thcycloalkyl-C1-C6alkyl, each of which is optionally substituted once with a polar group selected from hydroxy; or R2 and R3 together form a linking group, wherein the linking group is -NH-(CH2)4-C(=O)-NH-(CH2)3-, R4 is H and R5 is H or a pharmaceutically acceptable salt thereof. The compounds are selected from IA or IB structure, where R1-R5 have the values indicated in paragraph 1.EFFECT: possibility to use for treatment of a malignant tumour selected from the group consisting of myeloid leukemia, lymphoblastic leukemia, melanoma, malignant breast, lung, colon, liver, stomach, kidney, ovary, uterus and brain.14 cl, 3 tbl, 5 ex

Cytotoxic benzodiasepine derivatives // 2631498
FIELD: pharmacology.SUBSTANCE: invention relates to a cytotoxic compound of formula or pharmaceutically acceptable salts thereof. In the formula (IA), the double line between N and C is a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H and Y is -SO3M; M is -H, Na+ or K+, A and A' are both -O-, R6 is -OR, wherein R is a linear alkyl having from 1 to 6 carbon atoms; X' is -H, Y' is -H, L' is -W'-RX-V-RY-J, wherein W' and V are the same or different and each is independently absent or selected from -O-, -S-, -CH2-S-, -N(Re)-, -N(Re)-C(=O)- and -SS-; Rx and Ry are the same or different and each is independently absent or is optionally substituted by a linear or branched alkyl having from 1 to 10 carbon atoms, optionally substituted by -SO3H; Re is selected from -H, linear, branched alkyl having from 1 to 10 carbon atoms, or -(CH2-CH2-O)n-Rk, wherein Rk is -H, a linear, branched alkyl having from 1 to 6 carbon atoms; n is an integer from 1 to 3; and J includes a reactive group bonded thereto and is selected from -SH, -COOH and -COE, wherein -COE is an N-hydroxysuccinimide ester; L" and L"' are -H, and G is -CH-. The invention also relates to a conjugate comprising a cytotoxic compound and an antibody, to methods for cancer treatment in a mammal.EFFECT: new compounds have been obtained that can be used as antiproliferative agents.37 cl, 60 dwg, 10 tbl, 32 ex

New method of synthesis of tetrahydropyrasin[2,3-c]pyridazine derivatives // 2631430
FIELD: pharmacology.SUBSTANCE: invention relates to a method for synthesis of tetrahydropyrazino[2,3-c]pyridazine derivatives of the formula , which can be used for manufacture of medicaments for treatment of oncological, chronic inflammatory and other diseases.EFFECT: new synthesis method allows to obtain compounds of general formula 1 possessing an increased degree of purity.7 cl, 6 dwg, 5 ex

New compounds - neurokinin 1 receptor antagonizer // 2631319
FIELD: pharmacology.SUBSTANCE: in formula n=1 or 2; R1 and R2, independently of each other, are hydrogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy or halogen; R3 is hydrogen or C1-4 alkyl optionally substituted with hydroxy; R4 is hydrogen or oxo; R5 and R6, independently of one another, are hydrogen, C(=O)OR7, C(=O)NR8R9, C1-4 alkyl, wherein the said C1-4 alkyl is optionally substituted with hydroxy, NR8R9 or a 5- or 6-member heterocyclic ring with 1-4 heteroatoms selected from O and N, wherein the said 5- or 6-member heterocyclic ring is optionally substituted with C1-4 alkyl or C(=O)R7; or R5 and R6 together with the carbon atom to which they are attached form =CH2 or 5- or 6-member heterocycloalkyl with 1-4 heteroatoms selected from O and N, wherein the said heterocycloalkyl is optionally substituted with C1-4 alkyl; R7 is hydrogen or C1-4 alkyl; R8 and R9 are, independently of each other, hydrogen or C1-4 alkyl, or R8 and R9 together with the nitrogen atom to which they are attached form a 5- or 6-membered heterocyclic ring with 1-4 heteroatoms selected from O and N. The invention also relates to a pharmaceutical composition, a method for prevention, treatment or alleviation of the severity of conditions accompanied by skin pruritus, application of the said compounds in the manufacture of a medicament for prevention, treatment or alleviation of the said diseases, and to intermediates of general formula wherein R10 is selected from the group consisting of hydrogen and C(O)OR14; R11 is selected from the group consisting of hydrogen and oxo; R12 and R13 are independently selected from the group consisting of hydrogen, C1-C4 alkyl, allyl and C(O)O(C1-C4alkyl); R14 is selected from the group consisting of C1-C4-alkyl; n is 1 or 2.EFFECT: possibility to use the compounds for prevention, treatment or alleviation of conditions accompanied by skin pruritus.27 cl, 3 dwg, 1 tbl, 122 ex
Dimethylamide 7-cyclopentyle-2-(5-piperazin-1-il-pyridine-2-ylamino)-7h-pyrrolo[2,3-d]pyrimidine-6-carbonic acid salt (salts) and method for their production // 2631243
FIELD: pharmacology.SUBSTANCE: invention relates to a new succinate salt of dimethylamide 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid represented by the formula (II) in a hydrated and non-hydrated form. The compound can be used to treat a disease impaired by cyclin-dependent kinases activity inhibition, in particular, CDK1, CDK2, CDK3, CDK4 CDK5, CDK6 and CDK9 kinases. Such a disease can be represented by breast cancer, genitourinary cancer, lung cancer, pancreatic cancer, etc. The succinate salt corresponds to the structural formula given below.EFFECT: increased efficiency of treatment.5 cl, 6 dwg, 2 tbl, 7 ex
