Thiophene derivatives as snk 1 inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (II) and to their pharmaceutically acceptable salts. In formula R1 means phenyl optionally substituted on one or more carbon atoms with one or more R9; where R9 is specified of halogen, amino, C1-6alkyl and C1-6alkoxy, one of R2 and R3 represents -C(=O)NR6R7, and the other represents -NHC(=O)NHR4; R4 and R6 represent N, and R7 represents piperidine-3-yl. Besides the invention refers to a pharmaceutical composition containing the compound of the invention, to application of the compound for preparing a drug, and also to an intermediate compound of formula (XI) or its salts, where A represents thienyl ring.

EFFECT: preparation of new compounds exhibiting inhibitory properties with respect to SNK1 kinase.

7 cl, 263 ex, 1 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula (II) or its pharmaceutically acceptable salt
,
in which R1denotes phenyl, which is optionally substituted on one or more carbon atoms by one or more R9; where R9selected from halogen, amino, C1-6the alkyl and C1-6alkoxy,
one of R2and R3represents-C(=O)NR6R7and the other represents-NHC(=O)other4;
R4and R6represent H, and
R7represents piperidine-3-yl.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, where R2represents-NHC(=O)other4, a R3represents-C(=O)NR6R7.

3. The compound according to claim 1, which is (S)-piperidine-3-alamid 5-(3-fluoro-phenyl)-3-ureido-thiophene-2-carboxylic acid or its pharmaceutically acceptable salt.

4. The compound according to claim 1, which is (S)-piperidine-3-alamid 5-phenyl-2-ureido-thiophene-3-carboxylic acid or its pharmaceutically acceptable salt.

5. Pharmaceutical composition having properties kinase inhibitor SNK 1, containing a compound of the formula (II) or its pharmaceutically acceptable salt according to any one of claims 1 to 4, together with at least one pharmaceutically acceptable carrier, diluent or order the selection.

6. The use of the compounds of formula (II) or its pharmaceutically acceptable salt according to any one of claims 1 to 4 for the preparation of a medicinal product used in the inhibition of the activity of the kinase SNK 1.

7. The intermediate compound of formula (XI) or its salt

where R1denotes phenyl, which is optionally substituted on one or more carbon atoms by one or more R9; where R9selected from halogen, amino, C1-6the alkyl and C1-6alkoxy,
R6represent H,
R7represents piperidine-3-yl, and
Rather it represents a thienyl ring to obtain the compounds of formula (II) according to any one of claims 1 to 4.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula (1) , where substitutes are as defined in paragraph 1 of the invention. The compounds have fungicide properties. The method of obtaining formula (1) compounds is described, in which n equals 0. Described also is a fungicide composition based on formula (1) compounds and a phytopathogenic fungus control method which uses compounds in paragraph 1 or a composition based on the said compounds.

EFFECT: obtaining novel compounds which can be used as fungicides.

24 cl, 312 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1), their tautomers and pharmaceutically acceptable salts. The disclosed compounds have thromobopoietin receptor agonist properties. In formula (1) , A is a nitrogen atom or CH, when A is a nitrogen atom, B is NR9 (where R9 is a C1-10 alkyl group), and when A is CH, B is a sulphur atom, R1 is a phenyl group (the phenyl group is substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-10 alkyl groups and C1-10 alkoxy groups (C1-10 alkyl groups and C1-10 alkoxy groups are unsubstituted or substituted with one or more halogen atoms)), L1 is bond, X is OH, R2 is a C1-10 alkyl group, L2 is a bond, L3 is NH, L4 is a bond or NH, Y is a sulphur atom, and when L4 is a bond, R3 is a piperidinyl group, a piperazinyl group (the piperidinyl group and the piperazinyl group are substituted with substitutes selected from a group containing C1-10 alkoxycarbonyl groups, carboxyl group, hydroxyl groups, di-C1-10 alkylaminocarbonyl groups, C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups (C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups are substituted with a substitute selected from a group containing pyridyl groups, hydroxyl groups and carboxyl groups)), or when L4 is NH, R3 is a C1-10 alkyl group (C1-10 alkyl group is substituted with a substitute selected from a group containing C1-10 alkoxy groups, C1-10 alkoxycarbonyl groups or carboxyl groups).

