1-benzoylpiperazin derivatives as glycine absorption inhibitors in psychosis treatment

FIELD: chemistry.

SUBSTANCE: invention claims compounds of the formula (I) with radicals as described in the claim, and medicine with inhibition effect on glycine absorption, based on compound of the formula (I) .

EFFECT: medicine for diseases treatment where glycine absorption inhibition can be effective.

21 cl, 1 tbl, 173 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula

g is e Ar denotes a substituted phenyl or substituted 6-membered heteroaryl except 4-pyridine, containing one, two or three nitrogen atom, and phenyl and heteroaryl groups substituted with one or two substituents selected from the group comprising hydroxy, halogen, CN, C1-C6alkyl, C1-C6alkyl substituted by halogen, C1-C6alkoxy, C1-C6alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
R1means hydrogen or C1-C6alkyl;
R2means halogen, C1-C6alkyl, C1-C6alkenyl, where the hydrogen atom is replaced by the group CN, C(O)-R9or C1-C6alkyl, or R2means C2-C6quinil, C1-C6alkyl, substituted with halogen, a saturated or partially saturated -(CH2)n-(C3-C7)cycloalkyl, tetrahydropyranyl, dihydropyran, -C(O)-R9, -(CH2)n-phenyl, or -(CH2)n-5 - or 6-membered heteroaryl containing one or two heteroatoms selected from the group comprising oxygen, sulfur or nitrogen, and phenyl, cycloalkyl and heteroaryl unsubstituted or substituted one, two or three substituents selected from the group comprising hydroxy, halogen, C1-C6alkyl,
C1-C6alkyl substituted by halogen or C1-C6alkoxy;
R3, R4and R6independently from each other mean odor is d, halogen;
R5means NO2, CN, C(O)R9, SO2R10or NR11R12;
R7and R8independently of one another denote hydrogen or C1-C6alkyl;
R9means C1-C6alkyl, C1-C6alkoxy;
R10means C1-C6alkyl, C3-C6cycloalkyl or NR7R8provided that one of the
R7or R8means C1-C6alkyl;
R11and R12together with the nitrogen atom to which they are attached, form a 5-membered heteroaryl group, containing three additional nitrogen atom,
n is 0,
and their pharmaceutically acceptable acid salt additive, provided that these compounds do not mean
1-(2-chloro-5-nitrobenzoyl)-4-(4-methoxyphenyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(4-chlorophenyl)piperazine,
1-(2-fluoro-5-nitrobenzoyl)-4-[2-fluoro-4-(1-oxobutyl)phenyl]piperazine,
1-(2-fluoro-5-nitrobenzoyl)-4-[2-fluoro-4-(1-oxopropyl)phenyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2,3-dimetilfenil)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(3-chlorophenyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-ethoxyphenyl)piperazine,
1-(4-acetyl-2-forfinal)-4-(2-fluoro-5-nitrobenzoyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(4-forfinal)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-methoxyphenyl)piperazine and
1-(4-acetyl-2-fluoro-5-were)-4-(2-fluoro-5-NITR the benzoyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-pyridinyl)piperazine,
1-(4-acetyl-2-forfinal)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperidinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-piperidinyl)benzoyl]piperazine,
1-(4-methoxyphenyl)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-(4-methoxyphenyl)-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-[3-trifluoromethyl]phenyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-pyrimidinyl)piperazine or
1-(2-chloro-5-nitrobenzoyl)-4-(2-forfinal)piperazine.

