Pyrazoles

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), where one of R1 and R2 is hydrogen or alkyl, and the other is (CH2)PY, where p=0 or 1, Y is a saturated mono-, bi- or tricyclic 5-10-member cycloalkyl ring optionally substituted with alkyl, or R1 and R2 together with N form a 7-10-member saturated bicyclic ring Z, optionally substituted with halogen, or a 5-7-member monocyclic ring Z, optionally substituted with alkyl, phenyl, phenylalkyl or pyridinyl; R3 is [2,2']bithiophenyl, 1-methylindole, 2,3-dihydrobenzo[1,4]dioxin, benzo[1,3]dioxole, benzothiophene, dibenzofuran, furan, naphthalene, quinoline, thianthrene, thiophene or pyrrole, or biphenyl substituted with halogen, or phenyl optionally substituted with one or more amino, cyano, formyls, halogens, hydroxyl, hydroxymethyls, acyls, acylamino, alkoxy, nitro, trifluoromethoxy, trifluoromethyls, phenoxy or benzyloxy, or R3 is a group, where Ar is phenyl substituted with halogen; and R4 is alkyl; and pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition with inhibitory activity towards the 11β-hydroxysteroid dehydrogenase1 (11(β-HSD1) enzyme.

EFFECT: pyrazole composition is disclosed.

22 cl, 1 tbl, 116 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula I:

where one of R1or R2represents hydrogen or alkyl and the other is -(CH2)pY, where p denotes 0 or 1 and Y represents a saturated mono-, bi - or tricyclic 5-to 10-membered cycloalkyl ring, optionally substituted lower alkyl,
or R1and R2together with the N atom to which they are attached, form a substituted or unsubstituted ring Z, where Z represents the t a 7-10-membered bicyclic saturated ring, optionally substituted with halogen, or a 5-7 membered monocyclic ring, optionally substituted lower alkyl, phenyl, phenyl-lower alkyl or pyridinyl;
R3represents an aromatic cyclic system selected from the group consisting of [2,2']bithiophene, 1-methylindole, 2,3-dihydrobenzo[1,4]dioxin, benzo[1,3]dioxole, benzothiophene, dibenzofuran, furan, naphtalene, quinoline, thianthrene, thiophene and pyrrole, and biphenyl, substituted with halogen, and phenyl, where the aforementioned phenyl ring may be unsubstituted or substituted by one or more amino, cyano, formulae, halogen, hydroxy, hydroxymethylene, lower atilov, lower acylamino, lower alkoxy, lower alkoxycarbonyl, 2-(lower alkoxycarbonyl)attilli, lower alkilani, lower alkylthio, nitro, triptoreline, triptoreline, phenoxy or benzyloxy,
or R3is:

where Ar represents phenyl, substituted with halogen; and
R4represents lower alkyl;
and its pharmaceutically acceptable salts.

2. The compound according to claim 1, where R1represents hydrogen and R2represents a substituted 6-8-membered cycloalkyl ring.

3. The compound according to claim 1, where R2represents 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl, 2,6,6-crimetime is yclo[3.1.1]hept-3-yl, 3-lordamantr, adamantane-1-yl, adamantane-1-ylmethyl, adamantane-2-yl, 1,2,3,4-tetrahydronaphthyl, cyclohexyl, cyclooctyl or cycloheptyl.

4. The compound according to claim 1, where Z is a 5-7-membered monocyclic ring, substituted lower alkyl, phenyl-lower alkyl or pyridinyl.

5. The compound according to claim 1 where Z is selected from the group consisting of 2-ethylpiperidine, 3-phenylpyrrolidine, 3-(pyridin-3-yl)pyrrolidine, 4-hardcoresexonline, 4A-brendacarolina, 6-bromochloroethane, 3-benzylpiperidine, decahydroquinoline and decahydroquinoline.

6. The compound according to claim 1, where R3is benzothiophen or phenyl.

7. The connection according to claim 6, where the phenyl as R3substituted by one or more halogen, lower alkoxy or lower alkilani.

