Benzoxazine and quinoxaline derivatives and use thereof

FIELD: chemistry.

SUBSTANCE: described are compounds of formula ; or their pharmaceutically acceptable salts, where A is phenyl, X is CH2- or C=O; Y is O; k equals 1; m equals 0; R2 and R3 each independently represents hydrogen or alkyl, R4 is a group of formula or . Disclosed compounds have selective affinity to 5-HT6 and 5-HT2A receptors. Also described is a pharmaceutical composition containing said compounds and use of the said compounds in making a medicinal agent for treating diseased conditions of the central nervous system.

EFFECT: more effective treatment.

49 cl, 1 tbl, 16 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

or its pharmaceutically acceptable salt, where
Ar represents phenyl,
X represents-CH2or C=O;
Y represents O;
it is equal to 1;
m is 0;
R2and R3each independently represents hydrogen or alkyl;
R4represents a group which has the formula
or;
Z represents a bond, -(C=O)-;
n is from 0 to 4;
p is 0 or 1;
u and v each independently represents 1 or 2;
R5and R6each independently represents hydrogen or alkyl; and
R7and R8each independently represents hydrogen, alkyl, -(C=NRg)-NRhRior -(CH2)2-NRhRiwhere Rg, Rhand Rieach independently represents hydrogen or alkyl, or R7and R8together with the nitrogen atom to which they are attached, may form a four-, five - or six-membered ring which may include an additional heteroatom selected from N, or one of R5and R6together with one of R7and R8together with the atoms to which they are attached, may form a ring of 5 members, which may include additional heteroatom n

2. The compound according to claim 1, where X represents-CH2-.

3. The compound according to claim 2, where R2and R3represent hydrogen.

4. The compound according to claim 2, where Z represents a-C(=O)-.

5. The compound according to claim 4, where n is 0 and p is 0.

6. The compound according to claim 5, where R7represents hydrogen and R8represents -(C=NRd)-NReRf.

7. The compound according to claim 5, where R7represents the t of a hydrogen and R 8represents -(CH2)2-NRgRh.

8. The compound according to claim 4, where n is 0 and p is 1.

9. The connection of claim 8, where R5and R6represent hydrogen.

10. The connection according to claim 9, where R7and R8each independently represents hydrogen or alkyl.

11. The connection of claim 8, where one of R5and R6and one of R7and R8together with the atoms to which they are attached, form a ring of 5 members.

12. The compound according to claim 4, where n is 1 and p is 1.

13. The connection section 12, where R5and R6represent hydrogen.

14. The connection indicated in paragraph 13, where R7and R8each independently represents hydrogen or alkyl.

15. The connection 14, where one of R5and R6and R7and R8together with the atoms to which they are attached, form a ring of 5 members.

16. The connection indicated in paragraph 15, where one of R5and R6and R7and R8together with the atoms to which they are attached, form imidazolidinone ring.

17. The compound according to claim 2, where Z is a bond.

18. The connection 17, where n is 0 and p is 1.

19. Connection p, where one of R5and R6and R7and R8together with the atoms to which they are attached, form a ring of 5 members.

20. The connection 17, where n is 1 and p is 1.

21. Connection claim 20, where R 5and R6represent hydrogen.

22. Connection item 21, where R7and R8each independently represents hydrogen or alkyl.

23. Connection claim 20, where one of R5and R6and R7and R8together with the atoms to which they are attached, form a ring of 5 members.

24. Connection item 23, where one of R5and R6and R7and R8together with the atoms to which they are attached, form imidazolidinone ring.

25. The connection 17, where n is 2 and p is 1.

26. Connection A.25, where R5and R6represent hydrogen.

27. Connection item 21, where R7and R8each independently represents hydrogen or alkyl.

28. The connection 17, where n is 3 and p is 1.

29. Connection p, where R5and R6represent hydrogen.

30. The connection clause 29, where R7and R8each independently represents hydrogen or alkyl.

31. The compound according to claim 1, where R4represents: aminoalkyl; acylaminoalkyl; dialkylaminoalkyl; imidazolylalkyl; imidazolylalkyl; piperidinyl; pyrrolidinyl; azetidine; pyridinyl; piperidinyloxy; pyrrolidinyloxy; azetidine; aminoalkylsilane; alkylaminocarbonyl; dialkylaminoalkyl; imidazolylalkyl; imidazolylalkyl; aminoalkylation bonil; guanidiniocarbonyl; piperidinylcarbonyl; pyrrolidinylcarbonyl; azetidinone; pyridylcarbonyl; piperidinylcarbonyl; pyrrolidinylcarbonyl or azeridemiryolbank.

