Azolopyrimidines as cannabinoid 1 receptor inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formulae Ia, Ic, Ig, Ik and pharmaceutically acceptable salts thereof, having activity towards cannabinoid 1 receptor. In formulae

, ,

, ,

R2 is selected from halogen, pyrazinyl, pyridazinyl, pyrimidinyl, pyridinyl, pyridinyl-N-oxide and phenyl; where the said pyrimidinyl, pyridinyl, pyridinyl-N-oxide, pyrazinyl and phenyl are optionally substituted with an amino group; R3 is selected from hydrogen, methylsulphonyl, methlsulphoxide and dimethylaminocarbonyl; R4 is selected from hydrogen, cyano, nitro, carbamimidoyl, tetrazolyl, aminosulphonyl, aminocarbonyl, methylsulphonylamino and methylsulphonyl; R6 is selected from hydrogen, hydroxyethylaminomethyl and methylsulphonylaminomethyl. The invention also relates to a pharmaceutical composition, methods of treating and preventing diseases mediated by the cannabinoid 1 receptor, and use of said compounds in preparing a medicinal agent used to treat such diseases.

EFFECT: improved properties of the derivatives.

12 cl, 1 tbl, 62 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from formulas Ia, Ic, Ig and Ik:


in which R2selected from halogen, pyrazinyl, pyridazinyl, pyrimidinyl, pyridinyl, pyridinyl-N-oxide and phenyl; where the specified pyrimidinyl, pyridinyl, pyridinyl-N-oxide, pyrazinyl and phenyl, R2optionally substituted amino group;
R3selected from hydrogen, methylsulfonyl, methylsulfoxide and dimethylaminoborane;
R4selected from hydrogen, cyano, nitro, carbamimidoyl, tetrazolyl, aminosulfonyl, aminocarbonyl, methylsulfonylamino and methylsulfonyl;
R6selected from hydrogen, hydroxyethylaminomethyl and methylsulfonylamino;
and their pharmaceutically acceptable salts.

