(A61K31/519)

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
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

Combination treatment of cancer // 2640485
FIELD: pharmacology.SUBSTANCE: proposed: a combination for application as a drug for cancer treatment, containing: (S)-4-amino-N-(1-(4-chlorophenyl)-3-hydroxypropyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363) or a salt thereof with an androgen receptor signal modulator selected from 4-{3-[4-cyano-3-(trifluoromethyl)-phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl}-2-fluoro-N-methylbenzamide (MDV-3100) and N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)-sulfonyl]-2-hydroxy-2-methylpropanamide (bicalutamide) or a salt thereof, a set of these components for application in cancer treatment (versions).EFFECT: greater inhibition of tumour growth by combining the said compound against monotherapy of castration-resistant prostate cancer, the combination showed good tolerability.9 cl, 3 dwg, 1 tbl
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
ethod for adjuvant therapy of cancer // 2640180
FIELD: medicine.SUBSTANCE: methods of the invention include administration of therapeutically effective doses of dabrafenib and trametinib. The composition of the invention comprises a combination of dabrafenib and trametinib.EFFECT: application of inventions allows to improve disease-free survival in patients with melanoma.8 cl, 1 tbl
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
Compounds of thienopyrimidine // 2637925
FIELD: pharmacology.SUBSTANCE: invention relates to a compound of formula I: , where group A is independently monocyclic or bicyclic aryl or heteroaryl optionally substituted by one or more A'; each group A' is independently C1-6 alkyl, halogen, cyano or heteroaryl; group R1 is tetrahydropyranyl substituted with an amino group; or pharmaceutically acceptable salts thereof, which are SYK inhibitors and are useful for treatment of autoimmune and inflammatory diseases.EFFECT: increased efficiency of treatment.10 cl, 2 tbl, 25 ex
ethod for producing tienopyrimidine compounds // 2637309
FIELD: chemistry.SUBSTANCE: invention relates to the method for producing (S)-1-(4-((2-(2-aminopyrimidine-5-yl)-7-methyl-4-morpholinotino[3,2-d]pyrimidine-6-yl)methyl)piperazine-1-yl)-2-hydroxypropan-1-ona having the structure: , and also to the new intermediate oxalate (S) -2-hydroxy-1-(piperazine-1-yl)propan-1-ona having the following structure: A new method for producing (S)-1-(4-((2-(2-aminopyrimidine-5-yl)-7-methyl-4-morpholinotino[3,2-d]pyrimidine-6-yl)methyl)piperazine-1-yl)-2-hydroxypropan-1-ona, which is a double inhibitor of mTOR/PI3K GDC-0980.EFFECT: new method of producing connections.16cl, 1 tbl, 18 ex
Stabilized pemetrexede composition // 2636783
FIELD: pharmacology.SUBSTANCE: invention refers to cancer pemetrexed compositions in an airtight container that contains pemetrexed or its pharmaceutically acceptable salt, as the active ingredient, as well as N-acetyl-L-cysteine and sodium citrate, where this the composition has gaseous oxygen content of 3% vol./vol. in the container free space or less relative to the total amount of free space.EFFECT: invention implementation allows to obtain a stable pemetrexed composition.7 cl, 14 tbl, 39 ex, 1 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

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
New tetrahydropyrimidine connection or its salt // 2636310
FIELD: pharmacology.SUBSTANCE: invention relates to a new tetrahydropyridopyrimidine compound of the general formula (I) or a pharmaceutically acceptable salt thereof. The compounds possess an inhibitory activity against the androgen receptor (AR) and can be used to treat a tumour associated with activity (AR). In the general formula ,X is a halogen atom or halogen-C1-3an alkyl group; R is a phenyl group which is substituted by R1 and can also be substituted by R2, or a 5- or 6-membered heteroaryl group which contains 1 to 3 heteroatoms selected from a nitrogen, oxygen or sulfur atom and which is substituted by R1 and can also be substituted by R2; R1 represents a hydrogen atom, a phenyl group, a hydroxy-C1-6alkyl group, hydroxy-C3-7cycloalkyl group,C1-6an alkoxy group which may be substituted by Ra, C3-7 a cycloalkylaminosulfonyl group, a (6-7) membered monocyclic heterocycloalkylsulfonyl group, with two nitrogen atoms or a nitrogen atom and an oxygen atom in the ring; halogen-C1-3alkoxycarbonylamino group, halogen-C1-3alkylcarbonylamino group, a (5-7)membered monocyclic heterocycloalkanecarbonyl group,containing a nitrogen atom in the ring, and substituted with hydroxy-C1-6alkyl group, or - (CH2)n-C(=O)-NHRf; R2 is a hydrogen atom, a halogen atom or a halogen-C1-3an alkyl group; Ra is C1-6alkylpyrazolyl group, a triazolyl group, a tetrazolyl group or a C1-6 alkylsulfonylpiperazinyl group; Rf is halogen-C1-3alkyl group, hydroxy-C1-6alkyl group, hydroxy-C3-7cycloalkyl group, hydroxy-C3-7cycloalkyl-C1-6alkyl group C1-6alkyl group, substituted by Rfa; Rfa is C a 1-6alkylpyrazolyl group, halogen-C1-3alkylthiazolyl group, an oxadiazolyl group or a halogen-C1-3alkyloxadiazolyl group; and n is an integer from 0 to 3.EFFECT: obtaining of a new compound.20 cl, 5 tbl, 63 ex
Paralytic shellfish poison // 2633637
FIELD: pharmacology.SUBSTANCE: use of paralytic shellfish poison (PSP) for topical treatment of pruritus in a human or other mammal, wherein PSP is a saxitoxin or tricyclic 3,4-propinhydropurine represented by the following formula (I),where R1 and R5 are independently selected from the group consisting of -H and -OH; R2 and R3 are independently selected from the group consisting of -H, -OSO3- and -SO3; and R4 is selected from the group consisting of -H, -OH, -OC(=O)NH2, -OC(=O)NHSO3- and -OC(=O)CH3, or where PSP is the salt of a saxitoxin or tricyclic 3,4-propinhydropurine. Pharmaceutical composition for topical treatment of pruritus in a human or other mammal. A method for topical treatment of pruritus in a human or other mammal.EFFECT: group can effectively treat pruritus in a human or other mammals.22 cl, 1 dwg, 2 tbl
Tricyclic heterocyclic compounds and jak inhibitors // 2632870
FIELD: chemistry.SUBSTANCE: invention relates to a compound represented by the formula : , where the Aa ring is represented by the following formula , where T1a is a nitrogen atom, U1a is a nitrogen atom, Xa is CR9a (where R9a represents a hydrogen atom), Ya a is CR10a (where R10a is a hydrogen atom), R1a is a hydrogen atom, ring Ba is C4-7cycloalkane, benzene or a 4 to 6-membered non-aromatic heterocycle containing 1 heteroatom selected from a nitrogen atom, L1a is a single bond, L2a is a single bond, C1-3 is an alkylene group (C1-3 alkylene group is unsubstituted or substituted by a cyano group) or C1-3 halogenoalkylene group, L3a is a single bond or is represented by any of the following formulas: na is 0 or 1, R3a is a hydroxy group, a halogen atom, a cyano group or a methyl group, the remaining radicals are as defined in the claims. The invention also relates to a compound represented by the formula (Ib), to a JAK inhibitor containing the compound of the invention, to a preventive, therapeutic or improving agent for diseases in which JAK inhibition is effective, to a drug.EFFECT: new compounds with inhibitory activity against JAK are obtained.36 cl, 236 tbl, 611 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
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
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