2. The compounds of formula

where Ar denotes a substituted phenyl or substituted 6-membered heteroaryl except 4-pyridine, containing one, two or three nitrogen atom, and phenyl and heteroaryl groups substituted with one or two substituents selected from the group comprising hydroxy, halogen, CN, C1-C6alkyl, C1-C6alkyl substituted by halogen, C1-C6alkoxy, C1-C6alkoxy substituted by halogen, NR7R8C(O)R9or SO2R0 ;
R1means hydrogen or C1-C6alkyl;
R2means halogen, C2-C6alkenyl,2-C6quinil, C1-C6alkyl substituted by halogen, C3-C7cycloalkyl, saturated or partially saturated tetrahydropyranyl, dihydropyran, -C(O)-R9, phenyl or 5-or 6-membered heteroaryl containing one or two heteroatoms selected from the group comprising oxygen, sulfur or nitrogen, and phenyl, cycloalkyl and heteroaryl unsubstituted or substituted one, two or three substituents selected from the group comprising hydroxy, halogen, C1-C6alkyl, C1-C6alkyl substituted by halogen or C1-C6alkoxy;
R3, R4and R6independently of one another denote hydrogen, halogen;
R5means NO2, CN, C(O)R9, SO2R10or NR11R12;
R7and R8independently of one another denote hydrogen or C1-C6alkyl;
R9means C1-C6alkyl, C1-C6alkoxy;
R10means C1-C6alkyl, C3-C6cycloalkyl or NR7R8provided that one of R7or R8means C1-C6alkyl;
R11and R12together with the nitrogen atom to which they are attached, form a 5-membered heteroaryl group, content is outlined three additional nitrogen atom,
and their pharmaceutically acceptable acid salt additive, provided that these compounds do not mean
1-(2-chloro-5-nitrobenzoyl)-4-(4-methoxyphenyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(4-chlorophenyl)piperazine,
1-(2-fluoro-5-nitrobenzoyl)-4-[2-fluoro-4-(1-oxobutyl)phenyl]piperazine,
1-(2-fluoro-5-nitrobenzoyl)-4-[2-fluoro-4-(1-oxopropyl)phenyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2,3-dimetilfenil)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(3-chlorophenyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-ethoxyphenyl)piperazine,
1-(4-acetyl-2-forfinal)-4-(2-fluoro-5-nitrobenzoyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(4-forfinal)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-methoxyphenyl)piperazine and
1-(4-acetyl-2-fluoro-5-were)-4-(2-fluoro-5-nitrobenzoyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-pyridinyl)piperazine,
1-(4-acetyl-2-forfinal)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperidinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-piperidinyl)benzoyl]piperazine,
1-(4-methoxyphenyl)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-(4-methoxyphenyl)-4-[5-neither the ro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-[3-trifluoromethyl]phenyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-pyrimidinyl)piperazine or
1-(2-chloro-5-nitrobenzoyl)-4-(2-forfinal)piperazine.

3. The compounds of formula I-1 according to claim 1

where R is hydroxy, halogen, CN, C1-C6alkyl, C1-C6alkyl substituted by halogen, C1-C6alkoxy, C1-C6alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
p is 1, 2;
R1means hydrogen;
R2means halogen, C1-C6alkyl, C2-C6alkenyl, where the hydrogen atom is replaced by the group CN, C(O)-R9or C1-C6alkyl, or R2means C2-C6quinil, C1-C6alkyl substituted by halogen, -(CH2)n-(C3-C7)cycloalkyl, saturated or partially saturated tetrahydropyranyl, dihydropyran, -C(O)-R9, phenyl or 5 - or 6-membered heteroaryl containing one or two heteroatoms selected from the group comprising oxygen, sulfur or nitrogen, and phenyl, cycloalkyl and heteroaryl unsubstituted or substituted one, two or three substituents selected from the group comprising halogen, C1-C6alkyl substituted by halogen or C1-C6alkoxy;
R3, R4and R6mean hydrogen;
R5means NO2 or SO2R10;
R7and R8independently of one another denote C1-C6alkyl;
R9means C1-C6alkyl, C1-C6alkoxy;
R10means C1-C6alkyl, C3-C6cycloalkyl or NR7R8provided that one of R7or R8means C1-C6alkyl;
n is 0,
and their pharmaceutically acceptable acid additive salt,
provided that these compounds do not mean
1-(2-chloro-5-nitrobenzoyl)-4-(4-methoxyphenyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(4-chlorophenyl)piperazine,
1-(2-fluoro-5-nitrobenzoyl)-4-[2-fluoro-4-(1-oxobutyl)phenyl]piperazine,
1-(2-fluoro-5-nitrobenzoyl)-4-[2-fluoro-4-(1-oxopropyl)phenyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2,3-dimetilfenil)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(3-chlorophenyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-ethoxyphenyl)piperazine,
1-(4-acetyl-2-forfinal)-4-(2-fluoro-5-nitrobenzoyl)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(4-forfinal)piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-(2-methoxyphenyl)piperazine and
1-(4-acetyl-2-fluoro-5-were)-4-(2-fluoro-5-nitrobenzoyl)piperazine,
1-(4-acetyl-2-forfinal)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperidinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-piperidinyl)benzoyl]piperazine,
1-(4-methoxyphenyl)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-(4-methoxyphenyl)-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-(2-chloro-5-nitrobenzoyl)-4-[3-trifluoromethyl]phenyl]piperazine or
1-(2-chloro-5-nitrobenzoyl)-4-(2-forfinal)piperazine.

4. The compounds of formula I-1 according to claim 3 in which R2means phenyl substituted by three substituents selected from the group comprising halogen, C1-C6alkyl, C1-C6alkyl, substituted with halogen, or C1-C6alkoxy, and other substituents have specified in claim 1 values.