2. The compound according to claim 1, selected from the following compounds: 5-[4-(2-aminopyrimidine-4-yl)phenyl]-6-(4-chlorophenyl)-3-phenyl-3,6-dihydro-[1,2,3]triazolo[4,5-d]pyrimidine-7-he; 6-[4-(6-aminopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-3-methanesulfonyl-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-[4-(6-amino-1-oxopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 2-(biphenyl-4-yl)-1-(4-chlorophenyl)-8-((2-hydroxyethylamino)methyl)-9-phenyl-1H-purine-6(N) -; 3-(6-(4-bromophenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-Piras the lo[3,4-d]pyrimidine-1-yl)benzosulfimide; 3-(6-(4-bromophenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)benzosulfimide; dimethylamide 5-[4-(6-aminopyridine-3-yl)phenyl]-6-(4-chlorophenyl)-7-oxo-3-phenyl-6,7-dihydropyrazolo[4,3-d]pyrimidine-1-carboxylic acid; 6-[4-(6-aminopyridin-3-yl)phenyl]-5-(4-chlorophenyl)-1-(3-methanesulfonyl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; N-[2-[4-(6-aminopyridine-3-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-9-phenyl-6,9-dihydro-1H-purine-8-ylmethyl]methanesulfonamide; 6-[4-(6-aminopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-3-methanesulfonyl-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-(4-(2-aminopyridine-4-yl)phenyl)-5-(4-chlorophenyl)-3-(methylsulphonyl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4(5H) -; 3-[6-(4-bromophenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]benzamide; 3-[6-[4-(6-aminopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]benzamide; 6-[4-(6-aminopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-1-(3-methanesulfonyl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-(4-chlorophenyl)-3-(3-methanesulfonyl)-5-(4-pyrazin-2-ylphenyl)-3,6-dihydro-[1,2,3]triazolo[4,5-d]pyrimidine-7-he; 5-[4-(6-aminopyridine-3-yl)phenyl]-6-(4-chlorophenyl)-3-(3-methanesulfonyl)-3,6-dihydro-[1,2,3]triazolo[4,5-d]pyrimidine-7-he; 6-[4-(5-aminopyridine-2-yl)phenyl]-5-(4-chlorophenyl)-3-methanesulfonyl-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-[4-(5-aminopyridin-2-yl)phenyl]-5-(4-chlorophenyl)-3-methanesulfonyl-1-phenyl-1,5-dihydropyrazolo[3,4-d]p is rimidine-4-one; 6-[4-(5-aminopyridine-2-yl)phenyl]-5-(4-chlorophenyl)-1-(3-methanesulfonyl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-[4-(5-aminopyridin-2-yl)phenyl]-5-(4-chlorophenyl)-1-(3-methanesulfonyl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-[4-(2-aminopyrimidine-5-yl)phenyl]-5-(4-chlorophenyl)-3-methanesulfonyl-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-[4-(2-aminopyrimidine-5-yl)phenyl]-5-(4-chlorophenyl)-1-(3-methanesulfonyl)-1,5-dihydropyrazolo-[3,4-d]pyrimidine-4-one; 3-[5-(4-chlorophenyl)-4-oxo-6-(4-pyrazin-2-ylphenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidine-1-yl]benzamide; N-{3-[2-[4-(6-aminopyridine-3-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]phenyl}methanesulfonamide; 3-[2-[4-(6-amino-pyridin-3-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]benzosulfimide; N-{3-[2-[4-(5-aminopyridine-2-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]phenyl}methanesulfonamide; 3-(6-(4-(5-aminopyridine-2-yl)phenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)benzonitrile; 3-(6-(4-(6-aminopyridine-3-yl)phenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)benzonitrile; 3-[6-[4-(6-aminopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]benzamide; 3-[6-[4-(5-aminopyridine-2-yl)phenyl]-5-(4-chlorophenyl)-4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]benzamide; 3-(2-(4-bromophenyl)-1-(4-chlorophenyl)-6-oxo-1H-purine-9(6N)-Il)benzosulfimide; 6-[4-(6-aminopyridine-3-yl)phenyl]-5-(4-chlorophenyl)-1-[3-(1H-tet the azole-5-yl)phenyl]-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 6-[4-(5-aminopyridine-2-yl)phenyl]-5-(4-chlorophenyl)-1-[3-(1H-tetrazol-5-yl)phenyl]-1,5-di-getoperator[3,4-d]pyrimidine-4-one; 2-(4-bromophenyl)-1-(4-chlorophenyl)-9-(3-(methylsulphonyl)phenyl)-1H-purine-6(N) -; N-(3-(6-(4-(6-aminopyridine-3-yl)phenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)phenyl)methanesulfonamide; 2-[4-(6-aminopyridine-3-yl)phenyl]-1-(4-chlorophenyl)-9-(3-methanesulfonyl)-1,9-dihydropyran-6-he; N-(3-(6-(4-(5-aminopyridine-2-yl)phenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)phenyl)methanesulfonamide; 2-[4-(5-aminopyridine-2-yl)-phenyl]-1-(4-chlorophenyl)-9-(3-methanesulfonyl)-1,9-dihydropyran-6-he; 6-(4-bromophenyl)-5-(4-chlorophenyl)-1-(3-nitrophenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 3-(6-(4-bromophenyl)-5-(4-chlorophenyl)-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)benzonitrile; 3-[2-[4-(5-aminopyridine-2-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]benzamide; 3-[2-[4-(5-aminopyridine-2-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-digit-ROMARIN-9-yl]benzosulfimide; 3-[2-[4-(5-aminopyridine-2-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]benzonitrile; 3-[2-[4-(6-aminopyridine-3-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]benzonitrile; N-{3-[1-(4-chlorophenyl)-6-oxo-2-(4-(pyrimidine-2-ylphenyl)-1,6-dihydropyran-9-yl]phenyl}methanesulfonamide; 1-(4-chlorophenyl)-9-(3-methanesulfonyl)-2-(4-pyrazin-2-ylphenyl)-1,9-dihydropyran-6-he; 3-[5-(4-chlorophenyl)-4-oxo-6-(4-pyrazin-2-ylphenyl)-4,5-dihydropyrazolo,4-d]pyrimidine-1-yl]benzonitrile; 3-[2-[4-(6-aminopyridine-3-yl)phenyl]-1-(4-chlorophenyl)-6-oxo-1,6-dihydropyran-9-yl]benzamide; N-(3-(5-(4-chlorophenyl)-4-oxo-6-(4-(pyrimidine-2-yl)phenyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)phenyl)methanesulfonamide; N-{3-[5-(4-chlorophenyl)-4-oxo-6-(4-pyrimidine-5-ylphenyl)-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]phenyl}methanesulfonamide; 5-(4-chlorophenyl)-1-(3-(methylsulphonyl)phenyl)-6-(4-(pyrazin-2-yl)phenyl)-1H-pyrazolo[3,4-d]pyrimidine-4(5H) -; 3-[5-(4-chlorophenyl)-4-oxo-6-(4-pyrazin-2-ylphenyl)-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]benzamide; N-(3-(5-(4-chlorophenyl)-4-oxo-6-(4-(pyridazin-3-yl)phenyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)phenyl)methanesulfonamide; N-{3-[1-(4-chlorophenyl)-6-oxo-2-(4-pyrimidine-5-ylphenyl)-1,6-dihydropyran-9-yl]phenyl}methanesulfonamide; N-(3-(5-(4-chlorophenyl)-4-oxo-6-(4-(pyrazin-2-yl)phenyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)phenyl)methanesulfonamide; N-{3-[1-(4-chlorophenyl)-6-oxo-2-(4-pyridazin-3-ylphenyl)-1,6-dihydropyran-9-yl]phenyl}methanesulfonamide; 3-(5-(4-chlorophenyl)-4-oxo-6-(4-(pyrazin-2-yl)phenyl)-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine-1-yl)benzosulfimide; N-{3-[1-(4-chlorophenyl)-6-oxo-2-(4-pyrazin-2-ylphenyl)-1,6-dihydropyran-9-yl]phenyl}methanesulfonamide; 3-[1-(4-chlorophenyl)-6-oxo-2-(4-pyrazin-2-ylphenyl)-1,6-dihydropyran-9-yl]benzosulfimide; 5-(4-chlorophenyl)-1-(3-methanesulfonyl)-6-(4-pyrimidine-5-ylphenyl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one; 5-(4-chlorophenyl)-1-(3-methanesulfonyl)-6-(4-(pyrimidine-2-Hilfe who yl)-1,5-dihydropyrazolo[3,4-d]pyrimidine-4-one and 3-[6-[4-(5-aminopyridine-2-yl)phenyl]-5-(4-chlorophenyl)-4-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidine-1-yl]benzosulfimide.