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
Bicyclic heterocyclic derivatives, their production and application // 2627269
FIELD: pharmacology.SUBSTANCE: invention relates to compounds of general formula (I) , as well as to a method for their preparation, pharmaceutical compositions based thereon, and their application.EFFECT: new compounds have been obtained that can be used to treat or prevent pathology for which it is necessary to inhibit the mTOR kinase.20 cl, 4 tbl, 30 ex
Tienopyrimydine [3,2-d] production, which has inhibitory activity against protein kinases // 2625799
FIELD: chemistry.SUBSTANCE: invention relates to thieno [3,2-d] pyrimidine of formula in which A represents C6-10aryl or 5-10 membered heteroaryl; W represents O, NH or -NHNH-; X and Y are each independently CH or N; Z is hydrogen or NR3R4, wherein said R3 and R4 are each independently hydrogen, C1-6alkyl or - (CH2)q-B, B represents NR5R6 or C3-6cycloalkyl; R1 It represents hydrogen or C1-3alkyl, wherein said alkyl is unsubstituted or substituted by one or more halogen atoms; each R2 independently represents hydrogen, halogen, -CF3-OH, -CN, C1-6alkoxy, C1-6alkyl, C2-4alkynyl, -NR7R8, -NHSO2R9, -SO2R10, -C(O)R11, -NHC(O)R12, -S(O)R14, 5-10 membered heterocycloalkyl, C6-10aryloxy or 5-10 membered heteroaryl, wherein said R2 is attached to A with Using - (CH2)p- or substituted by C1-4alkyl, C2-4alkynyl or one or more halogen atoms; R5, R6, R7, R8, R9, R10, R11, R12 and R14 are each independently hydrogen, -NH2, C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, mentioned alkyl, alkoxy or cycloalkyl being unsubstituted or substituted by one or more halogen atoms; or a pharmaceutically acceptable salt thereof.EFFECT: compounds have inhibitory activity against protein kinases.57 cl, 5 tbl, 128 ex

Compounds of thienyl[3, 2-d]pyrimidine-4-on, method for production, pharmaceutical compositions and their application // 2624021
FIELD: pharmacology.SUBSTANCE: invention relates to new compounds of thienyl[3,2-d] pyrimidin-4-on of general formula pharmaceutical compositions based thereon and their pharmacological applications.EFFECT: new compounds that are inhibitors of DPPIV, which can be used as medicaments for diabetes treatment, have been obtained.15 cl, 12 tbl, 149 ex, 13 dwg
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

Inhibitors of cdk // 2621674
FIELD: pharmacy.SUBSTANCE: invention relates to new compounds of formula Ia or their pharmaceutically acceptable salts, having the properties of cyclin-dependent kinase inhibitor (CDK). The compounds can be used to treat diseases or disorders mediated by CDK, such as a malignant tumor. In the formula Ia R represents hydrogen or C1-C3 alkyl; R1 independently represents phenyl, C C1-C6 alkyl, or two R1 on adjacent ring atoms or on the same ring atom, together with the ring atom(s) to which they are attached, optionally form a 3-8 membered carbocycle; y is 0, 1, 2, 3 or 4; each X independently represents CH or N; and R2 selected from the structures of , , , , , , , , , , , , , , ,mentioned in the claims.EFFECT: improved properties of compounds.16 cl, 8 dwg, 2 tbl, 50 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
Stabilized pemetrexed composition // 2620341
FIELD: pharmacology.SUBSTANCE: composition contains pemetrexed or a pharmaceutically acceptable salt thereof as an active ingredient, N-acetyl-L-cysteine and sodium citrate, wherein the concentration ratio is -30 : 0.15 - 2.0 : 1.0 - 15.0, respectively. The liquid composition can be stored in a solution state. The composition is an injectable liquid composition in an airtight container. The composition is ready for use.EFFECT: combined use of pemetrexed, N-acetyl-L-cysteine and sodium citrate provides a composition that is highly stable and maintained in a clear solution without precipitation during storage.5 cl, 1 dwg, 12 tbl, 16 ex