5. The compounds of formula I-1 according to claim 4, for example, the following connections:
1-{3-fluoro-4-[4-(4-nitrobiphenyl-2-carbonyl)piperazine-1-yl]phenyl}Etalon,
(4-methysulfonylmethane-2-yl)[4-(4-triptoreline)piperazine-1-yl]metano,
(4'-fluoro-4-methysulfonylmethane-2-yl)[4-(4-triptoreline)piperazine-1-yl]metano,
[4-(2-fluoro-4-triptoreline)piperazine-1-yl](4-methysulfonylmethane-2-yl)methanon,
(4'-fluoro-4-methysulfonylmethane-2-yl)[4-(2-fluoro-4-triptoreline)piperazine-1-yl]metano,
methylamide 2-[4-(4-triptoreline)piperazine-1-carbonyl] - biphenyl-4-sulfonic acid is you,
3-fluoro-4-[4-(4-methanesulfonamide-2-carbonyl)piperazine-1-yl]benzonitrile or
3-fluoro-4-[4-(2'-fluoro-4-methysulfonylmethane-2-carbonyl)piperazine-1-yl]benzonitrile.

6. The compounds of formula I-1 according to claim 3 in which R2means a saturated or partially saturated With a3-C7cycloalkyl.

7. The compounds of formula I-1 according to claim 6, for example, the following connections:
1-{4-[4-(2-cyclopropyl-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon,
1-{4-[4-(2-cyclohex-1-enyl-5-methansulfonate)piperazine-1-yl]-3-forfinal}Etalon,
(2-cyclohexyl-5-methanesulfonyl)[4-(4-ethyl-2-forfinal)piperazine-1-yl]metano,
1-{4-[4-(2-cyclopent-1-enyl-5-methansulfonate)piperazine-1-yl]-3-forfinal}Etalon,
1-{4-[4-(2-cyclohepta-1-enyl-5-methansulfonate)piperazine-1-yl]-3-forfinal}Etalon,
(2-cyclohepta-1-enyl-5-methanesulfonyl)[4-(4-triptoreline)piperazine-1-yl]metano,
(2-cyclohex-1-enyl-5-methanesulfonyl)[4-(4-triptoreline)piperazine-1-yl]metano,
(2-cyclohexyl-5-methanesulfonyl)[4-(4-triptoreline)piperazine-1-yl]metano or
(2-cyclopentyl-5-methanesulfonyl)[4-(4-triptoreline)piperazine-1-yl]metano.

8. The compounds of formula I-1 according to claim 3 in which R2means tetrahydropyranyl, dihydropyran.

9. The compounds of formula I-1 in step 8, for example, the following connections:
[2-(3,6-dihydro-2H-Piran-4-yl)-5-methanesulfonyl enyl][4-(4-triptoreline)piperazine-1-yl]metano,
[5-methanesulfonyl-2-(tetrahydropyran-4-yl)phenyl][4-(4-triptoreline)piperazine-1-yl]metano,
1-(4-{4-[2-(3,6-dihydro-2H-Piran-4-yl)-5-methansulfonate]piperazine-1-yl}-3-forfinal)alanon or
4-{4-[2-(3,6-dihydro-2H-Piran-4-yl)-5-methansulfonate]piperazine-1-yl}-3-perbenzoate.

10. The compounds of formula I-1 according to claim 3 in which R2means 5 - or 6-membered heteroaryl group containing one or two heteroatoms selected from the group comprising oxygen, sulfur or nitrogen, unsubstituted or substituted C1-C6alkyl.

11. The compounds of formula I-1 in paragraph 10, for example, the following connections:
(5-methanesulfonyl-2-thiophene-2-ylphenyl)[4-(4-triptoreline)piperazine-1-yl]metano,
(5-methanesulfonyl-2-thiophene-3-ylphenyl)[4-(4-triptoreline)piperazine-1-yl]metano,
[5-methanesulfonyl-2-(5-methylthiophene-2-yl)phenyl][4-(4-triptoreline)piperazine-1-yl]metano,
(5-methanesulfonyl-2-pyridine-4-ylphenyl)[4-(4-triptoreline)piperazine-1-yl]metano,
[4-(2-fluoro-4-triptoreline)piperazine-1-yl](5-methanesulfonyl-2-thiophene-3-ylphenyl)methanon or
1-{4-[4-(5-methanesulfonyl-2-thiophene-3-aventyl)piperazine-1-yl]phenyl}Etalon.