32. Connection p, where R4represents: aminoalkyl; acylaminoalkyl; dialkylaminoalkyl; imidazolylalkyl; imidazolylalkyl; piperidinyl; pyrrolidinyl; pyridinyl; azetidine; aminoalkylsilane; alkylaminocarbonyl; dialkylaminoalkyl; imidazolylalkyl-carbonyl; aminoethylaminomethyl; guanidiniocarbonyl; piperidinylcarbonyl; pyrrolidinylcarbonyl or azetidinone.

33. Connection p, where R4represents: 2-dimethylaminoethyl; 3-dimethylaminopropyl; 4-dimethylaminomethyl; 2-amino-ethyl; 3-methylaminopropyl; imidazolin-2-ylmethyl; piperidine-4-yl; 2-imidazol-1-yl-ethyl; azetidin-3-ylmethyl; pyrrolidin-3-yl; pyridin-4-yl; imidazolin-2-iletileri; guanidiniocarbonyl; 2-aminoethylaminomethyl; 2-dimethylaminoethanol; 2-methylaminoethanol; methylaminomethyl, dimethylaminomethylphenol; 2-aminoethylaminomethyl; azetidin-3-yl-carbonyl; pyrrolidin-3-yl-carbonyl; piperidine-3-yl-carbonyl or piperidine-4-yl-carbonyl.

34. The compound according to claim 1, where R4represents a
,, ,,,,,
,,,,,,,,,or.

35. The compound according to claim 1, where the specified compound has the formula IIa or IIb
;and
m, R1, R2, R3and R4are as set forth in claim 1.

36. Connection p, where R4represents: aminoalkyl; acylaminoalkyl; dialkylaminoalkyl; imidazolylalkyl; imidazolylalkyl; piperidinyl; pyrrolidinyl, azetidine; pyridinyl; piperidinyloxy; pyrrolidinyloxy; azetidine; aminoalkylsilane; alkylaminocarbonyl; dialkylaminoalkyl, imidazolylalkyl, imidazolylalkyl; aminoethylaminomethyl, guanidiniocarbonyl, piperidinylcarbonyl; pyrrolidinylcarbonyl; azetidinone; pyridylcarbonyl; piperidinylcarbonyl; pyrrolidinylcarbonyl or azeridemiryolbank.

37. Connection p, where R4represents aminoalkyl, alkilani alkyl; dialkylaminoalkyl; imidazolylalkyl; imidazolylalkyl; piperidinyl; pyrrolidinyl; pyridinyl; azetidine; aminoalkylsilane; alkylaminocarbonyl; dialkylaminoalkyl; imidazolylalkyl; aminoethylaminomethyl; guanidiniocarbonyl; piperidinylcarbonyl; pyrrolidinylcarbonyl or azetidinone.

38. The connection clause 37, where R4represents: 2-dimethylaminoethyl; 3-dimethylaminopropyl; 4-dimethylaminomethyl; 2-amino-ethyl; 3-methylaminopropyl; imidazolin-2-ylmethyl; piperidine-4-yl; 2-imidazol-1-yl-ethyl; azetidin-3-ylmethyl; pyrrolidin-3-yl; pyridin-4-yl; imidazolin-2-iletileri; guanidiniocarbonyl; 2-aminoethylaminomethyl; 2-dimethylaminoethanol; 2-methylaminoethanol; methylaminoethanol; dimethylaminomethylene; 2-aminoethylaminomethyl; azetidin-3-yl-carbonyl; pyrrolidin-3-yl-carbonyl; piperidine-3-yl-carbonyl or piperidine-4-yl-carbonyl.

39. Connection p, where R4represents a
,,,,,,,
,,,,, ,,,,or.

40. The compound according to claim 1, where the specified compound has the formula IIIa or IIIb
;;
where n, p, R5, R6, R7and R8are as set forth in claim 1.

41. The compound according to claim 1, where the specified connection has the formula IVa or IVb

where n, p, R5, R6, R7and R8are as set forth in claim 1.

42. The compound according to claim 1, where the specified compound has the formula Va or Vb,
;;
where u and v each independently is 1 or 2.