Solid forms of selective cdk4/6 inhibitor // 2619944
FIELD: pharmacology.SUBSTANCE: invention relates to the crystalline free base of 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one, which is a polymorphic form A with a specific surface area less than or equal to 2 m2/g and a powder X-ray diffraction pattern containing peaks with diffraction angles (2θ) 8.0±0.2, 10.1±0.2 and 11.5±0.2, as well as to pharmaceutical compositions based thereon.EFFECT: free base with larger particle size and improved physicochemical properties is obtained, which can be used for treatment of cell-proliferative diseases such as cancer.13 cl, 9 dwg, 13 tbl, 7 ex

Substituted pyrazolo[1.5-a]pyrido[3.4-e]pyrimidines and their use as proteinquinase inhibitors // 2619932
FIELD: chemistry.SUBSTANCE: invention relates to the use of substituted pyrazolo[1.5-a]pyrido[3.4-e]pyrimidines, characterized by the following formula wherein R1 is hydrogen or phenyl, R2 is hydrogen, R3 is a group selected from ethyl, 2-hydroxyethyl, 3-(N, N-dimethyl)-aminopropyl, 2-(morfilin-4-yl)ethyl, 3-carboxypromyl, 4-methoxybenzamide, ureido, methoxyacetamide 2-pyridin-3-ylmethyl, tetrahydrofuran-2-ylmethyl, 4-chlorobenzyl, 1,2,4-triazol-4-yl, as protein kinase inhibitors possessing anticancer activity.EFFECT: detection of high inhibitory ability of compounds.2 dwg, 13 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

Tetrahydrofolates in combination with egfr inhibitors // 2619335
FIELD: pharmacology.SUBSTANCE: invention is a method for colorectal adenocarcinoma treatment comprising administration of a composition comprising an effective amount of methylenetetrahydrofolate and cetuximab, wherein the method excludes application of 5-FU, its analogs, prodrugs and/or metabolites.EFFECT: potentiation of cetuximab against tumour growth in the absence of 5-FU, as well as expansion of the arsenal for colorectal adenocarcinoma treatment.6 cl, 1 ex, 2 tbl, 4 dwg

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

ethod and improved pharmaceutical composition for acceleration of pde-5 inhibitor transdermal delivery // 2618462
FIELD: medicine, pharmacy.SUBSTANCE: invention refers to medicine and is a transdermal pharmaceutical composition in the form of gel or patch that contains vardenafil, enhancer selected from the group consisting of sodium lauroamphoacetate, quaternium-60, izostearamidopropil morpholine lactate and combinations thereof, and a pharmaceutically acceptable excipient. The enhancer accelerates the kinetics of transdermal absorption of vardenafil. Vardenafil and enhancer are present in the composition in a ratio from 20:1 to 2:1 by weight. The invention also relates to the method of acceleration of the transdermal delivery of vardenafil.EFFECT: invention provides transdermal delivery acceleration due to the vardenafil enhancer.8 cl, 2 ex, 2 dwg
Dioxino- and oxazin-[2,3-d]pyrimidine compounds as phosphoinositide 3-kinase inhibitors and methods for use thereof // 2612251
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I , which are used as inhibitors of phosphoinositide 3-kinase (PI3-kinase), having anticancer activity, anti-inflammatory activity or immunoregulatory properties.EFFECT: technical result is obtaining novel compounds of formula I, as well as pharmaceutical compositions based thereon, which can be used for producing a drug for treating cancer, in particular, cerebral cancer.23 cl, 1 tbl, 41 ex