3. A method of treating diseases mediated by the cannabinoid receptor 1, including placing a therapeutically effective amount of a compound according to claim 1.

4. The method according to claim 3, where the disease is mediated via cannabinoid receptor 1 is a malnutrition associated with excessive consumption of food.

5. The method according to claim 4, where the eating disorders associated with excessive food intake, obesity is a.

6. A method of preventing the condition associated with the risk of obesity, including the introduction of compounds selected from compounds according to claim 1, in effective amounts of about 0.001 mg to about 100 mg per kg of body weight.

7. Pharmaceutical composition having activity against the cannabinoid receptor 1 (SW), including a compound selected from compounds according to claim 1, in an effective amount and a pharmaceutically acceptable carrier.

8. The use of the compounds for the manufacture of drugs useful for treating diseases mediated by the cannabinoid receptor 1, where the specified compound selected from the compound according to claim 1.

9. The use of claim 8, where the disease mediated by the cannabinoid receptor 1, selected from the group including eating disorders associated with excessive food intake, metabolic disorders, and conditions associated the metabolic disorders, including obesity, diabetes, atherosclerosis, hypertension, hypercholesterolemia, hypertriglyceridemia, cholelithiasis and gipolipidemicheskie state.

10. The use according to claim 9, where the disease is mediated via cannabinoid receptor 1 is a malnutrition associated with excessive consumption of food.