ethods for obtaining 5-[2-[7-(trifluoromethyl)-5-[4-(trifluoromethyl)phenyl]pyrazolo[1,5-a]pyrimidine-3-yl]ethinyl]-2-pyridinamine // 2630700
FIELD: pharmacology.SUBSTANCE: invention relates to an improved method for obtaining 5-[2-[7-(trifluoromethyl)-5-[4-(trifluoromethyl)phenyl]pyrazolo[1.5-a]pyrimidine-3-yl]ethinyl]-2-pyridinamine (A), which is useful in treatment of depression and other disorders of the central nervous system. The invention also relates to an improved process for the preparation of formula 9 compound, which is used in the synthesis of compound A as an intermediate. The method for compound 9 preparation comprises the following steps: a) 5-amino-2-iodopyridine 8 reacting with 2-methyl-3-butyn-2-ol by the reaction of Sonogashir in the presence of a PdCl2(PPh3)2CuJ catalyst with triethylamine as a base in 2-methyltetrahydrofuran to obtain compound 13 and b) removing the protecting group in the presence of aqueous sodium hydroxide in toluene as follows: Formula A compound is prepared by compound 3 or 7 reacting with compound 9 obtained above under Sonogashir coupling reaction conditions in an inert solvent. The preferred starting compound 7 is obtained by compound 11 reacting with an iodinating agent, for example, N-iodosuccinimide, under acidic conditions.EFFECT: method allows to obtain compound A in high yield and purity and is suitable for application on a large scale in industrial plants.4 cl, 21 ex
Nitrogen-containing spirocyclic compound and its application in medicine // 2630694
FIELD: pharmacology.SUBSTANCE: compounds can be used to prepare a medicament for treatment or prevention of a disease selected from the group consisting of organ transplant rejection, graft versus host transplantation, autoimmune disease, allergic diseases and chronic myeloproliferative disease. The disease can be selected from rheumatoid arthritis, psoriasis, atopic dermatitis or a disease caused by dry eyes. In the general formula Ra is the same or different and each represents (1) C1-6 alkyl or (2) a halogen atom, n1 is an integer selected from the integers from 0 to 2, Rb are the same or different and each represents (1) C1-6 alkyl or (2) halogen atom, n2 is an integer selected from the integers from 0 to 2, m1 is an integer selected from the integers from 0 to 3, m2 is an integer selected from the integers from 1 to 4, Xa=Xb is (1) CH=CH, (2) N=CH or (3) CH=N, X is (1) a nitrogen atom or (2) C-Rd, where Rd is a hydrogen atom or halogen atom, Rc is a group selected from the following groups (1)-(6): (1) a hydrogen atom, (2) C1-6 alkyl, optionally substituted with 1-5 same or different substituents selected from the following group A, (3) -C(=O)-Rc1, (4) -C(=O)-O-Rc2, (5) -C(=O)-NRc3Rc4, where Rc1, Rc2, Rc3, Rc4 are the same or different and each represents (i) a hydrogen atom or (ii) C1-6 alkyl, optionally substituted with 1-5 same or different substituents selected from the following group A, or (6) a group of the following formula in which Ya is a group selected from the following groups (i) to(iii) (i) C1-6 alkylene, (ii) -C(=O)- or (iii) -S(=O)-O-, ring T is (i) a phenyl, (ii) C3-10 cycloalkyl or (iii) a saturated monoheterocyclyl, which contains 1 nitrogen atom and carbon atoms, and the number of atoms, constituting the ring, is 3-7, Rc5 is the same or different and each represents (i) cyano, or (ii) a nitro group, p is an integer selected from the integers from 0 to 1, group A is a group, consisting of (a) a hydroxyl, (b) C1-6 alkoxy, (c) a cyano, (d) C1-6 alkoxycarbonyl, (e) C1-6 alkylcarboxylic and (f) C2-6 alkenylacyl.EFFECT: increased efficiency of treatment.60 cl, 33 tbl, 8 ex
Compounds // 2630677
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of the general formula ,where Cyc1 is imidazolyl or triazolyl; Cyc2 is phenyl; Cyc3 is phenyl or 5-10 membered heteroaryl containing 1 heteroatom selected from S and N; R1 is halogen; s is equal to 0 or 1, R2 is hydrogen; R3 is hydrogen, C1-8 alkyl or C1-8 alkyl which is substituted by a group selected from pyridyl or -OC1-8 alkyl; Y is N or C (R5); R4 is hydrogen or C1-4 alkyl; R5 is hydrogen or halogen; or R3 and R4 can be taken together to form C2 alkylene; where one carbon of the alkylene chain can be replaced by sulfur; R6 is C1-8 alkyl, Cyc10, halogen or Cyc10 substituted by halogen or cyano, wherein Cyc10 is a 5-membered heteroaryl containing 3-4 nitrogen atoms; m is equal to 2, where each R6 can be the same or different; R7 is halogen, -NH2, -COOR48, -NHC (O) O-C1-8 alkyl, -NHC (O) O-C1-4 alkylene-OC1-8 alkyl; R48 is hydrogen or C1-8 alkyl; n is equal to 1 or 2, where n is an integer 2, each R7 can be the same or different; and R62 is hydrogen, their pharmaceutically acceptable salts or solvates thereof.EFFECT: compounds are factor XIa inhibitors, so they can be used to prevent or treat thromboembolic diseases.15 cl, 3 tbl, 927 ex

Pyperazinyl derivatives for cancer treatment // 2629115