Compositions in the form of a spray for oral administration and methods of the sildenafil administration // 2611403
FIELD: pharmaceutics.SUBSTANCE: present group of inventions refers to pharmaceutics. Bioavailable composition in spray form for oral administration is described for the treatment of pulmonary arterial hypertension and/or sexual dysfunction induced by selective inhibitors of serotonin reuptake (SIOSR-induced). Specified composition contains sildenafil in the form of its free base or its pharmaceutically acceptable salt, the pH of the composition ranges from 1.5 to 2.4. Also a method for the treatment of pulmonary arterial hypertension and/or SIOSR-induced sexual dysfunction is described.EFFECT: invention provides increased bioavailability of the active substance.26 cl, 20 tbl, 4 ex, 5 dwg
ethod of increasing efficiency of therapy of autoimmune diseases, such as rheumatoid arthritis // 2611341
FIELD: pharmaceutics.SUBSTANCE: group of inventions is disclosed to reduce undesirable reaction of immunosuppressive drugs for treating autoimmune diseases. There are presented: pharmaceutical composition containing iguratimod or its salt and one or more immunosuppressive agents selected from nucleic acid synthesis inhibitors (e.g., methotrexate) or steroid anti-inflammatory drugs (e.g., prednisolone), device and kit of above purpose.EFFECT: technical result consists in reduction of hepatocellular damage and elimination of reticulocytopenia caused by said immunosuppressants.12 cl, 5 tbl, 9 ex
orpholino-substituted derivatives of bicyclic pyrimidine urea or carbamate as mtor inhibitors // 2609208
FIELD: pharmaceutics.SUBSTANCE: invention relates to compounds of formula (I) and their pharmaceutically acceptable salts . In formula (I) m is equal to 1; o equals 1 or 2; each R1 is independently selected from group consisting of H and unsubstituted C1-6alkyl; two R1 are possibly combined to form, together with ring, to which they are bonded, 8-oxa-3-azabicyclo[3.2.1]octane-3-yl or 3-oxa-8-azabicyclo[3.2.1]octane-8-yl ring; T1 is phenyl, where T1 is substituted by group N(R5a)C(O)N(R5bR5) and T1 is optionally additionally substituted with one or more R6, which are identical or different; R6 is halogen; each of R5a, R5b represents H; R5 represents H; T2; and C1-6alkyl, where C1-6alkyl is optionally substituted with one or more R8, which are identical or different; R8 represents halogen or OR9; R9 represents H; T2 is unsubstituted and selected from group consisting of phenyl, pyridyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxetanyl or tetrahydrofuranyl; Ra and Rb are selected to obtain one of formulae (Ik)–(Ip) or Ra, Rb, T1 are selected to obtain formula (Iq) R14, R14a, R14b, R14c are independently selected from group consisting of H; halogen or unsubstituted C1-6alkyl. Compounds of formula (I) possess mTOR inhibiting activity. Invention also relates to pharmaceutical composition containing compounds of formula (I), use of compounds for making drug and to method of treating.EFFECT: novel compounds of formula (I) are obtained, which have mTOR inhibitor activity, which can be used for treating or preventing mTOR related diseases and disorders.16 cl, 15 tbl, 82 ex
Derivatives of carboxylic acids with oxazole[5,4-d]pyrimidine cycle // 2609008
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula I or a physiologically acceptable salt thereof, where A denotes -CH2- or O; X denotes (C1-C6)-alkanediiyloxy group, wherein oxygen atom of (C1-C6)-alkanediiyloxy group is bonded to Y group; Y denotes phenylene, where in phenylene one or more carbon ring atoms are optionally substituted with identical or different (C1-C4)-alkyl; R1 denotes a hydrogen atom; R2 denotes (C1-C6)-alkyl; R3 denotes (C1-C6)-alkyl, wherein alkyl optionally has one or more substitutes in form of fluorine atoms, or R3 is phenyl, where in phenylene one or more carbon ring atoms are optionally substituted with identical or different halogen. Invention also relates to a pharmaceutical composition for activation of EDG-1 receptor, containing at least one compound of formula I or its physiologically acceptable salt and pharmaceutically acceptable carrier.EFFECT: technical result is derivatives of carboxylic acids with oxazole[5,4-d] pyrimidine cycle for use as a medicinal agent for EDG-1 receptor activation.4 cl, 1 tbl, 9 ex

Process for preparation of pemetrexed and lysin salt thereof // 2609006
FIELD: chemistry.SUBSTANCE: invention relates to a method of producing pemetrexed salt, having general formula I, where B+ denotes Na+ or protonated lysine, and having anticancer activity. Method includes following stages: a) reaction of 4-(2-(2-amino-4,7-dihydro-4-oxo-3H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoic acid (2) with diethyl-L-glutamate hydrochloride in presence of a binding agent to produce pemetrexed diethyl ester (3); b) hydrolysis of pemetrexed diethyl ester (3) to pemetrexed acid (5); c) forming salts with a base selected from NaOH or lysine, to produce corresponding pemetrexed salt. Method is characterized by that, that at step a) acid (2) is pre-converted in situ into corresponding sodium carboxylate or morpholine carboxylate, which can be separated or directly react, wherein used reaction solvent consists of water-alcohol mixture of solvents, where alcohol is selected from methanol, ethanol, isopropanol and n-propanol, and an intermediate compound of pemetrexed diethyl ester (3) is directly precipitated from reaction mixture with purity >98 %. Invention also relates to a (bi)lysine salt of N-[4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]-L-glutamic acid (pemetrexed) of formula (1), which is more stable, synthesis method thereof and a pharmaceutical composition containing said salt.EFFECT: method enables to directly precipitate intermediate pemetrexed diethyl ester into a reaction mixture, obtaining said ester with high purity.15 cl, 9 dwg, 3 tbl, 20 ex
Carboxylic acid derivatives, having oxazole[4,5-d]pyrimidine ring // 2609003
FIELD: chemistry.SUBSTANCE: invention relates to a compound of formula I or a physiologically acceptable salt thereof, where A denotes an O atom; X denotes (C3-C7)-cycloalkanediiyl; R1 denotes a hydrogen atom; R2a, R2b and R2c denote hydrogen atoms or (C1-C4)-alkyls; R3 is a radical of unsaturated 6-membered monocycle, wherein one or more carbon atoms contained in cycle optionally have identical or different substitutes R31 or R3 represents a (C3-C7)-cycloalkyl-CuH2u, where u is selected from 1 and 2; R31 denotes a halogen atom or (C1-C4)-alkyl; wherein all alkyls, independently from each other and from other substitutes, can optionally have one or more substitutes in form of fluorine atoms. Invention also relates to a pharmaceutical composition for activation of EDG-1 receptors, containing at least one compound of formula I or its physiologically acceptable salt and pharmaceutically acceptable carrier.EFFECT: technical result is derivatives of carboxylic acids having[4,5-D]pyrimidine ring for use as a medicinal agent for EDG-1 receptor activation.5 cl, 2 tbl, 2 ex