12. The compounds of formula I-1 according to claim 3 in which R2means halogen, C1-C6alkyl, C2-C6alkenyl, and the hydrogen atom is replaced by the group CN, C(O)-R9or C1-C6alkyl, or R2 means C2-C6quinil, C1-C6alkyl, substituted with halogen, or-C(O)-R9.

13. The compounds of formula I-1 to 12, for example, methyl ester 2-[4-(4-acetyl-2-forfinal)piperazine-1-carbonyl]-4-nitrobenzoic acid.

14. The compounds of formula I-2 according to claim 1

where R is halogen, C1-C6alkyl substituted by halogen, C1-C6alkoxy, NR7R8about equal to 1, 2;
R1means hydrogen;
R2means phenyl or 5-membered heteroaryl containing as the heteroatom sulfur, and phenyl is unsubstituted or substituted by one Deputy, selected from the group comprising halogen, C1-C6alkoxy;
R3, R4and R6mean hydrogen;
R5means SO2R10;
R7and R8independently of one another denote C1-C6alkyl;
R10means C1-C6alkyl,
and their pharmaceutically acceptable acid salt additive, provided that the excluded heteroaryl group is 4-pyridine.

15. The compounds of formula I-2 through 14, in which R2means phenyl, unsubstituted or substituted by one Deputy, selected from the group comprising halogen, C1-C6alkoxy, and other substituents have specified in claim 1 values.

16. The compounds of formula I-2 to 15, for example, with ewusie connection:
[4-(3-chloro-5-triptorelin-2-yl)piperazine-1-yl](2'-fluoro-4-methysulfonylmethane-2-yl)methanon or
[4-(3-chloro-5-triptorelin-2-yl)piperazine-1-yl](4-methysulfonylmethane-2-yl)methanon.

17. The compounds of formula I-2 through 14, in which R2means a 5-membered heteroaryl group containing, as heteroatom sulfur.

18. The compounds of formula I-2 through 17, for example, [4-(3-chloro-5-triptorelin-2-yl)piperazine-1-yl](5-methanesulfonyl-2-thiophene-3-ylphenyl)methanon.

19. Drug, possess inhibitory activity against absorption of glycine containing compound according to claim 1 and pharmaceutically acceptable excipients.

20. Drug in claim 19, intended for the treatment of diseases which can be useful in the inhibition of the absorption of glycine.

21. Drug for item 21, where the disease includes psychoses, pain, dysfunction in memory and learning, schizophrenia, dementia and other diseases in which there is a lack of cognitive functions, such as violations in the form of loss or Alzheimer's disease.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: there are disclosed 1-(2-aminobenzol)piperazine derivatives of formula (I) and pharmaceutically acceptable acid-additive salts with radical values specified in patent claim. The compounds are characterised with inhibiting effect on glycine I carrier. There is also disclosed medical product based on the compounds of formula (I).

EFFECT: compound can be used for treatment of the diseases associated with glycine uptake inhibition.

12 cl, 5 tbl, 396 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I): wherein R1 represents azido, -OR4, -NHR4 wherein R4 represents hydrogen atom or unsubstituted groups chosen from acyl, thioacyl, (C1-C6)-alkoxycarbonyl, (C3-C6)-cycloalkoxythiocarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy, -C(C=S)-S-(C1-C6)-alkyl, -(C=S)-NH2, -(C=S)-NH-(C1-C6)-alkyl, -C(=S)-N-((C1-C6)-alkyl)2, -C(=S)-NH-(C2-C6)-alkenyl, -C(C=S)-(C=O)-(C1-C6)-alkoxy, thiomorpholinylthiocarbonyl; R2 and R3 can be similar or different and represent independently hydrogen atom, halogen atom, (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl; heterocyclic moiety represents 5-membered heterocycle wherein Z represents sulfur (S), oxygen (O) atom or -NRb wherein Rb represents hydrogen atom or unsubstituted (C1-C6)-alkyl, (C3-C6)-cycloalkyl, aryl or aryl-(C1-C6)-alkyl; Y1 represents group =O or =S ; Y2 and Y3 represent independently hydrogen atom, and if Y2 and Y3 present in common on adjacent carbon atoms then they form 6-membered aromatic cyclic structure substituted if necessary with (C1-C6)-alkyl, or to its pharmaceutically acceptable salt. Also invention relates to a pharmaceutical composition possessing antibacterial activity and containing as an active compound the compound of the formula (I) taken in the effective dose and a pharmaceutically acceptable carrier, diluting agent, excipient. Also, invention relates to method for synthesis of compound of the formula (I). Method for synthesis of compound of the formula (I) wherein R1 represents group -NHR4 wherein R4 means acyl, (C1-C6)-alkoxycarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy and -(C=S)-S-(C1-C6)-alkyl involves acetylation of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 represents hydrogen atom and all symbols are given above and using halide. Method for synthesis of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 means thioacyl, (C3-C6)-cycloalkoxythiocarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl involves the following steps: (i) conversion of compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents hydrogen atom, and all symbols are given above to compound of the formula (I) wherein R1 represents isothiocyanate group by reaction with thiophosgene, and (ii) conversion of compound of the formula (I) wherein R1 represents isothiocyanate group to compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents -C(=S)-OR4d wherein R4d represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C2-C6)-alkenyl, and all symbols are given above, in reaction with alcohol. Compounds of the formula (I) are used in treatment of bacterial infection that involves administration of compound of the formula (I) in a patient needing in this treatment. Invention provides synthesis of oxazolidinone compounds possessing antibacterial activity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