8. The compound according to claim 1, selected from the group consisting of the following compounds:
(3-cyclohexylpiperidine-1-yl)-(1-methyl-5-phenyl-1H-pyrazole-4-yl)methanon,
(1-methyl-5-phenyl-1H-pyrazole-4-yl)-(TRANS-octahydronaphthalene-2-yl)methanon,
(3-benzylpiperidine-1-yl)-(1-methyl-5-phenyl-1H-pyrazole-4-yl)methanon,
(1-methyl-5-phenyl-1H-pyrazole-4-yl)-(3-phenylpyrrolidine-1-yl)methanon,
(1-methyl-5-phenyl-1H-pyrazole-4-yl)-(3-pyridin-3-iparralde-1-yl)methanon,
(1-methyl-5-phenyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-methyl-5-m-tolyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-m is Tyl-5-p-tolyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
3-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]benzonitrile,
4-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]benzonitrile,
[5-(4-isopropylphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-isopropylphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-tert-butylphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(1-methyl-1H-indol-5-yl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
(5-biphenyl-4-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(5-biphenyl-3-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-methyl-5-naphthalen-1-yl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-methyl-5-quinoline-5-yl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-methyl-5-quinoline-3-yl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
4-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]benzaldehyde,
3-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]benzaldehyde,
1-{4-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]phenyl}Etalon,
1-{3-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]phenyl}Etalon,
[5-(3-AMINOPHENYL)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
N - {4-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]phenyl}acetamide", she
(1-methyl-5-thiophene-3-yl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(5-[2,2']bithiophene-5-yl-1-m is Teal-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(5-furan-3-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(5-benzo[b]thiophene-2-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(5-benzo[b]thiophene-3-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-methyl-5-Centren-1-yl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
[1-methyl-5-(3-methylsulfinylphenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(4-methylsulfinylphenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(2-methylsulfinylphenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
{5-[(E)-2-(4-chlorophenyl)vinyl]-1-methyl-1H-pyrazole-4-yl}-(octahedrally-1-yl)methanon,
(4-characterizaion-1-yl)-(1-methyl-5-phenyl-1H-pyrazole-4-yl)methanon,
[5-(4-chlorophenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chlorophenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-4-forfinal)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(5-chloro-2,4-differenl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(2-forbiden-4-yl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-amino-4-chlorophenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(2-chloro-4-were)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(5-chloro-2-were)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-4-were)-1-methyl-H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-2-were)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-chloro-3-were)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-chloro-2-were)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(3-triptoreline)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(4-triptoreline)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(2-fluoro-5-triptoreline)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-4-triptoreline)-1-methyl-1H-pyrazole-4-yl] -(octahedrally-1-yl)methanon,
(4A-bromochlorophenol-2-yl)-(1-methyl-5-phenyl-1H-pyrazole-4-yl)methanon,
[1-methyl-5-(3-nitrophenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(4-nitrophenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
methyl ester of 3-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]benzoic acid
methyl ester 4-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]benzoic acid
methyl ester (E)-3-{4-[2-methyl-4-(octahedrally-1-carbonyl)-2H-pyrazole-3-yl]phenyl}acrylic acid,
[5-(3-hydroxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
(5-dibenzofuran-4-yl-1-methyl-1H-Piras the l-4-yl)-(octahedrally-1-yl)methanon,
[1-methyl-5-(4-phenoxyphenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(2-phenoxyphenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3,4-acid)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(2,3,4-trimethoxyphenyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-hydroxymethylene)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-benzyloxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-benzyloxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(6-ethoxynaphthalene-2-yl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
(5-benzo[1,3]dioxol-5-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
[1-methyl-5-(4-trifloromethyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(3-trifloromethyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[1-methyl-5-(2-trifloromethyl)-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-chloro-2-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-4-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(2-chloro-4-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(5-fluoro-2-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(OCTA is hydrochinon-1-yl)methanon,
[5-(2-fluoro-3-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-benzyloxy-3-chlorophenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(2-chloro-4-ethoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-4-ethoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(4-chloro-2-ethoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
[5-(3-chloro-4-propoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon,
(adamantane-1-ylmethyl)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
adamantane-1-alamid 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
hexahydro-2,5-methanoindan-3A(1H)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
cycloheptylamine 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
(1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-yl)-(3-phenylpyrrolidine-1-yl)methanon,
(1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon,
(1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-yl)-(4R,8S)-octahydronaphthalene-2-ylmethanol,
(6-bromochlorophenol-2-yl)-(1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-yl)methanon,
cyclooctylamine 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid is,
adamantane-2-alamid 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
(adamantane-1-ylmethyl)amide 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
adamantane-1-alamid 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)amide 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
((1R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)amide 1-methyl-5-pyrrol-1-yl-1 H-pyrazole-4-carboxylic acid,
((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)amide 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)amide 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
(1,2,3,4-tetrahydronaphthalen-1-yl)amide 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
cyclohexylamin 1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-carboxylic acid,
(3-benzylpiperidine-1-yl)-(1-methyl-5-pyrrol-1-yl-1H-pyrazole-4-yl)methanon,
(2-ethylpiperidine-1-yl)-(1-methyl-5-phenyl-1H-pyrazole-4-yl)methanon,
methyl-((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid and
adamantane-2-isopropylamino 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid,
and their pharmaceutically acceptable salts.

9. The compound according to claim 1, where the specified connection is represented by (1-methyl-5-phenyl-1H-pyrazole-4-yl)-(TRANS-octahydronaphthalene-2-yl)methanon.

10. The compound according to claim 1, where the specified connection is made the focus of a [5-(4-isopropylphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon.

11. The compound according to claim 1, where the specified connection is a (5-benzo[b]thiophene-2-yl-1-methyl-1H-pyrazole-4-yl)-(octahedrally-1-yl)methanon.

12. The compound according to claim 1, where the specified connection represents [5-(2-chloro-4-were)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon.

13. The compound according to claim 1, where the specified connection represents [5-(2-chloro-4-methoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon.

14. The compound according to claim 1, where the specified connection represents [5-(2-chloro-4-ethoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon.

15. The compound according to claim 1, where the specified connection represents [5-(3-chloro-4-ethoxyphenyl)-1-methyl-1H-pyrazole-4-yl]-(octahedrally-1-yl)methanon.

16. The compound according to claim 1, where the specified connection is a (adamantane-1-ylmethyl)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid.

17. The compound according to claim 1, where the specified connection is an adamantane-1-alamid 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid.

18. The compound according to claim 1, where the specified connection is a ((1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl)amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic acid.

19. The compound according to claim 1, where the specified connection is a ((1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl) amide 1-methyl-5-phenyl-1H-pyrazole-4-carboxylic sour the s.

20. Pharmaceutical composition having inhibitory activity against the enzyme 11β-hydroxysteroiddehydrogenase (11β-HSD1), which contains the compound according to any one of claims 1 to 19 in an effective amount and a pharmaceutically acceptable carrier and/or adjuvant.

21. Compounds according to any one of claims 1 to 19, having inhibitory activity against the enzyme 11β-hydroxysteroiddehydrogenase (11β-HSD1).