Imidazo[1,2-a]pyridine compounds, synthesis thereof and methods of using same // 2608611
FIELD: chemistry.SUBSTANCE: invention relates to organic chemistry, specifically to novel imidazole derivatives of formula given below or pharmaceutically acceptable salt thereof, where Y denotes CH or N; R1 is: -alkyl containing 1-2 carbon atoms; - substituted alkyl containing 1-3 carbon atoms, which includes 1-3 substitutes, selected from a heteroaryl (selected from pyridine, thiazole furan), phenyl, halogen, wherein said heteroaryl and phenyl are substituted with 1-3 substitutes, selected from halogen, -OQ10, methylsulphonyl group, fluorophenox group and Q15; wherein Q10 is an alkyl containing 1-3 carbon atoms, and Q15 is hydrogen, alkyl containing 1-2 carbon atoms, which can be substituted with three halogen atoms; - cycloalkyl containing 3-6 carbon atoms; - amide (-CONH2) or alkyne containing 2-4 carbon atoms; -halogen; -phenyl; -substituted phenyl, containing 1-2 substitutes, selected from trifluoromethylphenoxy group, -OQ10, halogen, thiomorpholine; wherein Q10 is an alkyl, containing one carbon atom; -benzotriazole; R2 is: -alkyl, containing one carbon atom; -substituted alkyl, containing one carbon atom, containing 1-3 substitutes, selected from halogen and phenyl; -phenyl; R3 is -COW, where W is OR1, NHR1 or NR1R2. Invention also relates to a pharmaceutical composition based on a condensed imidazole derivative and use of said compound.EFFECT: technical result is obtaining novel condensed imidazole derivatives, useful in treatment or prevention of tuberculosis.19 cl, 4 dwg, 5 tbl
Piperazinyl pyrimidine derivatives, preparation method and use thereof // 2608315
FIELD: pharmaceutics.SUBSTANCE: invention relates to piperazinyl pyrimidine derivatives of formula I capable of antagonizing CCR4, method for production thereof, pharmaceutical compositions based thereon, the use of the compounds in the manufacture of a medicament, as well as to a method of treatment. In general formula I any two of A, B and D are N, and the other one is CH; Z is selected from the group consisting of -CH2-, -C(O)-; X is halogen or N, with the proviso that when X is halogen, R1 and R2 in formula I are absent; R1 and R2 are each independently selected from the group consisting of linear or branched alkyl having 1 to 6 carbon atoms, C1-C6 linear or branched heteroalkyl containing 1 to 2 heteroatoms independently selected from the group consisting of O; R3 and R4 are each independently selected from the group consisting of H, phenyl and naphthyl; said phenyl or naphthyl is optionally and independently mono-, di-or poly-substituted with a substituent selected from the group consisting of halogen; R5 is selected from the group consisting of linear or branched alkyl having 1 to 6 carbon atoms, C1-C6 linear or branched heteroalkyl containing 1 to 2 heteroatoms independently selected from the group consisting of S, cycloalkyl group containing 4 to 8 carbon atoms, 5- to 8-membered heterocycloalkyl containing 1 to 2 heteroatoms independently selected from the group consisting of N and S; m and n are each independently 0 or 1.EFFECT: piperazinyl pyrimidine derivatives of formula I capable of antagonizing CCR4 are proposed.7 cl, 2 tbl, 16 ex (I)