EFFECT: obtaining a thrombopoietin receptor activator which is a formula (1) compound and a medicinal agent which contains the disclosed compound as an active ingredient.

10 cl, 3 tbl, 47 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to organic chemistry and specifically to compounds of formula I or to pharmaceutically acceptable salts thereof, where Ar is imidazole or pyrazole, where the said Ar can be substituted with substitute(s) selected from a group consisting of a C1-C6 alkyl group, a phenyl group and a halogen atom, each of Y1, Y2 and Y3 is a carbon ot nitrogen atom, A is an oxygen atom, a sulphur atom or a group of formula -SO2-, R1 is a hydrogen atom, a C1-C6 alkyl group which can be substituted with one phenyl group (where the said phenyl group can be substituted with one substitute selected from a group consisting of a halogen atom and a C1-C6 alkyl group), or a phenyl group, R2 is a C1-C6 alkyl group, R3 is (i) a C1-C18 alkyl group, (ii) C2-C8 alkenyl group, (iii) C2-C8 alkynyl group, (iv) C3-C8 cycloalkyl group, (v) C1-C6 alkyl group substituted with 1-3 substitutes selected from a group given in paragraph 1 of the formula of invention, or (vi) a phenyl group, a naphthyl group, a pyrazolyl group, a pyridyl group, an indolyl group, a quinolinyl group or an isoquinolinyl group, where each of the said groups can be substituted with 1-3 substitutes selected from a group given in paragraph 1, R4 is a hydrogen atom or a C1-C6 alkyl group, and R5 is (i) C1-C10 alkyl group, (ii) C1-C10 alkyl group which is substituted with one or two substitutes selected from a group given in paragraph 1, (iii) C2-C8 alkenyl group which can be substituted with a phenyl group, or (iv) phenyl group, naphthyl group, thienyl group, pyrrolyl group, pyrazolyl group, pyridyl group, furanyl group, benzothienyl group, isoquinolinyl group, isoxazolyl group, thiazolyl group, benzothiadiazolyl group, benzoxadiazolyl group, phenyl group, condensed with a 5-7-member saturated hydrocarbon ring which can contain one or two oxygen atoms as ring members, uracyl group or tetrahydroisoquinolinyl group, where each of the said groups can be substituted with 1-5 substitutes selected from a group given in paragraph 1, provided that when Ar is a group of formula 5, which can be substituted with a C1-C6 alkyl group, R5 is not a C1-C10 alkyl group, and the formula (I) compound is not 5-(3,5-dichlorophenylthio)-4-isopropyl-2-methane-sulfonylaminomethyl-1-methyl-1H-imidazole or 5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-2-p-toluene-sulfonylaminomethyl-1H-imidazole. The invention also relates to a pharmaceutical composition based on the formula I compound and to formula II compounds, radicals of which are defined in the formula of invention.

EFFECT: obtaining novel compounds with inhibitory effect on the bond between S1P and its Edg-1 (SIP1) receptor.

32 cl, 43 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of the formula (I): , where R1 is C1-C8alkyl optionally substituted with one to three substitutes selected out of substitute group A; R2 is C1-C6alkyl or C1-C6alkoxyC1-C6alkyl; R3 is C1-C6alkyl or C1-C6alkoxy; or R2 and R3 together with adjoining carbon atoms form optionally substituted non-aromatic 5-10-member carbon ring; R4 is hydrogen; G is group represented by the formula: or the rest as provided in the invention claim; and to pharmaceutical composition, application of claimed compounds, and method of atopic dermatitis prevention or treatment.

EFFECT: novel compounds useful as atopic dermatitis treatment medication and antipruritic medicines.