7 cl, 1 tbl, 144 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-phenyltetrahydroisoquinoline of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another hydrogen (H), fluorine (F), chloride (Cl), bromine (Br) atoms, CaH2a+1 wherein one or more atoms H are substituted with F, -NR11R12 or -SOj-R15 wherein a = 1-8; R11 and R12 mean independently of one another H, CeH2e+1 or CrrH2rr-1 wherein e = 1-4; rr = 3, 4, or in common with nitrogen atom to which they are bound form a cycle chosen from group consisting of pyrrolidinyl, piperidinyl, N-methylpiperazinyl, piperazinyl or morpholine; j = 1 or 2; R15 means CkH2k+1 wherein k = 1-8; R5 means CpH2p+1 or CssH2ss-1; p = 1-8; ss = 3-8; R6 means H; R7, R8 and R9 mean independently of one another mean -SOwR23, -NR32COR30, NR32CSR30, -NR32SObbR30, H, F, Cl, Br, -OH, -NH2, CeeH2ee+1, -NR40R41, -CONR40R41 or -COOR42 wherein w = 0, 1 or 2; bb = 2 or 3; R23 means NR25R26 wherein R25 and R26 mean independently of one another H or CzH2z+1, CzzH2zz-1 wherein z = 1-8; zz = 3-8 wherein in CzH2z+1 and CzzH2zz-1 one or more H atoms are substituted with fluorine atom and one or more CH2-groups are substituted with -C(=O) or NR27 wherein R27 means H or CaaH2aa+1 wherein aa = 1-4; or R25 and R26 in common with nitrogen atom to which they are bound form 5-, 6- or 7-membered cycle; R30 means H, CccH2cc+1, CyyH2yy-1, pyrrolydinyl, piperidinyl wherein in their cycles CH2-group can be substituted with oxygen atom (O) or -NR33; R32 and R33 mean independently of one another H or ChH2h+1 wherein cc = 1-8; yy = 3-8; h = 1-8 wherein in the group ChH2h+1 one or more hydrogen atoms are substituted with fluorine atom, and in the groups CccH2cc+1 and CyyH2yy-1 one or more hydrogen atoms can be substituted with fluorine atom, and CH2-group can be substituted with O or -NR31 wherein NR31 means H, methyl, ethyl, acetyl or -SO2CH3; or R30 means 6-membered heteroaryl with 1-4 nitrogen atoms, 0 or 1, S-atoms or 0, or 1 O-atom that represents unsubstituted or substituted with up to three substitutes chosen from group consisting of F, Cl, Br, J, CooH2oo+1 wherein one or more hydrogen atoms can be substituted with fluorine atom, -NO2 or -NR70R71 wherein oo = 1-8; R70 and R71 mean independently of one another H, CuuH2uu+1 or -COR72 wherein uu = 1-8; R72 means H, CvvH2vv+1 wherein vv = 1-8; ee = 1-8; R40 and R41 mean independently of one another H, CttH2tt+1 or -C(NH)NH2 wherein tt = 1-8 and wherein in the group CttH2tt+1 one or more CH2-groups can be substituted with NR44 wherein R44 means CggH2gg+1 wherein gg = 1-8; R42 means H or ChhH2hh+1 wherein hh = 1-8 being, however, two substitutes from group R7, R8 and R9 can't mean -OH simultaneously, and at least one residue from R7, R8 and R9 must be chosen from group consisting of -CONR40R41, -OvSOwR23, -NR32COR30, -NR32CSR30 and -NR32SObbR30. Also, invention relates to using above given compounds for preparing a medicinal agent. Also, invention considers a medicinal agent representing inhibitor of sodium-proton exchange of subtype III (NHE3) based on proposed compounds. Invention provides synthesis of novel compounds, a medicinal agent based on thereof for aims of treatment of such diseases as nervous system ischemia, insult and brain edema, in treatment of snore, shock, impaired respiratory impulse, as purgative agents, as agents against extoparasites, for prophylaxis of gall stones formation, as anti-atherosclerotic agents, agents against diabetes mellitus later complications, cancer diseases, fibrous diseases, endothelial dysfunction, hypertrophies and hyperplasia of organs and others.