Pyrazolopyrimidines and related heterocycles as ck2 inhibitors // 2607453
FIELD: chemistry.SUBSTANCE: invention relates to novel compounds of formula (II) or (II') or pharmaceutically acceptable salts thereof. Compounds inhibit activity of protein kinase CK2 (casein kinase II) or PIM kinase and can be used for treating proliferative diseases selected from cancer of various cell lines, such as breast cancer, lung, skin cancer etc, angiogenesis, as well as other kinase related conditions, including inflammation, vascular diseases, pathogenic infections, neurodegenerative diseases, some immunological diseases. In compounds of formula (II) or (II') or Z3 denotes N and Z4 denotes CR5; or Z3 denotes CR5 and Z4 denotes N; or Z3 and Z4 both denote N; each R5 is independently selected from halo, -CN and -R, where each R is independently selected from H and optionally substituted C1-C4 alkyl; each R2, R3 and R4 is independently selected from H and optionally substituted C1-C10 alkyl; X denotes S or NR2; Y is O or S; Z is O or S; L is a bond, -CR7=CR8-, -C≡C- or -(CR7R8)m-, and W is optionally substituted C1-C10alkyl, optionally substituted with 1-10-member heteroalkyl, optionally substituted C6-C12aryl, Optionally substituted 5-12-member heteroaryl, -NR7R8, -OR7, -S(O)nR7, -CONR7R8, optionally substituted 3-10-member heterocyclyl, optionally substituted with C3-C10carbocyclyl, optionally substituted C2-C10alkenyl, optionally substituted C2-C10alkynyl or -CR7R8R9; or L is a bond, -NR7-, -O-, -S(O)n-, -(CR7R8)m- or -(CR7R8)m-NR7-; and W is selected from optionally substituted C6-C12aryl, optionally substituted 5-12-member heteroaryl and -NR7R8; where each R7 and R8 and R9 is independently selected from H, optionally substituted C1-C10alkyl, optionally substituted 1-10-member heteroalkyl, optionally substituted C3-C10carbocyclyl, optionally substituted 3-10-member heterocyclyl, optionally substituted C3-C10carbocyclylalkyl, optionally substituted 3-10-member heterocyclylC1-C8-alkyl, optionally substituted C6-C12aryl, optionally substituted C7-C12arylalkyl, optionally substituted 5-12-member heteroaryl and optionally substituted 5-12-member heteroarylC1-C8alkyl; or R8 and R9, taken together with carbon atom to which they are bonded form =O(oxo); or R7 and R8, taken together and arranged on one carbon atom or on adjacent bonded atoms (CR7R8)m, either alone, or as part of another group, form a 3-8-member carbocyclic ring or a heterocyclic ring; or R7 and R8, taken together with a nitrogen atom to which they are bonded, form an optionally substituted 5-10-member heterocyclic or heteroaryl ring, which optionally contains one or more additional ring heteroatoms selected from N, O and S; provided that no more than one group from R7 and R8 in -NR7R8 is selected from a group consisting of alkoxy, alkylamino, dialkylamino and heterocyclyl; each n is independently equal to 0, 1 or 2; each m is independently equal to 1, 2, 3 or 4; and R1A is selected from H, optionally substituted C1-C10alkyl; and R1B each is independently selected from H, optionally substituted C1-C10alkyl, optionally substituted 3-10-member heterocyclyl, optionally substituted C3-C10carbocyclyl, optionally substituted C3-C10carbocyclylalkyl, optionally substituted 3-10-member heterocyclyl-C1-C8alkyl, optionally substituted C6-C12aryl, optionally substituted C7-C12arylalkyl, optionally substituted 5-12-member heteroaryl or optionally substituted 5-12-member heteroaryl-C1-C8alkyl.EFFECT: substitutes for saturated and unsaturated carbon atoms are selected from corresponding groups specified in patent claim.58 cl, 14 dwg, 113 tbl, 299 ex
Sulfonamide derivative and medicinal use thereof // 2607081
FIELD: chemistry; pharmaceutics.SUBSTANCE: invention relates to novel sulfonamide derivatives of general formula (1) or pharmaceutically acceptable salts thereof, possessing the properties of inhibition integrin α4β7. In general formula (1) (1), A means a group presented by general formula (2-1) or (2-2) , where Arm is a 5- or 6-member aromatic ring, containing 0, 1 or 2 heteroatoms, selected from nitrogen atoms, R1 and R11, each, independently, represents any substitute selected from a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, mono- or di-lower alkylamino group, R12, R13 and R14, each, independently, represents any substitute selected from a hydrogen atom, lower alkyl group, lower alkoxy group, amino group, lower alkylamino group, low di(alkyl)amino group or (lower alkylamino)lower alkyl group, R2 and R3, each, independently, represents any substitute selected from a hydrogen atom, lower alkyl group or lower alkoxy group, B is represents any substitute selected from lower alkoxy group, optionally substituted by hydroxyl group, lower alkyl group, mono- or di-lower alkylamino group; C3-C6cyclic alkoxy group and/or 6-member(s) heterocyclic(s) group (groups) with an oxygen atom, sulphur atom or a nitrogen atom as heteroatom, hydroxyl group, R41 is represents a hydrogen atom or lower alkyl group, a, b, c and d, each, independently, represents C-R31, C-R32, C-R33 and C-R34 respectively, but one or two of a, b, c and d, each, can be a nitrogen atom, R31, R32, R33 and R34, each, independently, represents any substitute selected from a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, provided that any R31, R32, R33 and R34 represents a halogen atom or lower alkyl group, e, f, g and h, each, independently, represents C-R35, C-R36, C-R37 and C-R38 respectively, however, one or two of e, f, g and h, each, can be a nitrogen atom, R35, R36, R37 and R38, each, independently, represents any substitute selected from a hydrogen atom, lower alkyl group or lower alkoxy group, D represents a phenyl group or a 5 -or 6-member aromatic heterocyclic group, containing a nitrogen atom, an oxygen atom or sulphur atom, optionally containing a substitute(s), selected from a group consisting of hydroxyl groups, lower alkyl groups, lower alkoxy groups, E is a 5- or 6-member heterocyclic group with 1-4 heteroatoms, selected from nitrogen atoms, an oxygen atom and sulphur atom in the cycle, optionally containing a substitute(s), selected from a group consisting of halogen atoms, hydroxyl groups, lower alkyl groups, lower alkoxy groups, amino groups, 4- or 6-member cyclic amino groups, carboxyl groups and lower alkoxy-carbonyl groups; aminocarbonyl group, optionally containing a substitute(s) selected from the group, consisting of hydroxyl groups, lower alkyl groups, lower alkoxy groups, 5- or 6-member heterocyclic groups, containing 1, 2, 3 or 4 heteroatoms, selected from a group consisting of oxygen atoms, sulphur atoms and nitrogen atoms as a component(s) ring atom(s), and substituted by heterocycle of lower alkyl groups, where heterocycle means a 5- or 6-member heterocyclic groups, containing 1, 2, 3 or 4 heteroatoms, selected from group consisting of oxygen atoms, sulphur atoms and nitrogen atoms as a component(s) ring atom(s); hydrogen atom, hydroxyl group, lower alkyl group, lower alkoxy group, amino group, lower alkyl-carbonyl group, lower alkyloxy-carbonyl group or a lower alkylaminoalkilen group, and provided that the lowest alkyl-carbonyl group and the lowest alkyloxycarbonil group can be, each of which, are connected to a phenyl group, presented D, to form condensed ring.EFFECT: compounds can be used for treating or preventing an inflammatory disease, in which the pathological condition associated with indirect by integrins α4β7 adhesion process.15 cl, 2 tbl, 258 ex
Novel compound having parp inhibitory activity // 2606635
FIELD: chemistry.SUBSTANCE: invention relates to novel compounds of general formula 1 or pharmaceutically acceptable salts thereof, which posses PARP (poly(ADP-ribose)polymerase) inhibitor properties. Compounds can be used for prevention or therapy of posterior eye diseases. In formula (1) R1 is a halogen atom; R2 and R3 represent a hydrogen atom; R4 and R5 represent a hydrogen atom or a deuterium atom, or R4 and R5 can form an oxo group; Ra is a hydrogen atom or lower alkyl group, and Rb is a phenyl group or lower alkyl group, substituted with di-(lower alkyl) amino group, or 5-6-member heterocyclic group containing 1-2 heteroatoms in ring, selected from nitrogen atoms or nitrogen atom and an oxygen atom or a phenyl group, or 6-member nitrogen-containing heteroaryl group; Ra and Rb can be bonded with each other to form a 5-7-member nitrogen-containing heterocyclic ring, which can contain an additional nitrogen atom, optionally condensed with a benzene ring and optionally substituted with a group, selected from lower alkyl group, lower haloalkyl group, lower cycloalkyl group, lower cycloalkylcarbonyl group, lower alkoxycarbonyl group, low-cycloalkyl-lower alkyl group, di-(lower alkyl) amino group, di-(lower alkyl) amino-lower alkoxy group; phenyl group or phenyl-lower alkyl group, in each of which phenyl group can be substituted with 1–2 halogen atoms, hydroxy group, lower alkyl group, lower haloalkyl group, lower alkoxy group, C1-C2alkylenedioxy group; 5-6-member heterocyclic group, containing 1–2 heteroatoms in ring, selected from nitrogen atom, oxygen atom and sulphur atom, and/or nitrogen atom and oxygen atom, optionally substituted with a halogen atom and optionally condensed with a benzene ring or pyridine ring; ring A is a benzene ring or thiophenyl ring; and m is 0 or 1.EFFECT: obtaining novel compounds.12 cl, 61 tbl, 7 ex