24 cl, 75 ex, 290 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to cyclic derivatives of aminobenzoic acid and to their pharmaceutically acceptable salts of general formula , in which ring Ar is a phenyl group, a 5-member aromatic heterocyclic group containing 1-2 heteroatoms selected from nitrogen, sulphur and oxygen, or a benzothiazolyl group; where the said groups can have 1-2 substitutes selected from a group comprising lower alkyl; a phenyl group; a phenyl group substituted with 1-2 halogens; a phenyl group substituted with a lower alkoxy group; a phenyl group substituted with a halogen-substituted lower alkyl group; a phenoxy group substituted with a halogen; a halogen; Z is an oxygen atom or -(CH2)-n (where n equals 0, 1 or 2); Y is C1-C4 alkylene, C2-C4 alkenylene or general formula (2) -T-A-U- (2) in which T is a single bond, C1-C4 alkylene or C2-C4 alkenylene; U is single bond, C1-C4 alkylene; values of the rest of radicals are given in the formula of invention.

EFFECT: obtaining a PPARα, agonist which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid, and an agent which reduces the level of lipids which contains an active ingredient in form of at least one cyclic derivative of aminobenzoic acid.

12 cl, 16 tbl, 184 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new imidazole derivatives of general formula I , where R1 is C1-C10alkyl or C3-C10cycloalkyl, each possibly and independently substituted with 1 substitute selected from C3-C10cycloalkyl or aryl or a heteroaryl group, possibly substituted with one or two halogens; aryl or heteroaryl; R2 is C1-C10alkoxy or C1-C10thioalkyl; R3 is C1-C10alkoxy, possibly substituted with one C1-C10alkoxy or nitrile, where the said alkoxy group can be cyclic or can contain one O heteroatom; R4 is C1-C10alkyl; C2-C10alkenyl; C1-C10alkoxy or C3-C10cycloalkyl, each possibly and independently substituted with 1 or 2 substitutes selected from C1-C10alkoxy, C3-C10cycloalkyl, carboxylic ester, or with one or two aryl or heteroaryl groups, possibly substituted with one substitute selected from C1-C10alkyl, C3-C10cycloalkyl, nitro or halogen; aryl or heteroaryl, each possibly and independently substituted with 1-3 substitutes selected from C1-C10alkyl, C3-C10cycloalkyl, C1-C10alkoxy, phenoxy, thiophenyl, halogen, nitro, nitrile or aryl group, possibly substituted with one halogen; where up to three hydrogen atoms of the alkyl group can be substituted with fluorine atoms; where the said cycloalkyl can independently have one or two carbon atoms substituted with O or N; where the said aryl denotes an aromatic ring having 6 to 10 carbon atoms, including mono- and bicyclic compounds; and where the said heteroaryl denotes an aromatic ring having 3 to 10 carbon atoms, including mono- and bicyclic compounds in which one to three ring atoms are oxygen, nitrogen or sulphur atoms; except compounds given in paragraph 1. The invention also pertains to use of the said compounds for making a medicinal agent, a treatment and prevention method, a compound of formula II (values of radicals are given in the formula of invention).

EFFECT: new imidazole derivatives having positive allosteric modulator effect on GABAB receptor are obtained.