22. Compounds according to any one of claims 1 to 19 for use as therapeutically active substances for the treatment and/or prevention of diseases which are modulated by inhibitors of 11β-hydroxysteroiddehydrogenase.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrrolidine-3,4-dicarboxamide derivatives of formula (I): , where: X is N or C-R6; R1 is C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7alkyl, fluoro-C1-7alkyl, hydroxy-C1-7alkyl, CN-C1-7alkyl, R10C(O), R10OC(O)-, N(R11,R12)C(O)-; R10OC(O)C1-7alkyl, N(R11,R12)C(O)-C1-7alkyl, R10SO2, R10-SO2-C1-7alkyl, N(R11, R12)-SO2, N(R11,R12)-SO2-C1-7alkyl, aryl-C1-7alkyl, 5-member monocyclic heteroaryl containing a nitrogen atom, where the ring carbon atom can be substituted with a carbonyl group, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents an aromatic -member monocyclic ring with 1 S atom or a 6-member monocyclic ring with 1 N atom, C1-7alkoxy-C1-7alkyl, C1-7alkoxycarbonyl-C3-10cycloalkyl-C1-7alkyl or halogen substituted 4-member heterocyclyl-C1-7alkyl with one O atom; R2 is H, C1-7alkyl; R3 is aryl, aryl-C1-7alkyl, heteroaryl, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents a 5-member monocyclic ring with 1 S atom, a 6-member monocyclic ring with 1 or 2 N atoms, 9-, 10-member bicyclic system with 1 or 2 N atoms in one ring; R4 is H, C1-7alkyl, OH; R5, R6, R7, R8 are independently selected from a group consisting of H, halogen, C1-7alkyl, C1-7alkoxy, flouro-C1-7alkyl, fluoro-C1-7alkyloxy; R9 is aryl, heterocyclyl, heteroaryl, heterocyclyl-C(O)-; R10 is H, C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7alkyl, fluro-C1-7alkyl, heteroaryl, heteroaryl-C1-7alkyl, where the term "heteroaryl" represents a 5-member monocyclic ring with 4 N atoms, a 5-member heterocyclyl with 1 N atom; R11, R12 are independently selected from a group consisting of H, C1-7alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-7 alkyl; and pharmaceutically acceptable salts thereof; where the term "aryl" represents a phenyl group which can be optionally substituted with 1 to 5 substitutes which are independently selected from a group consisting of the following: halogen, CF3, NH2, C1-7alkylsulphonyl, C1-7alkoxy, fluoro-C1-7alkyl, fluoro-C1-7 alkoxy; the term "heterocyclyl" represents a nonaromatic monocyclic 5-, 6-member heterocyclic group with 1, 2 N atoms, or with 1 N atom and 1 O atom, where the heterocyclyl group can be substituted as indicated with respect to the term "aryl", and one carbon atom of the ring system of the heterocyclyl group can be substituted with a carbonyl group; the term "heteraryl" represents an aromatic 5- or 6-member monocyclic ring system which can have 1, 2, 3 N atoms, or 1 N atom and 1 S atom, where the heteroaryl group can be substituted as indicated with respect to the term "aryl", and one carbon atom of the ring system of the heteroaryl group can be substituted with a carbonyl group. Formula I compounds have inhibitory activity towards coagulation factor Xa.

EFFECT: possibility of using said compounds in a pharmaceutical composition and for preparing a medicinal agent.

27 cl, 90 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing new 3,4-dithienyl-substituted maleic anhydrides or maleimides of general formula I: , where X=O, or NR1; R1 and R2=alkyl C1-C4; R3=alkyl C1-C4, or nitrogen- and/or sulphur-containing heterocyclic substitute. The method involves reacting the corresponding 2,5-disubstituted 3-thienyl-acetic acid with the corresponding 2,5-disubstituted 3-halogen acetythiophenes while heating in the presence of a base in a medium of inert organic solvent in atmospheric oxygen with subsequent separation of the end product of general formula I, where X=O, or, if necessary, the latter is converted to a compound of general formula I, where X=NR1, where R1 assumes values given above, by treating it with the corresponding amine. These compounds can be used as photochromes, which are widely used as optical switches in high-capacity data carriers used for recording, processing and storing data.

EFFECT: versatility of the method, ie possibility of obtaining compounds with and without equivalent heterocyclic substitutes using readily available thienyl-acetic acid and halogen ketones of the thiophene family, which considerably widens the assortment of organic photochromic dithienylethenes.

4 cl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention is related to compound represented by formula (1) , in formula A represents nitrogen-containing saturated ring; m represents integer number, equal to 0, 1 or 2; n represents integer number, equal to 1, 2, 3 or 4; G1 represents atom of hydrogen, hydroxyl group or alkoxygroup; G2 represents atom of halogen, hydroxyl group, cyanogroup, alkyl group, alkenyl group, alkinyl group, which may be substituted with hydroxyalkyl group, alkoxygroup, alkyl thiogroup, aminogroup or aryl group; G3 represents atom of hydrogen; G4 represents hydroxyl group or -N(R1)(R2) (R1 and R2 may be identical or different, and independently represent atom of hydrogen, alkyl group, aralkyl group, alkenyl group or saturated heterocyclic group); and G5 represents substituent at carbonic atom, which constitutes nitrogen-containing saturated ring, represented with A, and represents atom of hydrogen, to medicinal agent on the basis of this compound for treatment and prophylaxis of glaucoma, to inhibitor of phosphorylation of regulatory light chain of myosin and inhibitor of kinase Rho/Rho path, and also to method of therapeutical and/or prophylactic treatment of glaucoma.

EFFECT: new compounds have been produced and described, which efficiently inhibit phosphorylation of regulatory light chain of myosin.