43. The connection at paragraph 41, where the aforementioned compound has formula VIa or VIb
;;
n, R7, R8are as set out in paragraph 41.

44. The compound according to claim 1, where the specified connection has the formula VIIa or VIIb
;;
where u and v each independently is 1 or 2.

45. The compound according to claim 1, where the specified connection selected from the group consisting of
7-Benzazolyl-4-(2-dimethylamino-ethyl)-4H-benzo[1,4]oxazin-3-one;
7-Benzazolyl-4-(3-dimethylamino-propyl)-4H-benzo[1,4]is casin-3-one;
4-(2-Amino-ethyl)-7-benzazolyl-4H-benzo[1,4]oxazin-3-one;
7-Benzazolyl-4-(4-dimethylamino-butyl)-4H-benzo[1,4]oxazin-3-one;
7-Benzazolyl-4-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4H-benzo[1,4]oxazin-3-one;
6-Benzazolyl-4-(2-dimethylamino-ethyl)-4H-benzo[1,4]oxazin-3-it,
6-Benzazolyl-4-(4,5-dihydro-1H-imidazol-2-ylmethyl)-4H-benzo[1,4]oxazin-3-one;
2-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethylamine;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-(4,5-dihydro-1H-imidazol-2-yl)-ethanone;
6-Benzazolyl-4-(4,5-dihydro-1H-imidazol-2-ylmethyl)-3,4-dihydro-2H-benzo[1,4]oxazine;
N-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-carbonyl)-guanidine;
6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-carboxylic acid (2-amino-ethyl)-amide;
6-Benzazolyl-4-piperidine-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-3-dimethylamino-propane-1-it;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-3-methylamino-propane-1-it;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-methylamino-ethanone;
[3-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propyl]-methyl-amine;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-dimethylamino-ethanone;
7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-carboxylic acid (2-amino-ethyl)-amide;
1-(7-Benzazolyl-,3-dihydro-benzo[1,4]oxazin-4-yl)-2-(4,5-dihydro-1H-imidazol-2-yl)-ethanone;
N-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-carbonyl)-guanidine;
7-Benzazolyl-4-piperidine-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine;
2-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethylamine;
1-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-methylamino-ethanone;
1-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-3-methylamino-propane-1-it;
[3-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propyl]-methyl-amine;
7-Benzazolyl-4-(2-imidazol-1-yl-ethyl)-3,4-dihydro-2H-benzo[1,4]oxazine;
Azetidin-3-yl-(7-benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-methanone;
4 Azetidin-3-ylmethyl-7-benzazolyl-3,4-dihydro-2H-benzo[1,4]oxazine;
(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-pyrrolidin-3-yl-methanone;
(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-piperidine-3-yl-methanone;
(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-piperidine-4-yl-methanone;
7-Benzazolyl-4-pyrrolidin-3-yl-3,4-dihydro-2H-benzo[1,4]oxazine;
7-Benzazolyl-2,2-dimethyl-4-pyridin-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine and
7-Benzazolyl-2,2-dimethyl-4-piperidine-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine.

46. The compound according to claim 1, where the specified connection selected from the group consisting of:
2-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethylamine;
6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-carboxylic KIS is the notes (2-amino-ethyl)-amide;
6-Benzazolyl-4-piperidine-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-3-dimethylamino-propane-1-it;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-3-methylamino-propane-1-it;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-methylamino-ethanone,
[3-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propyl]-methyl-amine;
1-(6-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-dimethylamino-ethanone;
7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-carboxylic acid (2-amino-ethyl)-amide;
7-Benzazolyl-4-piperidine-4-yl-3,4-dihydro-2H-benzo[1,4]oxazine;
2-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-ethylamine;
1-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-methylamino-ethanone;
1-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-3-methylamino-propane-1-it;
[3-(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propyl]-methyl-amine;
7-Benzazolyl-4-(2-imidazol-1-yl-ethyl)-3,4-dihydro-2H-benzo[1,4]oxazine;
Azetidin-3-yl-(7-benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-methanone;
4 Azetidin-3-ylmethyl-7-benzazolyl-3,4-dihydro-2H-benzo[1,4]oxazine;
(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-pyrrolidin-3-yl-methanone;
(7-Benzazolyl-2,3-dihydro-benzo[1,4]oxazin-4-yl)-piperidine-3-yl-methanone;
(7-Benzazolyl-2,3-dihydro-benzo[14]oxazin-4-yl)-piperidine-4-yl-methanone and
7-Benzazolyl-4-pyrrolidin-3-yl-3,4-dihydro-2H-benzo[1,4]oxazine.