30 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 1-thio-D-glucitol compounds of formula I or to pharmaceutically acceptable salts thereof or hydrates of the compound or salts: , [where R1, R2, R3 and R4 are identical or different, and each is a hydrogen atom, C1-C6-alkyl group), A is -(CH2)n-, -CONH(CH2)n-, -O- or -(CH2)nCH=CH- (where n is an integer from 0 to 3, Ar1 is an arylene group, heteroarylene group, which is an unsaturated 5-9-member mono- or bicyclic group, containing 1-2 heteroatoms, selected from S and N, Ar2 is an aryl group or heteroaryl group which is an unsaturated 5-9-member mono- or bicyclic group containing 1-2 heteroatoms selected from O, S and N, and R5, R6, R7, R8, R9 and R10 are identical or different, and each is (i) a hydrogen atom, (ii) a halogen atom, (iii) a hydroxyl group, (iv) C1-8-alkyl group, optionally substituted with hydroxyl group(s), (v) -(CH2)m-Q {where m is an integer from 0 to 4, and Q is -CO2H, -ORc1, -CO2Ra3, -SRe1, -NHRa6 or -NRa7Ra7 (where each of Ra3, Ra6 and Ra7 is a C1-6-alkyl group, Rc1 is a C1-6-alkyl group, and Rc1 is a C1-6-alkyl group)}, (vi) -O-(CH2)m'-Q' {where m' is an integer from 1 to 4, and Q' is a hydroxyl group,-CO2H, -CO2Ra8, -CONRa10Ra10, -NRa12Ra12 (where each of Ra8, Ra10 and Ra12 is a C1-6-alkyl group)}, (vii) -ORf {where Rf is C3-7-cycloalkyl group or tetrahydropyranyl group)}, (viii) morpholine group, (ix) phenyl group, (x) pyridyl group]. The invention also relates to 1-thio-D-glucitol compounds of formulae IA, II, III, IV, to a pharmaceutical agent, to methods of obtaining 1-thio-D-glucitol compounds, as well as to compounds of formulae XIII, XIV.

EFFECT: obtaining novel biologically active compounds which are inhibitors of sodium-dependent co-transporter-2-glucose.

25 cl, 140 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: described are novel thiophene derivatives of formula (1) and pharmaceutically acceptable salts thereof, where A is -CH2CH2-, -NH-CH2-, -CH2-O or -CH2NH-, R1 is hydrogen or alkyl, when X is C-R4, R1 additionally represents halogen, and when A is -CH2-CH2- or -CH2NH, R1 additionally represents alkoxy, R2 is hydrogen, alkoxy, fluoralkoxy, hydroxyalkoxy, hydroxyalkyl, di-(hydroxy)alkoxy, pyridinyl-3-methoxy, pyridinyl-4-methoxy, R3 is hydrogen, alkyl, trifluoromethyl, and when X is C-R4, R3 additionally represents halogen, and when A is -CH2-CH2-, R3 additionally represents alkoxy, X is N or C-R4, R4 is hydrogen, alkyl, alkoxy or halogen, R5 is methyl or ethyl. Also described are isomers of the said compounds, an initial compound for synthesis of formula (1) compound, which has agonistic effect on S1P1/EDG1 receptors, as well as a pharmaceutical composition based on formula (1) compound and use of formula (1) compound.

EFFECT: obtaining a pharmaceutical composition for preventing or treating diseases or disorders associated with activated immune system.

19 cl, 2 tbl, 167 ex

FIELD: chemistry.

SUBSTANCE: described is a compound selected from a group consisting of formula II formula III and formula IV , or its salt or ester, where G1 is selected from a group which includes - (CR1R2)n-, n equals 0 or 1; R1 and R2 are independently selected from a group which includes hydrogen; X1, X2 and X3 are independently selected from a group consisting of hydrogen, optionally substituted lower alkyl, halogen, optionally substituted lower alkoxy, G2 is a heterocycloalkyl linker optionally substituted with X4 and X5, where the heterocycloalkyl linker is selected from a group consisting of piperazinyl, 3,6-dihydro-2N-pyridinyl, [1,4]diazepanyl, 3,9-diazabicyclo[3,3,1]nonyl; X4 and X5 are independently selected from a group consisting of hydrogen and optionally substituted lower alkyl; CO2R; R is selected from a group consisting of optionally substituted lower alkyl and hydrogen; G3 is a bond; G4 is selected from a group consisting of hydrogen, aryl, selected from phenyl which is optionally substituted with a lower alkyl, halogen, lower haloalkyl or lower haloalkoxy; heteroaryl selected from pyridinyl which is optionally substituted with a halogen or lower haloalkyl; and optionally substituted cycloheteroalkyl selected from 1,3-benzodioxolyl. Described also are specific compounds and a pharmaceutical composition.