32 cl, 42 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention is related to compound of formula (I) , where

R1 -C1-8alkyl; R2 - pyridynyl, unnecessarily substituted with C1-8alkyl, quinolyl or isoquinolyl; R3 - hydrogen or C1-8alkylcarbonyl; R4 means group of formula G-L1-(CRR')n-, in which n is integer number from 0 to 3; R and R' are independently selected from group that includes atoms of hydrogen and lower alkyl groups; L1 means connection group, selected from group, which includes direct connection, groups -O-, -CO-, -NR"-, -O(CO)O-, -O-(CO)-, -(CO)O- and -NR"-(CO)-, where R" is lower alkyl; G is selected from group, including atoms of hydrogen, C1-8alkyl, C2-8alkenyl, C3-7dicloalkyl, phenylC1-8alkyl, pyridinyl, thiophenyl or residue of indan, and also phenyl, unnecessarily substituted with atom of halogen, C1-8alkoxy, cyano- or C1-8alkyl, which, in its turn, unnecessarily contains one or more atoms of halogen. Specified compounds are active and selective inhibitors of phosphodiesterase 4 (FDE4), therefore, they are applicable for treatment, prevention or suppression of pathological conditions, diseases or disorders, for which it is known that their behavior is relieved by inhibition of FDE4, such as asthma, chronic obstructive lung disease, rheumatoid arthritis, atopic dermatitis, psoriasis or syndrome of sore large gut. Invention is related also to pharmaceutical compositions on the basis of mentioned compounds, application of compounds, method for treatment of subject, when efficient amount of specified compounds is introduced to them. Besides invention is related to combined product for treatment or prevention of pathological condition or disease, behavior of which is relieved by inhibition of phosphodiesterase 4, including specified compound and another compound, selected from the group that includes (a) steroids, (b) immunosuppressive agents, (c) blockers of T-cells receptors, (d) anti-inflammatory medicinal agents, (e) β2-adrenergic agonists and (f) antagonists of muscarine receptors M3, for single-time, separate or serial use.

EFFECT: improved efficiency of compounds use.

11 cl, 2 tbl, 77 ex

FIELD: medicine.

SUBSTANCE: invention refers to imidazole derivatives of formula (1a): and/or to stereoisomeric forms of compound of formula (1a) and/or to physiologically acceptable salt of compound of formula (1a), and U means 1) hydrogen atom; X means the remaining formula (II): -(A1)m-A2 (II), where m means an integer 1; A1 means 1) -(CH2)n- where n means an integer 1; A2 means 1) aminopyridyl; Y means 1) the remaining formula (III): A3-(A4)o-(A5)p (III), and A3 means (C3-C8)-cycloalkyl or (C2-C6)-alkinylene wherein cycloalkyl or alkinylene is unsubstituted or independently one-, two- or three-substituted with R1, A4 is absent, A5 is absent; b) A3 means -(C3-C8)-cycloalkyl wherein cycloalkyl is unsubstituted or independently one-, two- or three-substituted with R1, A4 means -N(R2)- and A5 means a)1) -C(O)-R3; a)2) -C(O)-N(R4)-R5; a)3) -(SO2)-R6; O stands for an integer 1, and p stands for an integer 1; A3 means cyclic amine with 3-8 atoms in cycle where cyclic amine is unsubstituted, A4 is absent; and A5 has value specified in cl. b), and A5 is connected with N-atom A3, o means an integer zero and p means an integer zero or 1; or d) A3 means -(CH2)q-phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted with R1, A4 is absent; and A5 has value specified in cl. b), p means an integer 1 and q means integer zero or 1;) A3 means -(CH2)rHet wherein Het stands for benzothiophene or piperidine which is unsubstituted or independently one-, two- or three-substituted by =0 or R1, A4 is absent; and A5 has value specified cl. b), p means an integer 1 and r means an integer 1 or 2; f) A3 means -(CH2)q-phenyl wherein phenyl is unsubstituted, A4 means -O- A5 means phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted by R1, o and p mean an integer 1, and q means an integer zero, 1; g) -CH(-phenyl)-phenyl; and R1 means phenyl, and phenyl is unsubstituted or independently one-, two- or three-substituted by -(C1-C6)alkyl, b) triazolyl,) c) - (C1-C6)-alkyl, d) - (C0-C4)-alkyl - (C3-C8) a-cycloalkyl, e) -O-CF3 or g) halogen; and R2 means: a) hydrogen atom; and R3 and R6 are identical or different and independently mean: a) -(C1-C6)-alkyl wherein alkyl is unsubstituted or independently one-, two- or three-substituted by R1, b) -phenyl wherein phenyl is unsubstituted or independently one-, two- or three-substituted by R1, while R4 and R5 are identical or different and independently mean: a) -(C1-C6)-alkyl or -(C2-C10)-alkenyl wherein alkyl or alkenyl is unsubstituted, b) -phenyl wherein phenyl is unsubstituted, c) hydrogen atom; Y means 2) the remaining formula (IV): , and R8 means a) -phenyl where phenyl is unsubstituted; Z means 1) hydrogen atom, 2) -(C1-C6)-alkyl, 3) -(C1-C6)-alkyl, 4) -(C0-C4)-alkyl-(C3-C6)-cycloalkyl, 5) -(C1-C10)-alkyl-O-C(O)-O-R1. Besides the invention concerns the method for making the compound of formula (1a) and the based medicinal agent for inhibition of TAFIa enzyme.

EFFECT: production of new compounds and the based medicinal agent to be used in medicine to prevent and treat the conditions accompanied with thromboses, embolism, hypercoagulation or fibrotic changes.