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of the general formula (I), where X represents a (C1-C6)alkyl, phenyl, benzyl, C(O)OR5 or C(O)NHR5 group; R1 represents a hydrogen atom or a C(O)R6 or C(O)OR6 group; R2 represents a hydrogen atom or a (C1-C6)alkyl group; or R2 together with R1 or X form a saturated hydrocarbon chain that forms a 5- or 6-member ring; R3 represents a hydrogen atom or a (C1-C6)alkyl group; R4 represents a halogen atom or a (C1-C6)alkyl, (C1-C6)alkoxy or phenyloxy group, the said group being optionally substituted by one or more halogen atoms; Ar represents a thiophenyl or phenyl group optionally substituted by one halogen atom; and R5 and R6 independently of each other represent a (C1-C6)alkyl, phenyl-(C1-C6)alkyl group or phenyl optionally substituted by one halogen atom. The invention also relates to a pharmaceutical composition and to a process for preparation of general formula (I) compounds.EFFECT: new piperazinyl compounds of the general formula are obtained that can be used for breast cancer, leukemia, colon cancer, pancreatic cancer and ovarian cancer treatment or prevention.12 cl, 1 dwg, 6 tbl, 8 ex
11-(4-tret-butylbenzyl) - and phenacylreplaced 2,3,4,5-tetrahydro [1,3] diazepino [1,2-a] benzimidazole with anxiolytic activity // 2629022
FIELD: pharmacology.SUBSTANCE: invention relates to the new derivatives in the 2,3,4,5-tetrahydro[1,3]diazepino [1,2-a]benzimidazole, with general formula 1: . The new hydrobromides 11-(4-t-butylbenzyl) - and 11-phenacyl substituted 2,3,4,5-tetrahydro[1,3]diazepino[1,2-A]benzimidazoles with anxiolytic activity are obtained.EFFECT: improved compounds properties.4 cl, 2 tbl, 3 ex
Piperazino[1,2-a]indole-1-ones and [1,4] diazeptino[1,2-a]indole-1-one // 2628126
FIELD: medicine.SUBSTANCE: invention relates to application of compounds of general formula I .EFFECT: new compounds, as well as pharmaceutical compositions based thereon, are obtained, that can be used to treat schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorder, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down's syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, and violations resulting from radiation therapy, chronic stress or abuse of neuroactive drugs, such as alcohol, opiates, methamphetamine, phencyclidine or cocaine.11 cl, 1 tbl, 46 ex

9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole and pharmaceutically acceptable salts thereof that express properties of destroyers of transversal cross-links of glycosylated proteins // 2627769
FIELD: pharmacology.SUBSTANCE: invention relates to new 9-benzyl-2-biphenylimidazo[1,2-a]benzimidazole (I) and pharmaceutically acceptable salts thereof.EFFECT: imidazobenzimidazole derivatives having the property of destroyers of transversal cross-links of glycosylated proteins.3 cl, 2 dwg, 1 tbl, 1 ex
Heterocyclyl pyridinylpyrazoles // 2627272
FIELD: chemistry.SUBSTANCE: invention relates to heterocyclylpyridinylpyrazoles of the formula (I), in which R1-R5, X1, U, Q, W, a, b and n have the values defined as defined in the invention formula and their agrochemically active salts. Compounds of formula (I) can be used to control phytopathogenic harmful fungi in agriculture, horticulture, forestry, livestock, materials protection, household and hygiene, and to reduce the content of mycotoxins in plants and parts of plants. The invention also relates to the use of compounds of formula (I) and to method and composition for controlling phytopathogenic harmful fungi in and/or on plants or in and/or on plant seeds.EFFECT: decrease the content of mycotoxins in plants and parts of plants.10 cl, 7 tbl, 31 cl

Tricyclic inhibitors of gyrase // 2626979
FIELD: pharmacology.SUBSTANCE: invention relates to new tricyclic compounds of formula I having an activity of inhibitors of gyrase B (GyrB) and topoisomerase IV (ParE) enzyme. The compounds may find application in bacterial infections treatment. The invention also relates to a method for preparation of compounds of formula I and formula (1) intermediates for their preparation. In formula I: . L is O or S; R8 is H, Cl, F, Br, OH, NH2, C1-3alkyl, amino-C1-3alkyl, aminocyclopropyl, OCH3, OCH2CH3, cyclopropyl, CH2cyclopropyl, CH2Cl, CHCl2, CCl3, CH2CH2Cl, CH2Br, CHBr2, CH2F, CHF2, CF3, CH2CH2F, CH2CHF2, CH2CF3, NHNH2, NHOH, NHNHCH3, NHOCH3, NHCD3, SCH3 or NHCOH; X, Y and Z are independently selected from the group consisting of N, CRX, CRY and CRZ, provided that no more than two of X, Y and Z are N. At that, RX is H, CH3, Cl, Br or F. At that, RY is H, CH3, CHF2, CF3, CN, CH2CH3, Cl, Br or F. At that, RZ is H, CH3, Cl, Br or F; R2 is a 6-membered monocyclic aryl or 6-membered mono- or 9-10 membered bicyclic heteroaryl ring, wherein the heteroaryl ring contains 1 to 3 heteroatoms selected from O, S and N. The said 6-membered monocyclic aryl ring, 6- Membered monocyclic heteroaryl ring and a 9-10 membered bicyclic heteroaryl ring may be optionally substituted with 0-3 substituents selected from OH, CO2H, CO2CH3, C(O)NH2, C(O)CH3, =O, CN, NH2, Br, Cl, F, SO3H, SO2NH2, SO2CH3, SOCH3, NHOH, C(O)NHOCH3, CH(OH)CH3, C(OH)(CH3)2, SCH3, or C1-C6alkyl or C3-C6cycloalkyl having 0-2 heteroatoms selected from O, S or N, optionally substituted with C1-C4alkyl, OH, CN, =O, NH2, Br, F, Cl. The bicyclic heteroaryl ring can be spiro-fused with cyclopropyl; or R2 is or ; R4 is: H; optionally substituted with ORa, where Ra is pyridyl, pyrimidinyl, optionally substituted with CH3 and NH2; optionally substituted saturated secondary or tertiary amine selected from a 4-6 membered aliphatic amine, a 4-6 membered monocyclic amine, a 5-10 membered bicyclic amine with 1 to 3 heteroatoms selected from N, O or S. The said optionally substituted