11. The use of claim 10, where the eating disorders associated with excessive food intake, obesity is a.

12. The use of compounds according to claim 1 for the manufacture of medicinal products for prophylaxis of a condition associated with the risk of obesity.



 

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11 cl, 10 ex, 2 tbl

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FIELD: chemistry.

SUBSTANCE: formula (I) compound has antibacterial activity and can be used as a medicinal agent. In formula ,

R1 is hydrogen, halogen, C1-4alkyl; R2 is selected from hydrogen, halogen, C1-4alkyl; R3 is selected from hydrogen, halogen, cyano, C1-4alkyl; W is -N(R6)-; X is a single bond; ring A is an unsaturated or partially saturated ring containing 5-6 atoms, one or two of which are independently selected from nitrogen and sulphur; or an unsaturated or partially saturated bicyclic ring containing 9-10 atoms, one, two or three of which are selected from nitrogen and sulphur; R4 and R5 are substitutes on a carbon atom and are independently selected from a halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, formyl, hydroxy iminomethyl, C1-4alkoxyminomethyl, C1-4alkyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkoxy)carbamoyl, N-(C1-4alkyl)-N-(C1-4alkoxy)carbamoyl, C1-4alkylS(O)a, where a equals 0-2, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C1-4alkylsulphonylamino, (saturated or unsaturated carbocycle containing 3-7 atoms)-R10- or (saturated, partially saturated or unsaturated ring containing 5-6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R11-; where R4 and R5 can independently and optionally substituted at the carbon atom with one or more R12; R6 is hydrogen; n equals 1-4; where values of R4 can be identical or different; m equals 0-4; where values of R5 can be identical or different; R12 is selected from azido, halogen, cyano, hydroxy, amino, carboxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkylS(O)a, where a equals 0-2, (saturated or unsaturated cabocycle containing 3-7 atoms)-R14- or (saturated, partially saturated or unsaturated ring containing 5 or 6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R15-; where R12 can independently and optionally be substituted at the carbon atom with one or more R9; R10, R11, R14 and R15 are independently selected from a single bond, -C(O)-, -N(R19)C(O)- or -C(O)N(R20)-; where R19 and R20 are independently selected from hydrogen or C1-4alkyl; R16 is selected from halogen, cyano, hydroxy, carboxy, methyl and methoxy. The invention also relates to a pharmaceutical composition, having antibacterial activity, containing the disclosed compound as an active ingredient, use of the disclosed compound to prepare a medicinal agent and a method of producing the compound of formula (I).

EFFECT: high activity of the compounds.

22 cl, 52 tbl, 721 ex

FIELD: chemistry.

SUBSTANCE: invention relates to sulphamate derivatives of benzothiophene of formula or

,

where R1, R2, R3, m and n assume values given in the claim.

EFFECT: possibility of use in treating oestrogen-dependent diseases.

38 cl, 63 ex, 10 tbl

FIELD: chemistry.

SUBSTANCE: described are novel isocyanurate derivatives (1,3,5-triazine-2,4,6-triones) of formula

, in which 1) R1=R2=CH3, X=(CH2)n (n=1-6, 10) or CH2CH(OH)CH2 or (CH2)2O(CH2)2; 2) R1=R2=CH2=CHCH2, X=CH2CH(OH)CH2; 3) R1=CH3 or C6H5CH2; R2=X-S(O)m-CH2C(O)Y, X=(CH2)2(n=1-6); in all given formulae m=1 or 2; Y=NH2 or NHNH2.

EFFECT: high antituberculosis activity, as well as towards multi-drug resistant mycobacteria strains, high species specificity and low toxicity.