EFFECT: disclosed compounds are used as modulators of receptors activated by a peroxisomal proliferator.

5 cl, 2 tbl, 117 ex

FIELD: chemistry.

SUBSTANCE: novel compound is N-(5-hydroxy-2,4-di-tert-butylphenyl)-4-oxo-1H-quinoline-3-carboxamide or its pharmaceutically acceptable salts. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with CFTR activity modulation properties.

2 cl, 485 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described compounds of formula I: , their pharmaceutically acceptable salts where R1-R7, Y and n are specified in the patent claim. The compounds exhibit inhibitory action in the relation to aurora A tyrosine kinase. There is also described a drug of the compound of formula (I). The drug can be used for control or prevention of diseases, such as cancer.

EFFECT: preparation of new phthalazinone derivatives which can be used for control or prevention of diseases, such as cancer.

17 cl, 2 tbl, 41 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and concerns methods and compositions for improving effectiveness of antibody for medical application with using the compounds potentiating NK-cells. Substance of the invention covers a method of treating a disease and a pharmaceutical composition for treating a disease brought on or exacerbated partially by the cells which can be considered as targets and which can be eliminated by antibody for medical application, involving introduction to a patient of the first antibody blocking an inhibiting NK-cell receptor chosen of group: KIR2DL1, KIR2DL2, KIR2DL3 and NKG2A and then introductions of antibody for medical application.

EFFECT: advantage of the invention consists in higher clinical effectiveness.

40 cl, 2 ex, 1 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to molecular and experimental oncology and represents a pharmaceutical combination for simultaneous, separate or consecutive introduction which contains substrata phosphorylation site inhibitor CK2 which includes peptide P15 (CWMSPRHLGTC) together with a cytostatic agent pharmaceutically acceptably mixed with the appropriate carriers.

EFFECT: invention provides higher therapeutic index of current cytotoxic agent, by reducing an effective dose and natural toxicity exhibited by the medicines of such type, and evasion of chemical stability of a tumour with respect to conventional cytotoxic agents.

12 cl, 4 ex, 4 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to experimental medicine, namely to experimental oncology, can be used for treating oncological diseases. A method involves cytostatic chemotherapy of tumours with cyclophosphan and introduction of a drug of herbal raw material. Said drug of herbal raw material is represented with an agent containing peat, humic acids and fulvic acids, amino acids, vitamins, macro-and microelements and prepared by peat processing with ammonia and hydrogen peroxide added at 140°C. The peat agent is introduced into food or potable water at a daily dose 100-200 mg/kg.

EFFECT: use of the invention allows intensifying anticancer and antimetastatic effects of cyclophosphan, lowering its haematotoxicity.

2 cl, 6 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: given invention refers to medicine and concerns a combination for treating an oncological disease, containing as an active ingredient, at least one immunostimulating drug of general formula and one or more chemotherapeutic agents chosen from the group consisting of alkylating agents including carboplatin, cisplatin and oxaliplatin, cytostatic agents chosen from cyclophosphamide and its derivatives, and antimetabolites chosen from fluorouracila and its derivatives, and to a method of treating oncological conditions.

EFFECT: invention provides higher clinical effectiveness.

18 cl, 8 dwg, 5 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to a pharmaceutical agent for urinary bladder cancer treatment containing EO9 in the solution with propylene glycol (PG) concentration chosen from the group consisting of approximately 30% volume/volume of PG, approximately 20% volume/volume of PG and approximately 10% volume/volume of PG.

EFFECT: there is offered method of treating of urinary bladder cancer.

24 cl, 1 tbl, 2 ex, 9 dwg

FIELD: medicine.

SUBSTANCE: invention refers to drugs and concerns a pharmaceutical combination containing the effective amount of an anticancer compound, representing VEGF Trap , in combination with the effective quantity of combretastatin derivative chosen of: combretastatin A-4, a product of formula and combretastatin derivative of formula for treating solid tumours.

EFFECT: combinations according to the invention provide essential reduction of tumour volume development in comparison with separate introduction of each compound.