saturated 5-10 membered bicyclic amine may be a spiro- or orthocondensed bicyclic amine, or optionally substituted 5-6-membered unsaturated cyclic residue containing 0-2 N heteroatoms. The optionally substituted saturated secondary or tertiary amine is attached to ring C via N of the secondary or tertiary amine, and the optional substituent is selected from OH, halogen, NH2, C(O)CH2NH2, C(O)NH2, CH2NHC(O), C5-6heterocyclyl, optionally substituted with CH3 and CF3, CH2OH, -C3-6cycloalkyl, optionally substituted with NH2, -C3-6heterocyclyl containing 0-2 N atoms, optionally substituted with NH2, -CH3, -C(O)CH3, -C(O)C3-6heterocyclyl containing 1 to 3 O atoms, -CH(OH)C3-6heterocyclyl containing 1 to 3 S atoms, -NHCOCH3, -NHCH2CH2CN, -NHCH2C3-6cycloalkyl, -C1-4alkylC3-6heterocyclyl containing 0-2 heteroatoms selected from O and N, -C1-4alkylNH2, =NOCH3, -NHC(O)CH2NH2, -NHCH2CH2OH, -NHCH2CH2NH2, -NHC(O)CH(NH2)CH2OH, -NHC(O)CH2NHC(O)CH(NH2)CH2OH, -C(O)OCH2CH3, -OC1-4alkyl. In the intermediates of formula (1), G1 and G2 are leaving groups independently selected from the group consisting of SH, OH, Cl, Br, F, I, SR, SOR, SO2R, OSO2 R and OBt; R is C1-8alkyl, Ar, wherein Ar is phenyl, optionally substituted with C1-4alkyl, C1-4alkoxy, halogen or NO2; Bt is benzotriazole; R8 is H, Cl, F, Br, OH, NH2, C1-3alkyl, amino-C1-3alkyl, aminocyclopropyl, OCH3, OCH2CH3, cyclopropyl, CH2cyclopropyl, CH2Cl, CHCl2,CCl3, CH2CH2Cl, CH2Br, CHBr2, CH2F, CHF2, CF3, CH2CH2F, CH2CHF2,CH2CF3, NHNH2, NHOH, NHNHCH3, NHOCH3, NHCD3, SCH3 or NHCOH; and X, Y and Z are independently selected from the group consisting of N, CRX, CRY and CRZ respectively, provided that no more than two of X, Y and Z are N.EFFECT: improved compounds properties.35 cl, 3 dwg, 11 tbl, 7 ex
2-amino-substituted 6-methoxy-4-trifluoromethyl-9h-pyrimido[4,5b]indoles, method for their production, application and prediminaries // 2625316
FIELD: pharmacology.SUBSTANCE: invention relates to new 2-amino-substituted 6-methoxy-4-trifluoromethyl-9H-pyrimido[4,5-b]indoles of general formula I and their pharmaceutically acceptable salts, as well as to the new compounds of formula (II), preceding the compounds of formula (I). The compounds of formula I possess anti-tumor activity and are useful in the therapy of myelogenous leukemia and colon cancer. In the formula (I), R=C1-C6-alkyl; C1-C3-alkyl-O-CH2CH2-; R1C6H4CH2-, where R1=H, Me, MeO; , where R2=H or Me. In the formula (II), X means S (IIa), SO2 (IIb). The method for preparation of formula (I) compounds comprises intramolecular cyclization of N-(5-iodo-2-methylthio-6-trifluoromethylpyrimidin-4-yl)-N-methyl-N-(4-methoxyphenyl) amine to form 9-methyl-2-methylthio-6-methoxy-4-trifluoromethyl-9H-pyrimido[4,5-b]indole, at heating in the presence of a base and a catalyst, subsequent oxidation and nucleophilic substitution of the 2-methylsulfonyl group in the resulting product with the corresponding primary amine.EFFECT: increased activity of the composition.11 cl, 1 tbl, 8 ex
8-carbamoyl-2-(2,3-di-substituted pyrid-6-yl)-1,2,3,4-tetrahydroisoquinoline derivatives as apoptosis-inducing agents for cancer treatment // 2625315
FIELD: pharmacology.SUBSTANCE: invention relates to organic chemistry, namely a heterocyclic compound of formula (I) or to a therapeutically acceptable salt thereof, where X is benzo[d]thiazolyl, thiazolo[5,4-b]pyridinyl, thiazolo[4,5-c]pyridinyl, imidazo[1,2-a]pyridinyl, thiazolo[5,4-c]pyridinyl, thiazolo[4,5-b]pyridinyl, imidazo[1,2-a]pyrazinyl or imidazo[ 1,2-b]pyridazinyl; Y1 means pyrrolyl, pyrazolyl, triazolyl or pyridinyl; where Y1 is optionally substituted with 1 or 2 substituents independently selected from R5, CN and Cl; L1 is selected from (CR6R7)q, (CR6R7)s-O-(CR6R7)r, (CR6R7)s-S-(CR6R7)r, (CR6R7)s-S(O)2-(CR6R7)r and (CR6R7)s-NR6A-(CR6R7)r; Y2 means mono- or tricyclic C8-C10-cycloalkyl, spiro[2.5]octyl, spiro[3.5]nonyl, oxatricyclo[3.3.1.13,7]decyl or azabicyclo[3.2.1]octyl; where Y2 is optionally substituted with 1, 2 or 3 substituents independently selected from R8, OR8, SO2R8, CO(O)R8, OH and Br; Z1 is selected from , R1 and R3 are absent; R2 is deuterium or C1-C6-alkyl; R5 is C1-C6-alkyl; R6A is selected from hydrogen and C1-C6-alkyl; each R6 and R7 are hydrogen; R8 is selected from the group consisting of C1-C3-alkyl, morpholinyl and dioxydothiomorpholinyl; where R8, meaning C1-C6-alkyl, is optionally substituted with a substituent selected from R16, OR16, SO2R16 and NHR16; Rk is selected from C1-C6-alkyl, morpholinyl, cyclopropyl and C1-haloalkyl; R16 Is selected from C1-C4-alkyl, phenyl, morpholinyl and tetrahydropyranyl; where R16, meaning C1-C4-alkyl, is optionally substituted with 1 substituent selected from OCH3, OCH2CH2OCH3 and OCH2CH2NHCH3; q is 1 or 2; s, m and p is 0; r is 0 or 1; N is 0, 1, or 2. The invention also relates to specific compounds, pharmaceutical compositions based on these compounds and a method for treatment of these diseases.EFFECT: new heterocyclic compounds are obtained, that are useful for treatment of some cancers.16 cl, 3 tbl, 86 ex

Pyrazole derivatives applied as protein kinase inhibitors // 2623221