2 cl, 5 tbl, 115 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the formula I

, where: m equals 0, 1 or 2, where if m=0, disappears such that an open ring or single bond forms, n equals 0, 1 or 2, wherein when n=0, disappears such that an open ring or single bond forms; m' and n' are independently equal to 0, 1 or 2; X denotes a carbon atom; Y denotes a carbon or sulphur atom; provided that m and n are not equal to 0 at the same time; denotes a single or double bond, if needed; --- absence of a bond or a single bond, if needed; R1 is selected from a group comprising CN, Hal, OAIk, OH, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', (Alk)p-C(O)NRR', piperidine, wherein Alk is optionally substituted with Hal or OAlk, where p=0 or 1; R3, R4, R5 and R6 are identical or different and are independently selected from a group comprising H, OAIk, Alk, Hal, OH; R2 is selected from a group comprising H and O, and p'=0 or 1; R7 is selected from a group comprising H, O, OH, N-OH, N-aryl, N-OAlk, N-O-aryl, N-O-Alk-aryl, N-NR-CONRR', N-O-CO-Alk, or 2 R7, bonded with the same Y, together form lioksalan; wherein said Alk is optionally substituted with OAlk, -CO-(NR-Alk-CO)p'-OAlk, and p'=0 or 1; R and R', which are identical or different, are independently selected from a group comprising H, and Alk; or pharmaceutically acceptable salt or optical isomer or diastereomer thereof, except those compounds for which: R3, R4, R5, R6=H, R1=CN, denotes a single bond, and denotes -C(=N-(2,4,6-trimethylphenyl))-, -C(=N-(2,6- dimethylphenyl))-, -C(=N-(2,6-diethylphenyl))-, -C(=N(2-methylphenyl))-, -C(=N(2-ethylphenyl))-, -C(=N-(2-trifluoromethylphenyl))-, -C(=N-(2-isopropylphenyl))-, -C(=N-phenyl)-, -C(=N-(naphthyl)- or -C(=O)-, -CH2-, or R3, R5, R6=H, R4=OMe, R1=CN, denotes a single bond, and denotes -C(=O)-, or R3, R4, R5, R6=H, R1=NH2, denotes a single bond, and denotes -CH2- or -CH2-CH2-; or R3, R4, R5, R6=H, R,=NH2, denotes -CH2- or -CH2-CH2-, and denotes a single bond. The invention also relates to a cysteine protease based pharmaceutical composition based on compounds of formula I, use of the compound of formula I to prepare a drug for inhibiting cysteine protease, for treating and preventing cancer, as well as inflammatory diseases and others.

EFFECT: novel compounds which can be used in medicine are obtained and described.

38 cl, 43 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the formula I

, where: m equals 0, 1 or 2, where if m=0, disappears such that an open ring or single bond forms, n equals 0, 1 or 2, wherein when n=0, disappears such that an open ring or single bond forms; m' and n' are independently equal to 0, 1 or 2; X denotes a carbon atom; Y denotes a carbon or sulphur atom; provided that m and n are not equal to 0 at the same time; denotes a single or double bond, if needed; --- absence of a bond or a single bond, if needed; R1 is selected from a group comprising CN, Hal, OAIk, OH, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', (Alk)p-C(O)NRR', piperidine, wherein Alk is optionally substituted with Hal or OAlk, where p=0 or 1; R3, R4, R5 and R6 are identical or different and are independently selected from a group comprising H, OAIk, Alk, Hal, OH; R2 is selected from a group comprising H and O, and p'=0 or 1; R7 is selected from a group comprising H, O, OH, N-OH, N-aryl, N-OAlk, N-O-aryl, N-O-Alk-aryl, N-NR-CONRR', N-O-CO-Alk, or 2 R7, bonded with the same Y, together form lioksalan; wherein said Alk is optionally substituted with OAlk, -CO-(NR-Alk-CO)p'-OAlk, and p'=0 or 1; R and R', which are identical or different, are independently selected from a group comprising H, and Alk; or pharmaceutically acceptable salt or optical isomer or diastereomer thereof, except those compounds for which: R3, R4, R5, R6=H, R1=CN, denotes a single bond, and denotes -C(=N-(2,4,6-trimethylphenyl))-, -C(=N-(2,6- dimethylphenyl))-, -C(=N-(2,6-diethylphenyl))-, -C(=N(2-methylphenyl))-, -C(=N(2-ethylphenyl))-, -C(=N-(2-trifluoromethylphenyl))-, -C(=N-(2-isopropylphenyl))-, -C(=N-phenyl)-, -C(=N-(naphthyl)- or -C(=O)-, -CH2-, or R3, R5, R6=H, R4=OMe, R1=CN, denotes a single bond, and denotes -C(=O)-, or R3, R4, R5, R6=H, R1=NH2, denotes a single bond, and denotes -CH2- or -CH2-CH2-; or R3, R4, R5, R6=H, R,=NH2, denotes -CH2- or -CH2-CH2-, and denotes a single bond. The invention also relates to a cysteine protease based pharmaceutical composition based on compounds of formula I, use of the compound of formula I to prepare a drug for inhibiting cysteine protease, for treating and preventing cancer, as well as inflammatory diseases and others.