3 cl, 1 tbl

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology, specifically to obtaining genetically engineered vaccines and can be used in medicine. A recombinant gene structure containing a series of human SLC gene, antigen gene and gene Fc-fragment of IgG 1 is obtained.

EFFECT: invention considerably increases efficiency of the immune response of the body to the introduced antigen compared to existing antigen structures.

10 cl, 15 dwg, 1 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to biotechnology, specifically to compositions able to inhibit the growth of tumour cells of various histological origins and activated endothelial cells, and can be used in medicine. Components of the specified compositions are non-proteolytic polypeptide fragments of serralysines chosen from ARA1, ARA2, ARA3 and ARA4. Specified fragments of serralysines are also combined with prodigiosins and with antibodies or their antigen-binding fragments directed on antigens of tumour cells that intensify the anticancer effect of the composition.

EFFECT: invention allows preparing the composition with higher antiproliferative activity, in comparison with a composition containing the whole molecules of serralysines.

8 cl, 16 dwg, 7 tbl, 21 ex

FIELD: chemistry.

SUBSTANCE: in the compound of general formula R1 represents halogen, C1-4alkyl, or C1-4alkoxy; R2 represents hydrogen, halogen; R3 represents hydrogen, or one or several halogens; R4 represents hydrogen, halogen, R8 or Y1R8; Y1 represents -NRa-; Ra and Rb are similar or different, and each represents hydrogen or C1-4alkyl; R8 represents hydrogen, C1-10alkyl; R7 represents hydrogen, hydroxy, trifluoromethyl, amino, C1-6hydroxyalkyl, C1-4alkoxy, C1-4alkylthio, C1-6alkylamino, C1-4alkoxycarbonyl, -S(O)2R, -COOH, -CONH2, or -NRaC(O)R', where R and R' are similar or different, and each represents hydrogen or C1-3alkyl; R5 represents -COOH, Y2R9, Y2R9Y3R10, C1-6alkyl-Y2R9, C1-10alkyl, or unsaturated C3-8carbocycle, said R5 is substituted with one or several, similar or different substituents, represented by R7; R6 represents hydrogen; Y2 represents -O-, -NRa-, -NRaC(O)NRb-, -NRaC(O)-, -C(O)NRa-, -C(O)-, -NRaC(O)O-, or -OC(O)-; R9 represents C1-10alkyldioxolanyl, C1-10alkylthiazolyl, C1-10alkylmorpholinyl, etc.

EFFECT: obtaining novel compounds, represented by formula I, which possess properties of TNF-α or MAP-kinase p38a inhibitors for obtaining medication to be applied as anti-inflammatory or anti-cancer agent.

24 cl, 4 tbl, 270 ex

FIELD: chemistry.