FIELD: chemistry.SUBSTANCE: invention relates to compounds selected from the following compounds 73 and 75, and their pharmaceutically acceptable salts, which can find application in the treatment of cancer or leukemia. The invention also relates to pharmaceutical compositions comprising said compounds, use of said compounds for the manufacture of a medicament for the treatment of cancer or leukemia, and a method of treatment of these diseases. Compound 73, structure 2-(2.2-dioxo-2.3-dihydro-1H-2lyamda*6*-benzo[c]thiophen-5-ylamino)-9-(2-ftorfinil)-5metil-5,7,8,9-tetragidropiramido[4.5-b][1.4]diazepin-6-one; Compound 75, structure 2-(2.2-dioxo-2.3-dihydro-1H-2lyamda*6*-benzo[c]thiophen-5-ylamino)-5-methyl-phenyl-5,7,8,9-etrahydropyrimido[4.5-b][1.4]diazepine-6.EFFECT: high effectiveness of compounds.7 cl, 3 dwg, tbl 8, 9 ex
Tetrahydrotriazolopyrimidine derivatives as inhibitors of human neutrophil elastase // 2622643
FIELD: pharmacology.SUBSTANCE: invention compounds have the properties of human neutrophil elastase (HNE) inhibitors. In formula I A represents CH; R1 is selected from hydrogen; a (C1-C6) alkyl; a (C1-C6)alkylNR7R8group; a (C1-C4)alkenyl; a (C1-C6)alkylphenyl, where the phenyl ring is possibly substituted by a (C1-C6)alkylNR15R16 group or a (C1-C6)alkylN+R15R16R17group; a -(CH2)nCONR5R6group; a -CH2-(CH2)nNR5SO2R6group; a -(CH2)t-(C6H4)-SO2(C1-C4)alkyl group; a -(CH2)rSO2(C1-C4)alkyl group, wherein such (C1-C4)alkyl is possibly substituted by a -N+R15R16R17group; a -SO2-phenyl group. Such phenyl ring is possibly substituted by a (C1-C6)alkylNR7R8group; and a -(CH2)n-W group, where W represents a 6-membered heteroaryl ring with one heteroatom N, which is possibly substituted by a group -SO2(C1-C4)alkyl; n means 1; t means zero, 1; r means 2, 3; R5 is selected from the group consisting of hydrogen, a (C1-C6)alkyl, a (C1-C6)alkylNR16R15group and a (C1-C6)alkylN+R17R15R16group; R6 represents hydrogen or a (C1-C6)alkyl; R7 is selected from the group consisting of a (C1-C6)alkyl, a carbonyl(C1-C6)alkyl group, a -SO2(C1-C4)alkyl group and a (C1-C6)alkylNR16R15group; R8 represents a (C1-C6 )alkyl; alternatively, R7 and R8 can form, together with the nitrogen atom to which they are attached, a (C5-C7)heterocycloalkyl ring system, which is possibly substituted by oxo; R16 represents a (C1-C6)alkyl; R15 represents a (C1-C6)alkyl; R17 represents a (C1-C6)alkyl; R2 represents hydrogen or -SO2R4, where R4 is selected from a (C1-C6)alkyl; R14 represents a cyano group or a -C(O)-XR3group; X is a divalent group selected from -O- and -NH-; R3 represents a group selected from hydrogen; a (C1-C6)alkyl; a group of formula -[Alk1]-Z, where Alk1 represents a (C1-C4)alkylene radical, and Z represents NR9R10, where R9 and R10 independently represent a (C1-C6)alkyl. The invention also relates to pharmaceutical compositions and to a method of treating a disease or a condition in which HNE is involved.EFFECT: new formula compounds obtained, having the properties of human neutrophil elastase inhibitors.16 cl, 1 tbl, 39 ex

Compound 8-fluorophthalazine-1(2h)-one as inhibitors of bruton tyrosine kinase // 2622391
FIELD: pharmacology.SUBSTANCE: compounds of 8-fluorophthalazine-1(2H)-ones of formula II are proposed, wherein one of X1, X2 and X3 represent N, and the other symbols have meanings defined in claim 1 of the invention formula, or stereoisomers, gautomers and pharmaceutically acceptable salts thereof. The compounds proposed inhibit the kinase Btk (Bruton tyrosine kinase) and can be used to treat immune disorders, such as inflammation, mediated by kinase Btk.EFFECT: increased efficiency while using the compounds of formula II for the diagnosis and treatment in vitro, in situ and in vivo such disorders in mammalian cells, or associated pathological conditions.25 cl, 8 dwg, 2 tbl, 69 ex

ethods of producing conjugates // 2621035
FIELD: chemistry.SUBSTANCE: invention relates to a process for preparing a conjugate comprising an agent that binds to cells (CBA) and conjugated to a cytotoxic compound by a binding group, where the said process comprises reacting of the modified cytotoxic compound with modified CBA at pH from about 4 to about 9, wherein the modified CBA includes a residue of a bifunctional crosslinking agent associated with CBA and the said residue includes a binding group and a group capable of reacting with a thiol, wherein CBA is an antibody and the modified CBA is represented by the formulas set forth in the claims, the modified cytotoxic compound comprises a thiol group and is obtained by reacting of imine-containing cytotoxic compound (carrying a thiol group) with a reagent capable of reacting with imines, and wherein the imine-containing cytotoxic compound is represented by the formula: , wherein X' is -H, Y' is -H or oxo-group, W' represents -N(Re)-, Re is -(CH2-CH2-O)n-Rk, wherein Rk is -H, a linear, branched or cyclic alkyl having from 1 to 6 carbon atoms, n is an integer from 1 to 24, Rx is a linear or branched alkyl having from 1 to 6 carbon atoms, A and A' are-O-, R6 is -OR, R, in each case, is a linear or branched alkyl having from 1 to 6 carbon atoms, G is a -CH-, and the reagent capable of reacting with imines is selected from the group consisting of sulfite, metabisulfite and dithionite. The invention also relates to other methods of producing conjugate.EFFECT: herein there is a description of new methods of obtaining a conjugate using a reagent capable of reacting and imines for modifying the imine-containing cytotoxic compounds.54 cl, 28 dwg, 16 tbl, 16 ex