EFFECT: novel compounds which can be used in medicine are obtained and described.

38 cl, 43 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzimidazole derivatives of formula

and pharmaceutically acceptable salts and esters thereof, where R1 denotes C1-10alkyl, lower alkoxy group-lower alkyl, lower alkoxy group-carbonyl-lower alkyl, C3-6cycloalkyl, C3-6cycloalkyl-lower alkyl, phenyl, phenyl-lower alkyl, di(phenyl)-lower alkyl, heterocyclyl, such as piperidinyl, tetrahydropyranyl, 2-oxo-pyrrolidinyl-lower alkyl, where the cycloalkyl, phenyl or heterocyclyl group is optionally substituted with 1-2 substitutes independently selected from a group comprising lower alkyl, lower alkoxy group, lower alkoxy group-carbonyl, morpholinyl, formylamino group and halogen; R2 denotes hydrogen or lower alkyl; R3 denotes lower alkyl, C3-6cycloalkyl, partially unsaturated cyclohexyl, phenyl, phenyl-lower alkyl, pyridinyl, benzodioxolyl, tetrahydropyranyl, where the phenyl group is optionally substituted with 1-2 substitutes independently selected from a group comprising a halogen, lower alkyl, lower alkoxy group, fluoro-lower alkyl, fluoro-lower alkoxy group, N(lower alkyl)2; R4 denotes: a) heteroaryl which is an aromatic 5-6-member monocyclic ring or a 9-10-member bicyclic ring containing 1 or 2 heteroatoms selected from nitrogen, oxygen and/or sulphur, which is optionally substituted with 1-2 substitutes independently selected from a group comprising lower alkyl, phenyl, lower alkoxy group, -N(lower alkyl)2, oxo group, NH2, halogen, cyano group and morpholinyl; b) unsubstituted naphthyl, naphthyl or phenyl, which are substituted with 1-3 substitutes independently selected from a group comprising halogen, hydroxy group, NH2, CN, hydroxy-lower alkyl, lower alkoxy group, lower alkyl-carbonyl, lower alkoxy group-carbonyl, sulphamoyl, di-lower alkyl-sulphamoyl, lower alkyl-sulphonyl, thiophenyl, pyrazolyl, thiadiazolyl, imidazolyl, triazolyl, tetrazolyl, 2-oxopyrrolidinyl, lower alkyl, fluoro-lower alkyl, fluoro-lower alkoxy group, N(lower alkyl)2, carbamoyl, lower alkenyl, benzoyl, phenoxy group and phenyl which is optionally substituted with 1-2 substitutes independently selected from halogen and fluoro-lower alkyl; or c) if R3 denotes cycloalkyl and R1 denotes cycloalkyl, then R4 can also denote phenyl; R5, R6, R7 and R8 independently denote H, halogen, lower alkoxy group or lower alkyl, or R6 and R7, which are bonded to each other, form a 6-member aromatic carbocyclic ring together with carbon atoms to which they are bonded; provided that the compound of formula (I) is not selected from a group comprising butylamide 2-[2-(2-chlorophenyl)benzoimidazol-1-yl]-4-methylpentanoic acid and 2-(2-benzo[1,3]dioxol-5-ylbenzoimidazol-1-yl)-N-benzyl-butyric acid amide. The invention also relates to a pharmaceutical composition based on the formula I compound.

EFFECT: novel benzimidazole derivatives which are useful as farnesoid X receptor antagonists are obtained.

30 cl, 379 ex

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