EFFECT: valuable medicinal properties of compounds and medicinal agents.

21 cl, 15 tbl, 221 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (1): wherein Y means -O-, -S- or -N(R2)- wherein R2 means hydrogen atom, (C1-C10)-alkyl or aralkyl; Z means 2,5-furanyl, 2,5-thiophenyl, 4,4'-stilbenyl or 1,2-ethyleneyl residue; R1 means hydrogen or halogen atom, (C1-C10)-alkyl, (C1-C10)-alkoxy-group, cyano-group, -COOM or -SO3M wherein M means hydrogen atom or alkaline or alkaline-earth metal atom. Method for synthesis involves carrying out the reaction of compound of the formula (2): with dicarboxylic acid of the formula: HOOC-Z-COOH (3) or with it ester wherein Y, Z and R1 have values given above in N-methylpyrrolidone or N,N-dimethylacetamide medium in the presence of an acid catalyst and optionally in the presence of an accessory solvent able to remove water from the reaction mixture.

EFFECT: improved method of synthesis.

11 cl, 7 ex

FIELD: organic chemistry, technology of organic compounds.

SUBSTANCE: invention relates to heterocyclic o-dicarbonitriles. Invention describes heterocyclic o-dicarbonitriles of the general formula: wherein R means the following compounds: . Heterocyclic o-dicarbonitriles can be used for preparing hexazocyclanes-fluorophores as a donor-fragment used for preparing hexazocyclanes-bifluorophores and hexazocyclanes-trifluorophores. Invention provides preparing new compounds possessing valuable properties.

EFFECT: valuable properties of compounds.

2 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

The invention relates to novel polycyclic to dihydrothiazolo General formula (I), where Y is a simple bond; X is CH2; R1 is H, F, Cl, NO2, CN, COOH, (C1-C6)-alkyl, (C2-C6)-quinil, O-(C1-C6)-alkyl, and alkyl residues one, several or all of the hydrogen atoms may be replaced by fluorine; (CH2)n-phenyl, SO2-(C1-C6)-alkyl, and n = 0 and the phenyl residue up to twice may be substituted by F, Cl, CF3, OCF3, O-(C1-C6)-alkyl, (C1-C6)-alkyl; O-(CH2)n-phenyl, and n = 0 and phenyl cycle can be one - to twofold substituted by Cl, (C1-C6)-alkyl; 1 - or 2-naphthyl, 2 - or 3-thienyl; R1' is hydrogen; R2 is H, (C1-C6)-alkyl, R3 is hydrogen; R4 - (C1-C8)-alkyl, (C3-C7-cycloalkyl, (CH2)n-aryl, and n = 0-1, and aryl can be phenyl, 2-, 3 - or 4-pyridyl, 2 - or 3-thienyl, 2 - or 3-furyl, indol-3-yl, indol-5-yl, and aryl or heteroaryl residue up to twice may be substituted by F, Cl, HE, OCF3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, 2-, 3-, 4-pyridium, pyrrol-1-yl, with peregrinae ring may be substituted CF3; and their physio is

FIELD: organic chemistry, biochemistry.