Substituted purine and 7-deazapurine compounds // 2606514
FIELD: pharmaceutics.SUBSTANCE: invention relates to compound of formula (IV) or its N-oxide, or pharmaceutically acceptable salt of such compounds, where A is O or CH2; Q is NH2, NHRb, NRbRc or OH, where each Rb and Rc independently represent C1-C6 alkyl; X is N or group CRx, where Rx is H; Y is H or Rd, where Rd is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or C3-C8 cycloalkyl, and Rd is optionally substituted with one or more substitutes, selected from group consisting of halogen and C3-C8 cycloalkyl; each of R1 and R2 is H; each of Re, Rf, Rg and Rh independently represent group -M2-T2, where M2 is bond or O-C1-C4 alkyl linker, and T2 is H, halogen or RS4, where RS4 is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl or oxetanyl, and each of O-C1-C4 alkyl linker and RS4 is optionally substituted with one or more substitutes, selected from group consisting of halogen, hydroxyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl and C1-C6 alkoxyl; and m equals to 0, 1 or 2. Invention relates to specific compounds. Disclosed compounds are intended for producing pharmaceutical composition with antiproliferative activity, including therapeutically effective amount of compound and pharmaceutically acceptable carrier. Besides compound is applied for treating leukemia and inhibiting DOT1L-mediated protein methylation.EFFECT: substituted purine or 7-deazapurine compound effective in treating leukemia and inhibiting DOT1L-mediated protein methylation.24 cl, 1 tbl, 3 dwg, 11 ex
(z)-ethyl2-(4-(4-chlorophenyl)-2,4-dioxo-3-(3-oxo-3,4-dihydroquinoxalin-2(1h)-ylidene)butanamido)-4-methyl-5-phenylthiophene-3-carboxylate having antidiabetic activity, and method for production thereof // 2606230
FIELD: chemistry.SUBSTANCE: invention relates to a novel (Z)-ethyl 2-(4-(4-chlorophenyl)-2,4-dioxo-3-(3-oxo-3,4-dihydroquinoxalin-2(1H)-ylidene)butanamido)-4-methyl-5-phenylthiophene-3-carboxylate having anti-diabetic activity, and a method for production thereof.EFFECT: task of invention is widening range of means of impact on living organism. 4 cl, 5 tbl, 3 ex
Novel immune system modulators related applications // 2606114
FIELD: chemistry.SUBSTANCE: invention relates to novel compounds of formula I or a pharmaceutically acceptable salt thereof, which possess properties of TOLL-like receptor (TLR9) inhibitor and can be used for treating autoimmune diseases, mediated by TLR9 activity. Diseases can be selected from cutaneous and systemic lupus erythematosus, insulin-dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis, atherosclerosis, psoriasis, psoriatic arthritis, inflammatory bowel disease, ankylosing spondylitis, autoimmune hemolytic anemia, Behget's syndrome, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's thyroiditis, idiopathic thrombocytopenia, myasthenia gravis, pernicious anemia, polyarteritis nodosa, polymyositis/dermatomyositis, primary biliary sclerosis, sarcoidosis, sclerosing cholangitis, Sjogren's syndrome, systemic sclerosis (scleroderma and CREST syndrome), Takayasu's arteritis, temporal arteritis, and Wegener's granulomatosis. In Formula I X is absent or denotes aryl; Q is H, (CH2)qNR1R2, SR1 or CR1R2R2', where q is equal to 0 or 1; R1, R2 and R2', each independently, represent hydrogen, C1-C12 alkyl, or R1 and R2 together with a nitrogen atom, with which they are bonded form a 6-member heterocycle, containing two nitrogen atoms or a nitrogen atom and an oxygen atom, which can be optionally substituted with (C1-C4)alkyl or (CH2)pORa, where p is equal to 2-4; R7 is NR3R4; R3 and R4, each independently represent (C1-C12)alkyl, or R3 and R4, together with a nitrogen atom with which they are bonded, form or 6-member heterocycle containing 1-2 heteroatoms selected from a group consisting of O and N, and which can be optionally substituted with (C1-C4)alkyl; Y is NR11, where R11 is hydrogen or (C1-C12)alkyl; L is an alkyl or alkenyl, each containing from 2 to 10 carbon atoms; R5 is hydrogen, halogen, CF3, ORa, SRa, NRbRc or NH(CH2)pNRbRc; R6 is a halogen, (C1-C12)alkyl, CF3, phenyl, phenyl substituted with halogen, CN or CF3, or NH(CH2)pNRbRc; in each case Ra independently represents hydrogen, (C1-C6)alkyl; and said Rb and Rc, together with a nitrogen atom with which they are bonded, optionally form 5-6-member heterocycle, containing 1-2 heteroatoms selected from O and N, where heterocycle is optionally substituted with (C1-C4)alkyl; provided that if R5 and R6 denote H or methyl, then Q is not H.EFFECT: obtaining novel compounds of formula.19 cl, 5 tbl, 73 ex