47. Pharmaceutical composition having a selective affinity for the receptors 5-MT and 5-NTA containing an effective amount of a compound according to claim 1 in a mixture with a pharmaceutically acceptable carrier.

48. The use of the compounds of formula I according to claim 1 for the manufacture of drugs for the treatment of painful conditions of the Central nervous system of the subject.

49. Use p, where a painful condition selected from psychosis, schizophrenia, manic depressions, neurological disorders, memory disorders, disorders associated with attention deficit, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, eating disorders and Huntington's disease.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to compound of formula I wherein X represents -S- or -NH-; R1 represents C1-12alkyl, C2-12alkenyl, phenyl C1-12alkel, phenyl C2-12alkenyl or phenyl-O-C1-12alkyl and wherein said phenyl groups are optionally substituted with one or two assistants chosen from the group consisting of lower C1-7alkyl, C C1-7alkoxy and halogen C1-7alkyl; R2 represents hydrogen, lower C1-7alkyl or C3-6cycloalkyl; R3/R4 together with N-atom whereto attached, form nonaromatic 5,6-members heterocyclic ring system which optionally contains in addition to N-atom one additional heteroatom chosen from the group, consisting of O or N and where the ring system is optionally substituted group lower C1-7alkyl, lower C1-7alkoxy, -NR2, -CONR2; or R3/R4 together with N-atom whereto attached, can form heterocyclic ring system which contains at least two rings and which optionally contains one or two additional heteroatoms chosen from group, consisting of N and O; R represents hydrogen or lower C1-7alkyl; R5 represents hydrogen or lower C1-7alkyl; or to pharmaceutically acceptable additive salts with acid of this compound. The invention also concerns a medical product.

EFFECT: improved clinical effectiveness.

16 cl, 4 dwg, 3 tbl, 43 ex

FIELD: chemistry.

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EFFECT: improved method.

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FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[1-(methylsulfonyl) piperidin-4-yl]propyl}piperidin-4-yl)-N-ethyl-2-[4- (methylsufonyl)phenyl]acetamide or its pharmaceutically acceptable salts. The invention also relates to a method for synthesis of the compound in paragraph 1, as well as to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with activity towards CCR5 (chemokine receptor 5).

6 cl, 6 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention is related to new compounds of common formula IC1: , where A represents cyano; B represents hydrogen; R1, R2, R3 and R4 independently represent hydrogen; alkyl; halogen or nitro; R5 and R6 independently represent hydrogen; alkyl; cycloalkyl; cycloalkylalkyl; heteroaryl; heteroarylalkyl; alkenyl; carboxyalkyl; cyanoalkyl; diphenylalkyl; aryl, arylalkoxyaryl, arylalkyl, arylalkylaryl, arylcarbonylaryl or aryloxyaryl, or R5 and R6, together with atom of nitrogen, to which they are connected, create heterocyclic ring system; or to salts of such compound; at the same time "heteroaryl" used separately or in combination, is related to mono-, bi- or tricyclic aromatic ring system, which contains up to 14 atoms included in ring, in which at least one ring contains at least one heteroatom, independently chosen from nitrogen, oxygen or sulfur, besides specified heteroaryl group may be unsubstituted or substituted with one to three substituents, independently selected from alkyl and alkoxy; 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{3-[(E)-2-(3-chloro-4-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(3-phenylpropylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2,3-dichlorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-(5-chloro-2-methylphenylcarbamoyl)-2-cyanovinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(4-methoxybenzylcarbamoyl)vinyl]indole-1-yl}acetic acid; {3-[(E)-2-cyano-2-(2-fluorophenylcarbamoyl)vinyl]indole-1-yl}acetic acid; and {3-[(E)-2-cyano-3-oxo-3-(4-phenyl-piperazine-1-yl)propenyl]indole-1-yl}acetic acid. 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EFFECT: production of biologically active compounds, which have activity of antagonist coupled with G-protein of chemoattractant receptor of molecules homologue released by Th2-cells.