8 cl, 1 tbl, 47 ex

Amide derivatives // 2375352

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I, to its pharmaceutically acceptable salts exhibiting properties of inhibitors of cytokine production, such as TNF (tumour necrosis factor) and various members of interleukins (IL) family, and properties of kinase inhibitors, particularly p38α kinase. The invention also concerns methods for producing; pharmaceutical compositions and application thereof for making the medicines for treating diseases affected by the compound of the invention with specified activity. In formula I , m represents 0, 1 or 2; R1 represents halogeno, hydroxy, (1-6C) alkyl, (1-6C)alkoxy, (2-6C)alkenyl, (2-6C) alkinyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, amino-(2-6C) alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, N-(1-6C)alkylcarbamoyl - (1-6C)alkoxy, di[(1-6C) alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy and wherein any heteroaryl or heterocyclyl group in substitute representing R1, can probably have 1 or 2 substitutes chosen from hydroxy, halogeno, (1-6C) alkyl, (2-6C)alkinyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxycarbonyl, (2-6C) alkanoyl, halogen-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, carboxy- (1-6C)alkyl and methylsulphonyl and wherein any said substitute representing R1 which contains group CH2 attached to 2 carbon atoms, or group CH3 attached to carbon or nitrogen atom, can probably have with each specified group CH2 or CH3, one or two substitutes chosen from halogeno, hydroxy, amino, triflouromethyl, oxo, carboxy, acetamido, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkyamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, halogen-(1-6C)alkyl, (1-6C)alkoxycarbonyl, carbamoyl, N, N-di-[(1-6)alkyl]carbamoyl, (1-6C)alkylsulphonyl, heteroaryl, heteroaryl-(1-6)alkyl and heterocyclyloxy and wherein any heterocyclyl group in substitute representing R1, can probably have 1 oxo-subsitute; R2 represents trifluoromethyl or (1-6C)alkyl; R3 represents hydrogen or (1-6C)alkyl; and R4 represents (3-6C)cycloalkyl, and R4 can be optionally substituted with one or more substitutes chosen from (1-6C)alkyl; and wherein heteroaryl represents aromatic 5- or 6-merous monocyclic ring containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur; heterocyclyl represents saturated 3-10-merous monocyclic or bicyclic ring, each containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur.

EFFECT: improved efficiency.

24 cl, 16 tbl, 66 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treatment and prevention of diseases associated with activity of specified enzyme, such as diabetes, obesity, diseases associated with food intake, dyslipidemia and hypertension. In general formula (I) , R1 represents methyl, ethyl, cyclopropyl, cyclobutyl, isopropyl, tert-butyl, methoxymethyl, cyclopropyl methoxymethyl, 2-methyl thiazolyl, morpholinyl methyl or phenyl; R2 represents hydrogen, C1-4alkyl or phenyl; R3 represents hydrogen, C1-4alkyl or phenyl; R4 represents phenyl, naphthyl, thiophenyl, quinolyl or piperidyl where phenyl, naphthyl, thiophenyl, quinolyl and piperidyl are optionally substituted with one to three substitutes independently chosen of C1-4alkyl, halogen, C1-4alkoxy, cyano, trifluoromethyl, phenyl, phenyls C1-4alkyl, phenyloxy, oxasolyl and pyridinyl; R5 represents hydrogen, C1-4alkyl, phenyl-C1-4alkyl, C3-6dicloalkyl-C1-4alkyl or aminocarbonylC1-4alkyl.

EFFECT: higher clinical effectiveness.

17 cl, 2 dwg, 72 ex

FIELD: chemistry.

SUBSTANCE: invention refers to the new compounds of general formula (II) , whereat values R1, R2, X, R11, R12, R18, R19, m, n are displayed in claim 1 of the formula.

EFFECT: compounds display agonistic and antagonistic activity which allows to propose their usage in pharmaceutical compositions for treatment of diseases and distresses connected with histamine H3 receptor.

38 cl, 80 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the aminopyridin compound of general formula (I) or its salt wherein X1, X2, X3, Z, Y1, Y2 are carbon or nitrogen atom, R, R1, R5, R6 are hydrogen atom, alkyl group, further see formula of the invention, and R7 is hydrogen or halogen atom, nitro or cyano group, -CpH2(p-1)(Ra1)(Ra2)-O-Ra3, -C(=O)-Rd1, 5-or 6-membered saturated heterocycle group, aromatic heterocycle group, -N(Rh1)(Rh2), further see formula of the invention. The invention refers also to the pharmaceutic composition thereof intended for treatment or prevention of allergic diseases, autoimmune diseases caused by malignant tumour, to the Syk inhibitor containing the compound of formula I and to the therapeutic and/or preventive agent.

EFFECT: compounds which not only possess high Syk inhibition activity but are selective Syk inhibitors are obtained and described.

24 cl, 24 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: in formula I X is C-R6 or N, R1 is hydrogen, R2 is selected from a group comprising (lower)alkyl unsubstituted or substituted with one, two or three substitutes, independently selected from a group comprising hydroxy, (lower)alkoxy, fluoro(lower)alkyl, phenyl, C3-8cycloalkyl and a 6-member saturated heterocyclic ring containing two heteroatoms selected from nitrogen and oxygen atoms, C3-8cycloalkyl, unsubstituted or substituted hydroxyl, 5- or 6-member saturated heterocyclic ring containing one nitrogen atoms, where the said heterocyclic ring is unsubstituted or substituted hydroxy, fluoro(lower)alkyl, bicyclo[4.1.0]hept-7-yl, unsubstituted or condensed with a phenyl ring; and 4,7,7-trimethylbicyclo[2.2.1]hept-2-yl, substituted with one substituted independently selected from a group comprising hydroxy, (lower)alkoxy and (lower)acyloxy, R3 is a 5- or 6-member saturated heterocyclic ring containing one or two oxygen atoms, where the said heterocyclic ring is unsubstituted or substituted with one or two substitutes independently selected from a group comprising (lower)alkyl and alkoxycarbonyl, or condensed with a phenyl ring, or R2 is a pyrrolidine ring which is unsubstituted or substituted with (lower)alkyl and alkoxycarbonyl. Values of the rest of the radicals are given in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound as an active ingredient.

EFFECT: disclosed compounds have antagonistic activity towards cannabinoid receptors CB1 and can be used as therapeutically active substance for preparing medicinal agents with antagonistic activity towards cannabinoid receptors CB1.