SUBSTANCE: invention relates to inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), their enatiomers, racemates and pharmaceutically acceptable salts, as well as a pharmaceutical composition based on said inhibitors and method of treating, preventing or suppressing inflammation and other conditions which are mediated by activity of leukotriene A4-hydrolase. In general formula (II) , X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is O; Z is chosen from a group which consists of O and a bond; W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to the nitrogen atom which is bonded to the said W; R4 is chosen from a group which consists of H, OCH3 and Cl; R6 is H or F; and R2' and R3' are each independently chosen from a group which consists of: A) H, C1-7alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-7alkyl, where each of substitutes (A) is independently substituted with 0 or 1 RQ, where each of said RQ is a carbon atom substitute, which is at least one carbon atom, separate from nitrogen atom; B) HetRa substitute; C) -C1-7alkyl-C(O)Rx; H) -C0-4alkyl-Ar5, where Ar5 is a 5-member heteroaryl, which has one heteroatom, chosen from a group >NRY, and 0 or 1 additional heteroatom -N=, and optionally contains two carbonyl groups, and optionally benzo-condensed; I) -C0-4alkyl-Ar5' , where Ar5' is a 5-member heteroaryl, which contains 3 or 4 nitrogen atoms; M) SO2C1-4alkyl; alternatively, R2' and R3', taken together with a nitrogen atom with which they are bonded, form a heterocyclic ring which contains at least one heteroatom, which is the said bonded nitrogen atom, where the said heterocyclic ring is chosen from a group which consists of i) 4-7-member heterocyclic ring HetRb, where the said 4-7-member heterocyclic ring HetRb has one heteroatom, which is the said bonded nitrogen atom, and is substituted with 0, 1 or 2 identical or different substitutes, where the said substitutes are chosen from a group which consists of -RY, -CN, -C(O)RY, -C0-4alkyl-CO2RY, -C0-4alkyl-C(O)CO2RY, -C0-4alkyl-ORY, -C0-4alkyl-C(O)NRYRZ-, -C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY, -C0-4alkyl-NRYCO2RY, -C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4alkyl-NRWSO2RY, 1,3-dihydrobenzoimidazol-2-on-1-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol- 5-yl, -C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY, -C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, , ,; ii) 5-7-member heterocyclic ring HetRC which has one additional heteroatom separated from the said bonded nitrogen atom by at least one carbon atom, where the said additional heteroatom is chosen from a group which consists of O, S(=O)2 and >NRM, where the said 5-7-member heterocyclic ring HetRC has 0 or 1 carbonyl group and is substituted with 0, 1 or 2 substitutes at identical or different substituted carbon atoms, where the said substitutes are chosen from a group which consists of -C(O)RY and RZ; iii) one of 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl is substituted at the carbon atom by 0 or 1 substitute such as -C0-4alkyl-RZ, -C0-4alkyl-CO2RY; and iv) one of benzimidazol-1-yl, 2,8-diazospiro[4.5]decan-1-on-8-yl, 4-{[(2-tert-butoxycarbonylaminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 4-{[(2-aminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 9-yl-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid, 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl, and where substitute HetRa is a 6-member heterocyclic ring, with a carbon atom at the bonding site and contains a >NRM group as a heteroatom, where the said heteroatom is separated from the said carbon atom at the bonding site with at least 1 additional carbon atom; Rk is chosen from a group which consists of H and -C1-4alkyl; RL is chosen from a group which consists of -CO2RS; RS is hydrogen; RM is chosen from a group which consists of RZ, -C(O)RY; RN is chosen from a group which consists of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3 and NO2; RQ is chosen from a group which consists of -CN, -C0-4alkyl-ORY, -C0-4alkyl-CO2RY, -C0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY; RW is chosen from a group which consists of RY; RX is chosen from a group which consists of -ORY, -NRYRZ, -C1-4alkyl and -C1-4alkyl-RAr; RY is chosen from a group which consists of H, C1-4alkyl, -C0-4alkyl-RAr and -C0-4alkyl-RAr', each of which is substituted with 1 or 2 RN substitutes; RZ is chosen from a group which consists of RY, -C1-2alkyl-CO2RY ; RAr is a radical with a carbon atom at the bonding position, where the said radical is chosen from a group which consists of phenyl, pyridyl and pyrazinyl, where each carbon atom with permissible valence in each of the said groups is independently substituted with at least 0, 1 or 2 RN or 0 or 1 RL; RAr' is a 5-6-member ring which has 1 or 2 heteroatoms, chosen from a group which consists of O, S, N and >NRY, and has 0 or 2 unsaturated bonds and 0 or 1 carbonyl group, where each member with permissible valence in each of the said rings is independently substituted with 0 or 1 or 2 RK; Description is given of inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), a composition which contains these inhibitions, and their use for inhibiting activity of the LTA4H enzyme, as well as for treating, preventing or suppressing inflammation and/or conditions which are associated with such inflammation. In the said formula (I): X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is chosen from a group which consists of CH2 and O, W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to a nitrogen atom; R4 is chosen from a group which consist of H, OCH3, CI, F, Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently chosen from different groups.

EFFECT: new compounds have useful biological activity.

43 cl, 8 tbl, 12 dwg, 484 ex

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