2-furyl-6-nitro-1,2,4-triazolo [1,5-a] pyrimidine-7-one // 2620594
FIELD: pharmacology.SUBSTANCE: invention relates to 2-furyl-6-nitro-1,2,4-triazolo[1,5-a] pyrimidin-7-one. 1.EFFECT: new compound is obtained which may be used for sepsis treatment.1 tbl, 1 ex
Derivatives of 1,2,4-triazolo [1,5-c]pyrimidine-2-sulfonamide that have a herbicidal activity // 2619467
FIELD: chemistry.SUBSTANCE: invention relates to 1,2,4-triazolo[1,5-c]pyrimidine-2-sulfonamide derivatives of the general formula , in which if R1 - H, then R2 - H if R1 - F, then R2 - F, which has herbicidal activity.EFFECT: new compounds, which have herbicidal activity, were obtained.3 tbl, 3 ex
Bruton's tyrosine kinase inhibitors // 2619465
FIELD: pharmacology.SUBSTANCE: compounds can be used as therapeutically active substances for the treatment of inflammatory and/or autoimmune conditions selected from rheumatoid arthritis and asthma. In formula I A is phenyl, n is 1 or 2, R1 is CH2NHC(=O)R1' or CH2NHC(=O)CH2NHR1', where n is 1. And one R1 is halogen, and the other R1 represents CH2NHC(=O)R1' or CH2N(CH3)C(=O)R1', when n is 2. R1' represents a lower alkoxy group, phenyl, an unsaturated or partially unsaturated 8-9-membered bicyclic heterocycle containing 1-2 heteroatoms in the bicyclic system selected from nitrogen and sulfur, or a 4-6-membered monocyclic heteroaryl with 1-3 heteroatoms selected from nitrogen, oxygen and sulfur, or a 4-5-membered heterocycloalkyl containing oxygen or nitrogen atoms as heteroatoms, optionally substituted by one or more R1". Each radical R1" is an independent lower alkyl, halogen, 3-6-membered cycloalkyl, 4-membered heterocycloalkyl with an oxygen atom as a heteroatom, lower alkyl-4-membered heterocycloalkyl with an oxygen atom as a heteroatom, oxo group, cyano-lower alkyl, hydroxyl-lower alkyl or lower alkoxy group. R2 is H, R3 or R4. R3 represents C(=O)OR3', C(=O)R3' or C(=O)NH(CH2)2R3'. R3' is H, a lower alkyl, 6-membered heterocycloalkyl with 1-2 heteroatoms selected from nitrogen and oxygen, an amino group or OH. R4' is a pyrasolyl possibly substituted with R4'. And R4' is a methyl, CH2-CH2N(CH3)2, CH2C(=O)OCH2CH3, CH2C(=O)OH or CH2CH2OH.EFFECT: increased efficiency of treatment.18 cl, 2 tbl, 51 ex

Derivatives of pyrrolopyrimidine useful as jak-kinases inhibitors // 2618673
FIELD: chemistry.SUBSTANCE: invention relates to a heterocyclic compound of the formula (I) or to its enantiomer, a diastereomer and a mixture thereof and a pharmaceutically acceptable salt thereof, wherein A: CH or N; L: bond or C1-2alkyl; R1 is selected from hydrogen, C1-4alkyl, heteroaryl, - (CH2)nC(O)OR15, -C(O)R15, -C(O)NR16R17, and -S(O)mR15, where each of alkyl or heteroaryl is possible is substituted with 1-3 groups selected from halogen, hydroxy, cyano, C1-2alkyl, C1-2alkoxy, C3cycloalkyl, C6aryl, pyridine and - (CH2)nC(O)OR15; R2 or R4 is independently selected from hydrogen and C1-2alkyl; R or R3 is independently selected from hydrogen and halogen; R5 or R6 is independently selected from hydrogen and C1-2alkyl; R7, R8, R9 or R10 is independently selected from hydrogen, C1-2alkyl and hydroxyC1-2alkyl; R11, R12, R13 or R14 is independently selected from hydrogen or R11 and R12 or R13 and R14 taken together form an oxo group; R15 is selected from C1-4alkyl, C3cycloalkyl, C2alkenyl, C6aryl and pyridine, wherein each of alkyl, cycloalkyl or heteroaryl is optionally substituted with 1 to 4 groups selected from halogen, hydroxy, cyano, C1-4alkoxy, C6aryl, tetrazole, -NR19R20, -S(O)mR18, -NHC(O)OR18 and -NHS(O)mR18; R16 or R17 is independently selected from hydrogen, C1-3alkyl and heteroaryl, wherein heteroaryl is optionally substituted by one selected from C1-2alkyl, hydroxy, C1-2alkoxy, C3cycloalkyl, hydroxyC1alkyl and-OR18; R18 is selected from C1-4alkyl and hydroxyC1-4alkyl; R19 or R20 is independently selected from the group consisting of hydrogen; M is 0, 1 or 2; N is 0 or 1; P is 0, 1 or 2; Q is 0 or 1; S is 1 or 2; And t is 1 or 2. The invention also relates to particular intermediates, a process for the preparation of a compound of formula (I), a pharmaceutical composition based on it, the use of a compound of formula (I), a method for inhibiting JAK kinases, and a method for treating certain diseases of the immune system.EFFECT: new heterocyclic compounds possessing the activity of JAK-kinase inhibitor have been obtained.22 cl, 7 tbl, 158 ex

N-piperidin-3-yl-benzamide derivatives for cardiovascular diseases treatment // 2618628
FIELD: pharmacology.SUBSTANCE: invention relates to substituted amide compounds of formula pharmaceutical compositions containing such compounds and application of such compounds for lowering plasma lipid levels, such as low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides, and thus, for treatment of diseases exacerbated by high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in mammals, including humans.EFFECT: increased efficiency of compounds application.42 cl, 10 dwg, 55 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

Pyridone and aza-pyridone compounds and methods of use // 2617405