20 cl, 74 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of aminobenzimidazole and benzimidazole of general formula (I-b-1), additive salt or stereochemically isomeric form thereof, where G is a single bond or C1-10alkanediyl; R1 is halogenphenyl, pyridyl, pyrazinyl, quinolinyl, benzimidazoly or a radical of formula (c-4), where each of the said monocyclic or bicyclic heterorings can be optionally substituted with 1, 2 or 3 substitutes, independently selected from a group consisting of halogen, hydroxy, C1-6alkyl, C1-6alkyloxy, Ar1C1-6alkyloxy, C1-6alkyloxy-CH2-CH2-O-; m equals 2; Q is hydrogen, amino or mono(C1-4alkyl)amino; R3b is hydrogen or C1-6alkyl; R4a is selected from a group of substitutes consisting of hydrogen, Ar2C1-6alkyl, Het- C1-6alkyl, hydroxy C1-6alkyl, (hydroxyC1-6alkyl)oxy C1-6alkyl, C1-6alkyl, (Ar1C1-6alkyloxy)(hydroxy)C1-6alkyl, aminoC1-6alkyl, mono- and di(C1-6alkyl)amino-C1-6alkyl, carboxyl-C1-6alkyl, C1-6alkyloxycarbonyl C1-6alkyl, aminocarbonylC1-6alkyl, (C1-4alkyloxy)2-P(=O)-C1-6alkyl, aminosulphonylC1-6alkyl; R6a is hydrogen or C1-6alkyl; R6b is hydrogen, C1-6alkyl, Ar1 or Ar1C1-6alkyl; R6c is C1-6alkyl; Alk is C1-6alkanediyl; R9, R10, R11 are each independently selected from halogen, cyano, C1-6alkyl, Het-C1-6alkyl, Ar1C1-6alkyl, cyano C1-6alkyl, C2-6alkenyl, R6b-O-C3-6alkenyl, C2-6alkynyl, Ar1, R6b-O-, R6b-S-, R6b-O- C1-6alkyl-SO2-, polyhalo-C1-6alkyl, polyhaloC1-6alkyloxy, polyhaloC1-6alkylthio, R6c-C(=O)-, R6b-O-C(=O)-, N(R6aR6b)-C(=O)-, R6b-O-C1-6alkyl, R6b-O-C(=O)-C1-6alkyl, N(R6aR6b)-C(=O)-C1-6alkyl, R6c-C(=O)-NR6b-, N(R6aR6b)-S(=O)2-, H2N-C(=NH)-, and R10 and/or R11 can also be hydrogen; Ar1 is phenyl; Ar2 is phenyl; Het is a heteroring selected from imidazolyl or morpholinyl. The invention also relates to a pharmaceutical composition based on formula (I-b-1) compound, use of formula (I-b-1) compound to prepare a medicinal agent and a method of producing formula (I-b-1) compound.

EFFECT: novel aminobenzimidazole and benzimidazole derivatives with antiviral activity are obtained.

15 cl, 8 tbl, 31 ex

Novel insecticides // 2379301

FIELD: chemistry.

SUBSTANCE: compounds with formula I are described, where each of E and Z is oxygen; A is C1-C6alkylene or a 3-member monocyclic ring system, which can be monosubstituted; Y is C1-C6alkylene; p equals 0; q equals 0 or 1; B represents a 3- or 4-member ring system which is completely or partially saturated and can contain a heteroatom selected from oxygen, possibly substituted; each R1 independently represents halogen, nitro group, C1-C6alkyl; or each R1 independently represents an amino group; n equals 1, 2; each of R2 and R3 represents hydrogen; D represents a group and agronomically acceptable salts of said compounds. Also described is a method of producing formula I compounds, intermediate compounds, a pesticide composition containing a formula I compound, as well as an insect control method and a method of protecting plant propagation material.

EFFECT: novel anthranylamide derivatives have good insecticidal activity.

16 cl, 8 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: proposed phosphodiesterase 4 inhibitors are characterised by formulae II, III, V, VI, where X is CH or N; L is a single bond, -(CH2)nCONH-, -(CH2)nCON(CH2CH3)-, (CH2)nSO2, (CH2)nCO2 or alkylene, optionally substituted oxo or hydroxy; n assumes values from 0 to 3; R1 is optionally substituted alkyl; R3 - H, alkyl, cycloalkyl, alkoxyalkyl, optionally substituted phenyl, phenylalkyl, heterocyclyl, heterocyclylalkyl or cycloalkylalkyl; R4 and R5 represent alkyl; R6 - cycloalkyl, R7 is H; R8 is H, carboxy, alkoxycarbonyl, -CO-alkyl, optionally substituted alkyl.

EFFECT: new phosphodiesterase 4 inhibitors have improved properties.

55 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel quinoline derivatives of formula I or pharmaceutically acceptable salts thereof or esters with tyrosine kinase inhibitor properties. In formula I , R1 is selected from hydroxy, C1-C4-alkoxy, hydroxy(C2-C4-alkoxy), C1-C3-alkoxy-(C2-C4-alkoxy) or from a group of formula Q2-X3 - in which X3 is O, and Q2 is azetidin-1-yl-C2-C4-alkyl, pyrrolidin-1-yl- C2-C4-alkyl, piperidino-C2-C4-alkyl, piperazino-C2-C4-alkyl or morpholino-C2-C4-alkyl; b is 1, 2, or 3; each R2, which can be identical or different, is selected from fluorine, chlorine, bromine, C1-C4-alkyl, C2-C4-alkenyl and C2-C4-alkenyl; Q1 is piperidinyl; a is 0; X1 is CO; X2 is a group of formula: -(CR12R13)P-(Q5)m-, where m is 0 or 1, p is 0, 1, 2, 3 or 4; each of R12 and R13, which can be identical or different, is selected from hydrogen, C1-C6-alkyl, amino, C1-C6-alkylamino and di-[C1-C6-alkyl]amino, and Q5 is C3-C7cycloalkylene; Z is selected from hydroxy, amino, C1-C6-alkylamino, di-[C1-C6-alkyl]amino, C1-C6-alkoxy and a group of formula: Q6-X9-, in which X9 is a single bond and Q6 is heterocyclyl or heterocyclyl-C1-C4 alkyl; under the condition that, if m and p are equal to 0, Z is heterocyclyl.