11 cl, 156 ex, 8 tbl

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 relates to formula (I) compounds and to their use in treating diseases related to lipid storage disorders, such as atherosclerosis and diabetes. In R1 represents hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl, R2 represents hydrogen, alkyl or halogen, R3 represents hydrogen or alkyl, R4 represents hydrogen, alkyl, hydroxy or alkoxy, R5 and R6 are chosen from hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl, A represents aryl or heterocyclyl, m equals 0-3, n equals 0-1, p equals 0-3, sum of m, n and p equals 1-4, the bond between carbon atoms Ca and Cb is a single or double carbon-carbon bond.

EFFECT: obtaining new biologically active compounds.

27 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with general formula (I) or pharmaceutically acceptable salts thereof, where R1 is chosen from a group containing optionally substituted C1-C6alkyl, lower alkoxy group, (lower)alkoxy(lower)alkyl, cycloalkyoxy(lower)alkyl, lower thioalkyl, (lower)alkylthio(lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R2 is chosen from a group containing optionally substituted (lower)alkyl, cycloalkyl, cycloalkyl(lower)alkyl; R3 is chosen from a group containing halogen, cyano group, optionally substituted (lower alkyl, lower thioalkyl, aryl, aryl(lower)alkyl, lower alkenyl, lower alkynyl); R4 is chosen from a group containing hydrogen, halogen, cyano group, hydroxyl group, optionally substituted (lower alkyl, lower alkoxy group, aryl, pyridyl, aryl(lower)alkyl, heteroaryl, which is an aromatic mono- or bicyclic hydrocarbon, containing from 5 to 9 ring atoms, from which one or more is a heteroatom, chosen from O, N or S, and an amino group) and a group, with formula R8-Z-(CH2)n-; where Z is a single bond or chosen from a group consisting of O, NH, CH2, CO, SO, SO2 or S; where R8 is chosen from a group containing optionally substituted (aryl, pyridyl); and where n=0, 1 or 2; R5 represents hydrogen; R6 is chosen from a group containing halogen, optionally substituted lower alkoxy group; R7 is one or more substitutes, independently chosen from a group containing hydrogen, optionally substituted lower alkoxy group; where the optional substitute or substitutes when R1-R8 are independently chosen from a group containing halogen, hydroxyl group, lower alkyl, mono- or di(lower)alkylamino group, aminocarbonyl, sulfinyl, sulfonyl, sulfanyl, mono- or di(lower)alkylaminocarbonyl, amino group, carboxyl group, lower alkoxy group, C3-C12cycloalkyl, (lower)alkylcarbonyl, (lower)alkoxycarbonyl, nitrile, aryl; all of which, except halogen, are independently optionally substituted with one or more substitutes, chosen from a group containing halogen, hydroxyl group, lower alkyl, sulfinyl, sulfonyl, sulfanyl, amino group, carboxyl group, lower alkoxy group, carbamoyl. Invention also relates to formula (I'), to a pharmaceutical composition, as well as use of formula (I) compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds, for preventing or treating bone diseases, associated with very low or resorption of calcium.

6 cl, 151 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds with formula I where R1, R2, R3 and Y together with a formula I residue, are compounds, chosen from a group given in the formula of invention, or to their pharmaceutically used and split esters, or to their acid-additive salts, which promote release of parathyroid hormone.

EFFECT: compounds can be used for making medicinal agents, with antagonistic properties towards calcium sensitive parathyroid gland receptor for treating diseases mediated by effect of parathyroid hormone.

7 cl, 179 ex

FIELD: chemistry.

SUBSTANCE: described are derivatives of pyridinecarboxamides with formula (I), where the descriptions of radicals are given in the formula of the invention and its salts.

EFFECT: compounds exhibit insecticide activity.

7 cl, 5 tbl, 21 ex

FIELD: chemistry.

SUBSTANCE: invention relates to (Z)-methyl-16-(5-oxo-2-phenyl-oxazol-4-ilidenmethyl)-15,16-epoxy-8(17),13(16),14-labdatrien-18-oate of formula (I) (I). Compound (I) possesses high antioxidative, hepatoprotective and hemostimulatng activity and can be used for correction of side effects, arising with introduction of highly toxic medications used in anti-tumor therapy.

EFFECT: obtaining compound, which possesses high antioxidative, hepatoprotective and hemostimulatng activity.