Novel thieno-pyrimidine derivatives, method for production thereof and pharmaceutical compositions containing them // 2605403
FIELD: chemistry.SUBSTANCE: invention relates to compounds of formula (I): (I), in which: A is a linear or a branched (C1-C6)alkyl group, a linear or a branched (C1-C6)alkoxy group, a -S-(C1-C6)alkyl group, a linear or a branched (C1-C6)polyhalogen-alkyl group, a hydroxy group, a cyano group or a halogen atom; R1, R2, R3, R4 and R5 independently denote a hydrogen atom, a halogen atom, a linear or a branched (C1-C6)alkyl group, a linear or a branched (C2-C6)alkenyl group, a linear or a branched (C2-C6)alkynyl group, a linear or a branched (C1-C6)polyhalogen-alkyl group, a hydroxy group, a linear or a branched (C1-C6)alkoxy group, a -S-(C1-C6)alkyl group, a nitro group, -alkyl(C0-C6)-NR8R8′, -O-Cy1, -alkyl(C0-C6)-Cy1, -alkenyl(C2-C6)-Cy1, -alkynyl(C2-C6)-Cy1, -O-alkyl(C1-C6)-R9, -C(O)-OR8, -O-C(O)-R8, -NR8-C(O)-R8′, -NR8-C(O)-OR8′, -alkyl(C1-C6)-NR8-C(O)R8′; X represents a carbon or a nitrogen atom; R6 represents hydrogen, a linear or a branched (C1-C8)alkyl group, an aryl group, heteroaryl-alkyl(C1-C6); R7 is a linear or a branched (C1-C6)alkyl group, a linear or a branched (C2-C6)alkenyl group, a linear or a branched (C2-C6)alkynyl group, -Cy3, -alkynyl(C2-C6)-Cy3,-Cy3-Cy4, -alkynyl(C2-C6)-O-Cy3, -Cy3-alkyl(C0-C6)-O-alkyl(C0-C6)-Cy4, a halogen atom, a cyano group, -C(O)-R11, -C(O)-NR11R11′, values of other radicals are defined in cl.1 of the formula.EFFECT: compounds can be used as pro-apoptotic agents.50 cl, 2 tbl, 871 ex

Derivatives of 1-(3-aminophenyl)-6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-1h,6h-pyrido[4,3-d]pyrimidine-2,4,7-trione as mek1/2 inhibitors // 2605400
FIELD: chemistry.SUBSTANCE: present invention relates to novel derivatives of 1-(3-aminophenyl)-6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-1H, 6H-pyrido[4,3-d]pyrimidine-2,4,7-trione, having effect on kinase MEK1 and can be used for treating and preventing cancer, in particular malignant melanoma. Said derivatives are selected from following group of compounds: N-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminoacetamide hydrochloride (1.1), N-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminopropionamide hydrochloride (1.4), N-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminobutyramide hydrochloride (1.7), (R)-{3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-2-dimethylaminopropionamide hydrochloride (1.10), {3-[6,8-dimethyl-5-(4-iodo-2-fluoro-phenylamino)-3-cyclopropyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]-phenyl}-amide(R)-1-methylpyrrolidine-2-carboxylic acid hydrochloride (1.14). Invention also relates to a method of producing said compounds.EFFECT: method consists in that compound of formula 2 or salt thereof: , where R2 is a hydrogen atom, reacts with corresponding organic acid or an activated derivative thereof, with subsequent treatment of obtained product with hydrogen chloride solution.11 cl, 1 tbl, 7 ex
 
2551204.
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