EFFECT: proposed derivatives can be used in treating proliferative diseases, particularly for treating malignant growths.

32 cl, 4 dwg, 2 tbl, 37 ex

FIELD: medicine.

SUBSTANCE: invention is related to compound represented by formula (1) , in formula A represents nitrogen-containing saturated ring; m represents integer number, equal to 0, 1 or 2; n represents integer number, equal to 1, 2, 3 or 4; G1 represents atom of hydrogen, hydroxyl group or alkoxygroup; G2 represents atom of halogen, hydroxyl group, cyanogroup, alkyl group, alkenyl group, alkinyl group, which may be substituted with hydroxyalkyl group, alkoxygroup, alkyl thiogroup, aminogroup or aryl group; G3 represents atom of hydrogen; G4 represents hydroxyl group or -N(R1)(R2) (R1 and R2 may be identical or different, and independently represent atom of hydrogen, alkyl group, aralkyl group, alkenyl group or saturated heterocyclic group); and G5 represents substituent at carbonic atom, which constitutes nitrogen-containing saturated ring, represented with A, and represents atom of hydrogen, to medicinal agent on the basis of this compound for treatment and prophylaxis of glaucoma, to inhibitor of phosphorylation of regulatory light chain of myosin and inhibitor of kinase Rho/Rho path, and also to method of therapeutical and/or prophylactic treatment of glaucoma.

EFFECT: new compounds have been produced and described, which efficiently inhibit phosphorylation of regulatory light chain of myosin.

32 cl, 42 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention is related to compounds with common formulae I , III , IV and V , value of radicals such as given in formula of invention. Also suggested invention is related to pharmaceutical composition in the basis of above-mentioned compounds, to their use, and also to method of frequent urination treatment, enuresis and increased activity of urinary bladder.

EFFECT: increased efficiency of diseases treatment, in particular for treatment of frequent urination and enuresis, increased activity of urinary bladder and pain.

16 cl, 406 ex, 73 tbl

V:

Amide derivatives // 2375352

FIELD: medicine.

SUBSTANCE: invention refers to new compounds of formula I, to its pharmaceutically acceptable salts exhibiting properties of inhibitors of cytokine production, such as TNF (tumour necrosis factor) and various members of interleukins (IL) family, and properties of kinase inhibitors, particularly p38α kinase. The invention also concerns methods for producing; pharmaceutical compositions and application thereof for making the medicines for treating diseases affected by the compound of the invention with specified activity. In formula I , m represents 0, 1 or 2; R1 represents halogeno, hydroxy, (1-6C) alkyl, (1-6C)alkoxy, (2-6C)alkenyl, (2-6C) alkinyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, amino-(2-6C) alkoxy, (1-6C)alkylamino-(2-6C)alkoxy, di-[(1-6C)alkyl]amino-(2-6C)alkoxy, N-(1-6C)alkylcarbamoyl - (1-6C)alkoxy, di[(1-6C) alkyl]amino-(1-6C)alkyl, hydroxy-(2-6C)alkylamino, heteroaryl-(1-6C)alkoxy, heterocyclyl, heterocyclyloxy and heterocyclyl-(1-6C)alkoxy and wherein any heteroaryl or heterocyclyl group in substitute representing R1, can probably have 1 or 2 substitutes chosen from hydroxy, halogeno, (1-6C) alkyl, (2-6C)alkinyl, (3-6C)cycloalkyl, (3-6C)cycloalkyl-(1-6C)alkyl, (1-6C)alkoxycarbonyl, (2-6C) alkanoyl, halogen-(1-6C)alkyl, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, cyano-(1-6C)alkyl, carboxy- (1-6C)alkyl and methylsulphonyl and wherein any said substitute representing R1 which contains group CH2 attached to 2 carbon atoms, or group CH3 attached to carbon or nitrogen atom, can probably have with each specified group CH2 or CH3, one or two substitutes chosen from halogeno, hydroxy, amino, triflouromethyl, oxo, carboxy, acetamido, (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, (1-6C)alkyamino, di-[(1-6C)alkyl]amino, hydroxy-(1-6C)alkyl, (1-6C)alkoxy-(1-6C)alkyl, halogen-(1-6C)alkyl, (1-6C)alkoxycarbonyl, carbamoyl, N, N-di-[(1-6)alkyl]carbamoyl, (1-6C)alkylsulphonyl, heteroaryl, heteroaryl-(1-6)alkyl and heterocyclyloxy and wherein any heterocyclyl group in substitute representing R1, can probably have 1 oxo-subsitute; R2 represents trifluoromethyl or (1-6C)alkyl; R3 represents hydrogen or (1-6C)alkyl; and R4 represents (3-6C)cycloalkyl, and R4 can be optionally substituted with one or more substitutes chosen from (1-6C)alkyl; and wherein heteroaryl represents aromatic 5- or 6-merous monocyclic ring containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur; heterocyclyl represents saturated 3-10-merous monocyclic or bicyclic ring, each containing one or two heteroatoms chosen from oxygen, nitrogen and sulphur.

EFFECT: improved efficiency.

24 cl, 16 tbl, 66 ex

FIELD: medicine.