1 cl, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a combined product containing compounds of formula (I): where: R1 and R2 represent CF3; R3 and R4 represent fluoro; R5 and R6 represent hydrogen; R7 presents Cl, X represents CR8, where R8 represents Cl; and R9 represents NH2; or its veterinary acceptable salt, and b) doramectin. The invention also relates to an antiparasitic veterinary composition based on the said combined product.

EFFECT: obtaining a combined product which can be used in veterinary for treating parasitic infections in mammals.

4 cl, 1 dwg, 1 tbl, 37 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of formula (I) or to salts thereof: , where R1 is a hydrogen atom, amino group, R11-NH-, where R11 is a C1-6alkyl group, hydroxy-C1-6alkyl group, C1-6alkoxycarbonyl-C1-6alkyl group, R12-(CO)-NH-, where R12 is a C1-6alkyl group or C1-6alkoxy-C1-6alkyl group, C1-6alkyl group, hydroxy-C1-6-alkyl group, C1-6alkoxy group or C1-6alkoxy-C1-6alkyl group; R2 is a hydrogen atom, C1-6alkyl group, amino group or di-C1-6alkylamino group; one of X and Y represents a nitrogen atom, while the other represents a nitrogen or oxygen atom; ring A is a 5- or 6-member heteroaryl ring or benzene ring which can have 1 or 2 halogen atoms; Z is a single bond, methylene group, ethylene group, oxygen atom, sulphur atom, -CH2O-, -OCH2-, -NH-, -CH2NH-, -NHCH2-, -CH2S- or -SCH2-; R3 is hydrogen or a halogen atom, or C1-6alkyl group, C3-8cycloalkyl group, C6-10aryl group, 5- or 6-member heteroaryl group, where these groups can have 1 or 2 substitutes selected from a group of α substitutes: and [group of α substitutes] group of α substitutes is a group consisting of a halogen atom, cyano group, C1-6alkyl group, C1-6alkoxy group, C1-6alkoxycarbonyl group, C3-8cycloalkyl group, C1-6alkenyl group and C1-6alkynyl group; R4 is a hydrogen atom or halogen atom; except compounds in which all of R1, R2 and R4 represent a hydrogen atom while Z represents a single bond or R3 is a hydrogen atom; as well as a pharmaceutical composition and a medicinal agent with antifungal activity, based on these compounds, to an antifungal agent and use of formula I compounds for preparing an antifungal agent.

EFFECT: novel compounds with excellent antifungal effect are obtained and described.

36 cl, 228 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel benzyloxy-derivatives of general formula (I) , where R1 is a halogen; R2 is a 5-member heteroaryl group containing 2 or 3 heteroatoms selected from a group consisting of N, O or S, which can be substituted with R3, where R3 is a lower alkyl or -C(O)R; R is -NR'R" or lower alkoxy; R'/R" independently represent H; as well as to their pharmaceutically acceptable salts. Formula I compounds inhibit monoamine oxidase B.

EFFECT: compounds can be used for preparing a medicinal agent.

5 cl, 15 ex

FIELD: pharmacology.

SUBSTANCE: described are enantiomer-free compounds with a general formula of (1) wherein the R1, R2, R3, R4 and X- residue may have as specified in the invention formula, intermediary compounds, a pharmaceutical composition as well as their application in the capacity of medications intended for respiratory tract diseases treatment.

EFFECT: new enantiomer-free b-agonists, their preparation method and application in the capacity of medications.

11 cl, 5 dwg, 3 tbl, 37 ex

FIELD: medicine.

SUBSTANCE: invention is related to new derivatives of aryl and heteroarylpiperidinecarboxylates, of formula (I): , where: type means integer numbers from 1 to 3, such that m+n is integer number from 2 to 5; p means integer number from 1 to 7; A means simple connection or is selected from one or several groups X, Y; X means -CH2-; Y means C2-alkynilene group; R1 means group R5, substituted with one or several groups R6 and/or R7; R2 means H, F, OH; R3 means H; R4 means H, C1-6-alkyl; R5 means group selected from phenyl, pyridinyl, pyrimidinyl, pyrrolyl, imidazolyl, thiazolyl, pyrazolyl, isoxazolyl, oxadiazolyl, naphthyl, chinolynyl, tetrahydrochinolinyl, isochinolinyl, tetrahydroisochinolinyl, indolyl, indolinyl, isoindolyl, benzimidazolyl, benzoxazolyl, benzizoxazolyl, benzothiazolyl, benzithiazolyl, benzotriazolyl, benzoxadiazolyl, pyrrolopyridinyl; R6 means halogen, CN, C1-6-alkyl, C3-7-cycloalkyl, C1-6-alkoxy, OH, C1-6-fluoroalkyl, C1-6-fluoroalkoxy, or cycle selected from pyrrolidine and piperidine cycle, besides this cycle is unnecessarily substituted with C1-6-alkyl group; R7 means phenyl group, besides group or groups R7 may be substituted with one or several groups R6, identical or differing from each other, selected from halogen, C1-6-alkyl and C1-6-fluoroalkyl, C1-6-alkoxy, in the form of pharmaceutically acceptable base or acid-additive salt.