FIELD: chemistry.SUBSTANCE: invention relates to a compound selected from formula I, or its stereoisomers, or pharmaceutically acceptable salts thereof, where R1 is optionally substituted C1-C3 alkyl; R2, R3 and R4 are independently selected from H, F, Cl; R5 is selected from (i) optionally substituted C6-C20 aryl, selected from phenyl; (ii) optionally substituted C5-C20 heteroaryl, selected from pyrazolyl, pyridinyl, pyrimidinyl, tetrahydroisoquinolinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazinyl, 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazinyl, 4,6,7-trihydropyrazolo[3,2-c][1,4]oxazinyl, 5,6,7,8-tetrahydro-1,6-naphthyridinyl, 2,3-dihydro-1H-isoindolyl, 4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinyl; (iii) optionally substituted -(C6-C20 aryl)-(C3-C20 heterocyclyl), where heterocyclyl is selected from azetidinyl, piperidinyl, morpholino, piperazinyl; (iv) optionally substituted -(C5-C20 heteroaryl)-(C3-C20 heterocyclyl), where heteroaryl is selected from pyridinyl and pyridazinyl and heterocyclyl is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, 1,4-diazepanyl, 2,6-diazaspiro[3.3]heptanyl, 7,9-diazabicyclo[3.3.1]nonanyl, hexahydropyrrolo[3,4-c]pyrrolyl, morpholino; (v) optionally substituted -(C5-C20 heteroaryl)-(C1-C6 alkyl), where heteroaryl is selected from pirazolyl and pyridinyl; or (vi) optionally substituted -(C5-C20 heteroaryl)-C(=O)-(C3-C20 heterocyclyl), selected from (pyridinyl)-C(=O)-(morpholino); R6 represents H or C1-C3 alkyl; Y1 and Y2 are independently selected from CR6 and N; where C1-C3 alkyl, C3-C20 heterocyclyl, C6-C20 aryl and C5-C20 heteroaryl optionally substituted with one to three groups, independently selected from D, F, Cl, Br, I, -CH3, -CH2CH3, -CH2CH(CH3)2, -CH2OH, -CH2CH2OH, -C(CH3)2OH, -CH2F, -OC(O)CH3, -COCH3, -NHCH3, -N(CH3)2, =O, -OH, -OCH3, -OCH2CH2N(CH3)2, -OP(O)(OH)2, -CH2OCH3, cyclopropyl, azetidinyl, 1-(methylazetidin-3-yl)oxy, N-methyl-N-oxetan-3-ylamino, azetidin-1-ylmethyl, oxetanyl and morpholino; where group (a), formed Z1, Z2, Z3, Z4, Z5, X and NC(O), forms structure, given in claim, and wherein wavy line indicates bonding point. Invention relates to a pharmaceutical composition for treating a condition, mediated by Bruton's tyrosine kinase, containing a compound of formula (I) and a pharmaceutically acceptable carrier, lubricant, a diluent or filler. Compounds of formula (I) are intended for use as a drug for treating cancer, mediated by Bruton's tyrosine kinase.EFFECT: pyridone and aza-pyridone compounds for treating disorders mediated by Bruton's tyrosine kinase (Btk).20 cl, 9 dwg, 4 tbl, 907 ex (а)
Geterocyclilpyridinylpyrazols as fungicidal agents // 2616293
FIELD: chemistry.SUBSTANCE: in formula (I) R1-R5, X1, U, Q, W, Y, n, a, b have the values defined in the invention formula. The invention also relates to the composition based on compounds of formula (I) for controlling phytopathogenic harmful and mycotoxin-producing fungi, the process for its preparation and the method of control of the mentioned fungi. Furthermore, the invention relates to the use of compounds of formula (I) for controlling phytopathogenic harmful fungi in plants and / or plants or the seeds and / or plant seeds, and for reducing the amount of mycotoxins in plants and parts of plants and to the use of compounds of formula (I) for the treatment of transgenic plants.EFFECT: invention provides for controlling with phytopathogenic harmful and mycotoxin-producing fungi.9 cl, 7 tbl, 162 ex
Azetidine compounds, compositions and their use as inhibitors of soluble epoxide hydrolase // 2615995
FIELD: chemistry.SUBSTANCE: invention refers to new azetidine derivatives, having soluble epoxide hydrolase (sHE) inhibitor activity. Disclosed are compounds of formula I: R1-L1-A-L2-R2, their stereoisomers and pharmaceutically acceptable salts, where A is selected from a group, consisting of Ia, Ib or Ic, X is N or CH2, Y is N, CH2, CH, L1 is a bond, -C(O)-, -SO2- or -(CH2)0-3-NR3-C(O)-; L2 is a bond, -(CH2)1-3-, -NH-C(O)-NH-, -C(O)-, -SO2- or -(CH2)0-3- NR3-C(O)-; R1 is phenyl, where phenyl is unsubstituted or substituted with one or two R5, 6-member heteroaryl with two nitrogen atoms in ring, where rest of ring atoms are carbon atoms, or adamantyl; R2 is phenyl, -(CH2)1-3-phenyl, where phenyl is unsubstituted or substituted with one or two R5, or 6-member heteroaryl with two nitrogen atoms in ring, where rest of ring atoms are carbon atoms; R3 is hydrogen atom; R4 is a hydrogen atom; R5 is a halogen atom, C1-C6-haloalkyl, C1-C6-haloalkoxy or -C(O)OR4.EFFECT: novel chemical compounds.13 cl, 1 tbl, 21 ex Ia, Ib, Ic

Heterocyclic compounds useful as pdk1 inhibitors // 2615130
FIELD: chemistry.SUBSTANCE: present invention relates to novel compounds of general formulae II, III, IV and V, where values of radicals are given in description, or pharmaceutically acceptable salts thereof, which can be used as PDK1 inhibitors.EFFECT: present invention also relates to pharmaceutical compositions based thereon and to methods of treating cancer, mediated by protein kinase PDK1.32 cl, 2 tbl, 445 ex
ethod of producing 2-substituted 1-hydroxypyrrolo[3,4-ƒ]indole-5,7-(1h,6h)-diones // 2613582