SUBSTANCE: invention relates to compounds of the formula (I): wherein R1 means -lower alkyl, -CH2-aryl, -cycloalkyl, -(CH2)3, -OC(=O)CH3, -lower alcohol, -lower alkyl-R10, -CH2COOH or -CH2CH2OCH2CH3; R2 means -lower alkyl, -CH2-aryl, -lower alcohol, -CH2C(=O)-NH2 or lower alkyl-R10 wherein at least one radical among R1 or R2 means -CH3; R3 means -COOH, -lower alkyl-COOH, -lower alcohol, -CH2OCH2, -CH2NH2, -CHNHSO2R11, -C(=O)-R12, -(CH2)nNHC(=O)-R13, -(CH2)mC(=O)N-(R15)(R16), -C(=NH)-R17 or -(CH2)n-R18; R4 means hydrogen atom (-H), -lower alkoxy group, -O-C(R7R8)C(=O)-R19, -halogen atom, -SCH3, -C=CHC(=O)-R10, -CH2CH2C(=O)-R10, -O-lower alcohol, -OCH2CH(OH)CH2N=N±N-, -OCH2CH2OCH2CH2Cl, -NHC9=O)-CH2-lower alkyl, -O(CH2)n-cycloalkyl, -O-lower alkene or 5-membered unsaturated heterocyclic ring comprising one heteroatom representing sulfur (S) or oxygen (O) atom; R5 and R6 mean independently -H, -halogen atom or -lower alkoxy group; R7 and R8 mean independently -H or -CH3; R10 means 5-6-membered saturated heterocyclyl comprising 1 or 2 heteroatoms, such as N and O, and this group is bound with other moiety of molecule by a ring N atom; R11 means -CF3, -lower alkyl, -CH2Cl, -CH2CF3 or -R12; R12 means 5-6-membered saturated substituted or unsubstituted heterocyclic ring comprising 1 heteroatom, such as N, O and S wherein substituted ring represents heterocyclic ring substituted with -OH or -phenyl; R13 means -lower alkyl, -lower alkoxy group or -(CH2)nR14; R14 means 5-6-membered saturated or unsaturated heterocyclic ring comprising 1 and 2 heteroatoms, that are chosen from group comprising N and O; R15 means -H, -lower alkyl, -OH, -lower alkoxy group or -CH2COOCH2CH3; R17 means -lower alkoxy group, -NH2 or -N-lower alkyl; R18 means saturated or unsaturated 5-membered substituted or unsubstituted heterocyclic ring comprising from 1 to 4 heteroatoms, such as N, O and S wherein substituted ring represents heterocyclic ring that is substituted by one or two cyclic carbon atoms by =O, or it is substituted by cyclic N atom by -lower alcohol or -lower alkyl; R19 means -OH, -NHCH(CH3)2, -N(CH3)CH2-aryl, -N(CH3)-lower alkyl, 1-(aryl-(CH2)n-)-[1,4]-diazin-4-yl or 5-6-membered saturated heterocyclyl and optionally substituted with lower alkyl comprising 1 or 2 heteroatoms, such as N and O; m = 0, 1 or 2; n = 0 or 1, and their pharmaceutically acceptable salts and esters. Also, invention relates to a pharmaceutical composition possessing inhibitory activity with respect to GFAT and containing the effective amount of compound of the formula (I). Invention provides expanding assortment of agents possessing inhibitory activity with respect to GFAT. Proposed compounds can be used as inhibitors of GFAT, and pharmaceutical composition possessing inhibitory activity with respect to GFAT containing above said compound of the formula (I) also.

EFFECT: valuable biochemical properties of compounds and pharmaceutical composition.

25 cl, 134 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new 1-(p-thienylbenzyl)-imidazoles of the formula (I): , wherein indicated residues represent the following values: R(1) means halogen atom, (C1-C4)-alkoxyl, (C1-C8)-alkoxyl wherein one carbon atom can be replaced with heteroatom oxygen atom (O); R(2) means CHO; R(3) means aryl; R(4) means hydrogen halogen atom; X means oxygen atom; Y means oxygen atom or -NH-; R(5) means (C1-C6)-alkyl; R(6) means (C1-C5)-alkyl in their any stereoisomeric forms and their mixtures taken in any ratios, and their physiologically acceptable salts. Compounds are strong agonists of angiotensin-(1-7) receptors and therefore they can be used as a drug for treatment and prophylaxis of arterial hypertension, heart hypertrophy, cardiac insufficiency, coronary diseases such as stenocardia, heart infarction, vascular restenosis after angioplasty, cardiomyopathy, endothelial dysfunction or endothelial injures, for example, as result of atherosclerosis processes, or in diabetes mellitus, and arterial and venous thrombosis also. Invention describes a pharmaceutical composition based on above said compounds and a method for their applying also.

EFFECT: valuable medicinal properties of compounds and composition.

10 cl, 19 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of benzimidazole represented by the following formula (I) or its salt:

wherein R1 represents (lower)-alkyl group; R2 represents aromatic (lower)-alkyl group that can be substituted with one or more groups taken among halogen atom, alkyl group, halogen-(lower)-alkyl group, nitro-group, aromatic group, aromatic (lower)-alkoxy-group, (lower)-cycloalkyloxy-(lower)-alkyl group, aromatic (lower)-alkyl group, aromatic (lower)-alkenyl group, aromatic (lower)-alkynyl group, aromatic oxy-(lower)-alkyl group, (lower)-cycloalkyl-(lower)-alkoxy-group, alkenyl group, (lower)-alkoxy-group, (lower)-alkylthio-group and (lower)-alkanesulfonylcarbamoyl group; R3 represents alkyl group, hydroxy-(lower)-alkyl group, alkenyl group, aromatic group, halogenated aromatic group, (lower)-alkyl aromatic group, (lower)-alkenyl aromatic group or aromatic (lower)-alkenyl group; -X- represents cross-linking group represented by one of the following formulas: (II) , (III) , (IV) , (V) . Also, invention relates to pharmaceutical compositions eliciting activity that reduces blood glucose level based on this compound. Invention provides preparing new compounds and pharmaceutical compositions based on thereof used for prophylaxis and treatment of damaged tolerance to glucose, diabetes mellitus, insulin-resistance syndrome, vascular failures syndrome, hyperlipidemia and cardiovascular disorders.