SUBSTANCE: invention relates to derivatives of 5- or 6-substituted benzimidazoles, being inhibitory active as regards replication of respiratory syncytial viruses and having formula (I), wherein Q is R6a, piperidinyl, substituted with R6; G is methylene; R1 is piridyl, substituted with 2 substitutes, chosen from hydroxy, C1-6alkyl; one of R2a and R2b is cyano-C2-6alkenyl, Ar3C1-6alkyl, Het-C1-6alkyl, N(R8aR8b)C1-6alkyl, Ar3C2-6alkenyl, Ar3-amino-C1-6alkyl, Het-amino-C1-6alkyl, Het-C1-6alkyl-amino-C1-6alkyl, Ar3tioC1-6alkyl, Ar3amino-carbonyl, Het-amino-carbonyl, Ar3(CH2)ncarbonyl-amino, Het-(CH2)ncarbonyl-amino; and the other of R2a and R2b represents hydrogen; R3 represents hydrogen or C1-6alkyl; in the case when R2a represents hydrogen, R3 represents hydrogen; in the case when R2b represents hydrogen, R3 represents hydrogen or C1-6alkyl; R5 represents hydrogen; R6 represents C1-6alkyl, optionally substituted with one or two substitutes, each of which is independently chosen from group consisting of NR7aR7b, Ar2, hydroxy, amino-carbonyl, amino-sulphonyl; R6a is C1-6alkyl, substituted with one or two substitutes, each of which is independently chosen from group consisting of Ar2, hydroxy or heterocyclic, chosen from a group consisting of piperidinyl, piperazinyl; R7a represents hydrogen; R7b represents hydrogen; R8a represents Ar3, C1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy C1-6alkyl, cyanoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, Ar3C1-6alkyl, HetC1-6alkyl, amino-carbonyl C1-6alkyl, carboxylC1-6alkyl; R8b represents Ar3, C1-6alkyl, hydroxyC1-6alkyl, Ar3C1-6alkyl, HetC1-6alkyl; each independently represents 1; Ar1 represents phenyl; Ar2 represents phenyl or phenyl substituted with one C1-6alkyl-oxy; Ar3 represents phenyl, naphtalenyl, 1,2,3,4-tetra-hydro- naphtalenyl or indanyl, wherein said phenyl, naphtyl, 1,2,3,4- tetra-hydro- naphtalenyl or indanyl can be optionally and each individually substituted with one or more, for example, 2 or 3 substitutes chosen from group consisting of halogen, hydroxy-, mercapto- cyano-, C1-6alkyl, C2-6alkinyl, Ar3 , hydroxy-C1-6alkyl, CF3, cyano-C1-6alkyl, amino-carbonyl, C1-6alkyl-oxy, C1-6alkyltio, Ar1-oxy, Ar1-amino, amino-sulphonyl, amino-carbonylC1-6alkyl, C1-4alkyl-carbonyl, C1-4alkyl-carbonyl-amino and C1-4alko-oxy-carbonyl; Het represents heterocycle chosen from phuranyl, imidazolyl, morpholinyl, piridyl, quinolene, iso-quinolene, each of said heterocycles can be optionally substituted with hydroxyl-Sibalkyl, as well as to acid additional salt thereof and stereo-chemical isomeric forms. In addition, the invention relates to pharmaceutical composition on the basis of compound of formula I and to application of compound of formula I and for production of medicinal preparation.

EFFECT: new derivatives of benzimidazole having useful biological properties.

22 cl, 6 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new a compound of formula I or formula II, or to its pharmaceutically acceptable salts, I II, where X is S; R1 is H or C1-C6alkyl; R2 is NR5R6; R3 is aryl, substituted with a halogen; R4 is H; R5 is H; R6 is H; R7 is CH2NR8R9 where R8 is H, C1-C10alkyl, C3-C8cycloalkyl, aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), heterocycle(C1-C6alkyl), heterocycle(C2-C6alkenyl), hydroxyl(C1-C6alkyl), hydroxyl(C2-C6alkyl), C1-C6alkoxycarbonyl, aryl(C1-C6alkoxy)carbonyl, carbamoyl(C1-C6alkyl); where the above mentioned aryl is an aromatic ring and is not substituted or substituted with one to three substituting groups, each of which, independently from the others, is chosen from: methylenedioxy, hydroxy, C1-C6-alkoxy, halogen, C1-C6alkyl, trifluoromethyl, trifluoromethoxy, NO2, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, NH-acyl, N(C1-C6alkyl)-acyl, hydroxy(C1-C6alkyl), dihydroxy(C1-C6alkyl), CN, C(=O)O(C1-C6alkyl), phenyl, phenyl(C1-C6alkyl), phenyl(C1-C6alkenyl), phenoxy and phenyl(C1-C6alkoxy), R9 is H, C1-C10alkyl, heterocycle(C1-C6alkyl) or heterocycle(C2-C6alkenyl); where the above mentioned heterocycle represents a 5-member saturated monocyclic ring system, consisting of carbon atoms, as well as heteroatoms, chosen from a group comprising N, O, and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes NO2, aryl(C1-C6alkyl), arylsulphonyl; or R8 and R9 together with nitrogen, to which they are bonded, form a heterocycle, which represents a 5 - 7-member saturated monocyclic ring system, consisting of carbon atoms, as well as one to three heteroatoms, chosen from a group comprising N, O and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes C1-C6alkoxy, hydroxy, C1-C6alkyl, C2-C6-alkenyl, C(=O)O(C1-C6alkyl), C(=O)NH2, C(=O)NH(C1-C6alkyl), C(=O)N(C1-C6-alkyl)2, hydroxy(C1-C6alkyl), dihydroxy(C2-C6alkyl), aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), aryl(C1-C6alkoxy) and pyrimidin-2-yl; and m equals 0. The invention also relates to a pharmaceutical composition, as well as to use of formula I or formula II compounds.

EFFECT: obtaining new biologically active compounds, with inhibitory properties towards casein kinase 1ε.

32 cl, 3 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to a quinazoline compound of formula or its pharmaceutically acceptable salts, used as inhibitors of potential-dependant sodium and calcium channels, where R1, R2, R3, R5a, R5, y and x are defined in the formula of invention. The invention also relates to a pharmaceutical composition containing the disclosed compound and to methods of inhibiting one or more of NaV1.2, NaV1.3, NaV1.8, or CaV2.2.

EFFECT: 4-aminoquinazoline antagonists of selective sodium and calcium ion channels.

17 cl, 3 tbl, 1 ex

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