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing 2-substituted 1-hydroxypyrrolo[3,4-ƒ]indole-5,7(1H,6H)-diones, where R=C6H5 or 4-CH3C6H4, or 4-OCH3C6H4, or 2-thienyl, which can be used as precursors for synthesis of biologically active substances, medicinal preparations, hexazocyclanes. Method of producing 2-substituted 1-hydroxypyrrolo[3,4-ƒ]indole-5,7(1H,6H)-diones includes two steps. At first step substituted 4-nitro-5-(2-oxoethyl)phthalonitriles are heated in a medium of polyphosphoric acid with density to form corresponding substituted 5-nitro-6-(2-oxoethyl-1H-isoindole-1,3(2H)-diones. At second step substituted 5-nitro-6-(2-oxoethyl)-1H-isoindole-1,3(2H)-diones are reduced with tin dichloride to obtain desired 2-substituted 1-hydroxypyrrolo[3,4-ƒ]indole-5,7(1H,6H)-diones.EFFECT: use of disclosed method for synthesis of 2-substituted 1-hydroxypyrrolo[3,4-ƒ]indole-5,7(1H,6H)-diones enables to obtain novel, previously not described in literature indoles with an imide fragment.1 cl, 4 ex
Ido inhibitors // 2613579
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, in particular, to derivatives of imidazo[5,1-a]isoindole of structure given below, or to a stereoisomer or pharmaceutically acceptable salt thereof, where bond α is a single or double bond; n = 0 or 1; R1: halogen or -OR; R2: -C1-4alkyl-RA or -C2-4alkenyl-R3, if bond α is a single bond; and R2: =C(H)RA, if bond α is a double bond; in which RA: -CN, -C(O)R3, -C(O)OR3, -C(O)N(R3)(RC), -C(ORB)(R3)(RC), -C(NHRB)(R3)(RC), or -C(=N-ORC)R3, where RB: hydrogen, -C(O)R3, -C(O)N(H)R3, -C(O)(CH2)2COOR, -C(O)(CH2)1-4(NR)COOR, -C(O)CH(NH2)(RD), or -P(O)(OR3)2; where RD: methyl or -CH(CH3)2; R3: hydrogen, C1-6alkyl, phenyl, imidazolyl, furanyl, thiazolyl, pyridinyl, C5-6cycloalkyl, C3-8cycloalkenyl, piperidinyl, pyrrolidinyl, tetrahydropyranyl, azetidinyl or C6cycloalkylC1alkyl-, where each alkyl, cycloalkyl, piperidinyl, pyrrolidinyl, tetrahydropyranyl and azetidinyl is optionally and independently substituted with one group =R32 and optionally and independently substituted with one or two groups R31; each phenyl, imidazolyl, furanyl, thiazolyl and pyridinyl is optionally substituted with one or two groups R31; where R31: halogen, nitro, C1-6alkyl, -C1-6alkyl-R33, C1-6haloalkyl, -OR, -N(R)2, -C(O)OR, -C(O)N(R)2, -C(O)R, -S(O)2R, -OC(O)R, -N(R)C(O)R or -N(R)C(O)OR, where R33: -OR; R32: =O, =C(R34)2, =(spiro-C3-8cycloalkyl), or =(spirodioxalanyl), where R34: hydrogen, halogen, C1-6alkyl or -C1alkyl-OR; RC: hydrogen or C1-6alkyl; and R: hydrogen or R10, where R10: C1-6alkyl, phenyl, thiophenyl, C5-6cycloalkyl, pyrrolidinyl, tetrahydropyranyl, phenylC1-6alkyl, heteroarylC1-2alkyl- (where heteroaryl group is a pyridine, pyrimidine or imidazole) or tetrahydropyranC1alkyl, where each of alkyl, phenyl, cycloalkyl and phenylC1-2alkyl optionally substituted with one or two groups, which independently represent a halogen, C1-6alkyl, C1haloalkyl, -OR11, -N(R11)2 or -N(R11)S(O)2R11, where R11: hydrogen or C1-6alkyl. Invention also relates to specific compounds, pharmaceutical composition based on declared imidazo[5,1-a]isoindole and a method of treating indoleamine-2,3-dioxygenase (IDO) mediated immunosuppression.EFFECT: novel derivatives of imidazo[5,1-a]isoindole are obtained, having useful biological properties.42 cl, 1 dwg, 75 ex
2-pyridyl substituted imidazoles as alk5 and/or alk4 inhibitors // 2612958
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to a novel 2-pyridyl-substituted imidazole derivative of formula (I), where R1 is phenyl, pyridyl or thienyl, condensed with a structural fragment, which together with two ring members of said phenyl, pyridyl or thienyl forms a 5-6-member aromatic or non-aromatic saturated ring, wherein said ring optionally contains up to two heteroatoms, independently selected from O, N and S, and condensed phenyl ring is optionally substituted with one group, independently selected from halogen, -O-C-1-6alkyl, -C1-6alkyl, -O-(CH2)q-NR4R5, or 5-member heteroaryl containing up to two heteroatoms, independently selected from N; or R1 is phenyl, substituted with one or more groups, independently selected from halogen, -O-C1-6alkyl, -S-C1-6alkyl, -C1-6alkyl, -C1haloalkyl, -CN, -(CH2)p-NR4R5, -(CH2)p-NHCOR4, -(CH2)p-NHCO2R4; -(CH2)p-NHSO2R4 or N-bound 6-member heterocycle, where said heterocycle comprises two heteroatoms, independently selected from O, N, and optionally substituted with C1-6alkyl; R2 is -C1-6alkyl; R3 is H, -(CH2)p-NR4R5, -(CH2)p-CN, -(CH2)p-CO2R4, -(CH2)p-CONR4R5, -(CH2)p-OR4, -(CH2)p-NHCOR4; R4 and R5 independently denote H or -C1-6alkyl; p denotes an integer ranging from 0 to 1; q denotes 2; n denotes an integer ranging from 1 to 2; X is NR7; and R7 is H or -CO-C1-6alkyl. Invention also relates to use of a compound of formula (I), a pharmaceutical composition based on compound of formula (I) and to a method of preventing or treating diseases, based on use of compound of formula (I).EFFECT: technical result is obtaining novel heterocyclic compounds effective in treating or preventing a disease, mediated by ALK5 and/or ALK4 receptors in a mammal.8 cl, 44 ex, 1 tbl
Sodium salt of diethyl ether of 4-oxo-1,4-dihydropyrazolo[5,1-c]-1,2,4-triazine-3,8-dicarboxylic acid monohydrate // 2612300
FIELD: chemistry.SUBSTANCE: invention relates to a sodium salt of diethyl ether of 4-oxo-1,4-dihydropyrazolo-[5,1-c]-1,2,4-triazine-3,8-dicarboxylic acid monohydrate, having antiglycating activity .EFFECT: technical result is obtaining a novel compound, having antiglycating activity, which can be used for treating and preventing diabetes consequences.1 cl, 3 tbl, 3 ex
 
2550940.
Up!