EFFECT: valuable medicinal properties of compounds and compositions.

16 cl, 1 tbl, 86 ex

The invention relates to new imidazole derivative of the formula (I):where R1represents phenyl or pyridinyl, substituted by substituents selected from the group comprising (1) phenyl, (2) furyl, thienyl, (3) halogen, (4) halogen(lower)alkyl, (5) lower alkylthio, (6) nitro, (7) lower alkenyl, optionally substituted phenyl, (8) lower quinil, optionally substituted phenyl, (9) lower alkoxy, optionally substituted cyclo(lower)alkyl or phenyl, (10) lower alkyl, optionally substituted, phenyloxy or (11) amino, optionally substituted protected carboxyla; R2represents lower alkyl; R3represents halogen or lower alkyl; R4represents (1) lower alkenyl, optionally substituted phenyl, (2) phenyl, optionally substituted lower alkyl or lower alkenyl, (3) lower alkyl or (4) thienyl, optionally substituted with halogen; a represents a lower alkylene and L represents a simple bond, a lower albaniles or lower alkylene, optionally substituted phenyl or pyridinyl, or-X-CH2- where X represents O or NR5where R5represents hydrogen or n is

The invention relates to the field of organic chemistry, specifically to new connections: dicyanodiamide, namely aralen-bis(2-aminothiophene-3-carbonitrile)am General formula

where R represents

Connection most effectively can be used as monomers for obtaining polyamides, polyazomethines and politician with phenylanaline groups with high values of viscosity and conductivity

The invention relates to new substituted phenyl derivatives, which are strong blockers chlorine ion channels and as such are useful in the treatment of sickle cell anemia, cerebral edema that accompanies ischemia or tumor, diarrhea, hypertension (diuretic), osteoporosis and to reduce the intraocular pressure for the treatment of disorders such as glaucoma

The invention relates to piperazine derivatives of General formula I, in which R1denotes pyridyl or phenyl, unsubstituted or once substituted Ph or 2 - or 3-Tiepolo, R2indicates Ph1or Het

The invention relates to benzimidazole derivative of the formula (I)

or its pharmaceutically acceptable salt, where Rrepresents a group of formula -(ALK)q-R1where (ALK) represents alkyl, alkenyl or quinil, q is 0 or 1, R1represents a group of formula-CO2R2where R2is hydroxyalkyl, alkoxyalkyl or toolboxitem, Rrepresents a group of the formula

where o is 0 or 1, n is 0, 1 or 2, X represents N or CH, Y is O, NR11or CHR11where R11represents hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, carboxyl, or acyl, or a group of the formula -(alkyl)p-CN, -(alkyl)p-aryl, -(alkyl)p-O-aryl, -(alkyl)p-O-aralkyl, -(alkyl)p"heterocycle", -(alkyl)p-CO2"heterocycle" or -(alkyl-CO2)s-(alkyl)t-COR5and , in these formulas, R, s and t independently of each other 0 or 1, "heterocycle" represents a 5 the n heteroatom, represents a nitrogen, oxygen or sulfur, and which may substituted once or more than once, by substituents selected from the group consisting of halogen, alkyl and oxo, R5represents a hydroxy, alkoxy, hydroxy-C1-8-alkoxy, C1-8-alkoxyalkane, Tiltonsville, aryl, or aralkyl, or a group of the formula-NR6R7or-O-alkyl-NR6R7and , in these formulas, R6and R7independently of one another represent hydrogen or alkyl, and R14and R15independently of one another represent hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, carboxyl or acyl; or where R' is a group of formula -(ALK)q-R1where (ALK) represents alkyl, alkenyl or quinil, q is 0 or 1, R1represents fornillo group; and Rrepresents -(alkyl)m-CO2R8where m is 0 or 1, R8represents a group of formula -(alkyl)p-NR9R10where R is 0 or 1, and R9and R10together with the nitrogen atom to which they are attached, form a piperazinilnom group, possibly substituted by acyl

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