EFFECT: compounds are applicable as inhibitors of FAAH ferment.

10 cl, 1 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: invention is related to new heterocyclic compounds of common formula (I), and also their pharmaceutically acceptable salts, hydrates and/or solvates, possessing properties of human neutrophil elastase. In common formula (I) , A means phenyl or pyridyl cycle, R1 and R3 each means atom of hydrogen, R2 means atom of fluorine, chlorine, bromine, nitro group or cyano group, R4 means cyano group, alkyl carbonyl group with number of carbon atoms in alkyl residue from one to four, or alkoxycarbonyl group with number of carbon atoms in alkoxyl residue from one to four, besides alkoxycarbonyk group with number of carbon items in alkoxyl residue from one to four, may be substituted with substituent, which is selected from the group that includes hydroxyl group, alkoxygroup with number of carbon atoms from one to four, alkoxycarbonyl group with number of carbon atoms in alkoxyl residue from one to four, mono- or dialkylaminogroup, with number of carbon atoms in each of alkyl residues from one to four, 5-6-member heteroaryl group, which contains from 1 to 4 heteroatoms in heteroaryl ring, selected from nitrogen, oxygen or sulfur, possibly susbstituted with alkyl group, which contains from 1 to 4 atoms of carbon and possibly condensed with benzene ring, and 5-8 member heterocyclyl group, which contains from 1 to 3 heteroatoms from group of nitrogen, oxygen or sulfur, or SO, SO2 possibly substituted with ketogroup, R5 means methyl group, R6 means atom of hydrogen, alkyl group with number of carbon atoms from one to four, mono- or dialkylaminocarbonyl group with number of carbon atoms in each of alkyl residues from one to four, etc., Y1, Y2, Y3, Y4 and Y5 each means CH-group. Invention is also related to pharmaceutical composition.

EFFECT: possibility of application for treatment of chronic obstructive lung diseases, acute coronary syndrome, acute myocardial infarction and progressing cardiac decompensation.

8 cl, 1 dwg, 111 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 2-heteroaryl derivatives of benzothiazole and benzoxazole of formula by boiling amine with general formula with acid chloride of general formula , where R=2-furyl or 2-thienyl, X = S or O, in 1-methyl-2-pyrrolidone.

EFFECT: method increases output of product to 78 to 90% and environmental friendliness of the process.

1 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I-a), where R1 and R2, each independently, represent -COORA (where RA is hydrogen or C1-8 alkyl), -CONRBSO2RC (where RB is hydrogen or C1-8 alkyl, RC is C1-8 hydrocarbon), -D-R1 is -CO-(CH2)2-R1, -CO-(CH2)3-R1, -CO-(CH2)4-R1 or C1-4alkylene-R1; E is a bond or C1-4alkylene; ring formula represents a 3,4-dihydro-2H-1,4-benzoxazine or 1H-indole ring; V is , where R110 is hydrogen or C1-8 alkyl, and the arrow shows that it is bonded to ring A; the group with formula is a phenyl group, which can contain a group with formula , where ring 2 is a C5-10 mono- or bicyclic aromatic carbocyclic ring, which can be partially or completely saturated, spirobicyclic carbocyclic ring, or a carbocyclic ring bonded by a bridge bond; where W is -O-CH2-, -O-(CH2)2, -O-(CH2)3, -O-(CH2)4, -O-(CH2)5, -CH2-O, -(CH2)2-O-, -(CH2)3-O-, -(CH2)4-O-, -(CH2)5-O-, -O-(CH2)3-O-, -O-(CH2)4-O-, -O-(CH2)5-O-, C1-6 alkylene, its N-oxide, its salt or its solvate. The invention also relates to a pharmaceutical composition based on formula I-a compound and its use.

EFFECT: obtaining new derivatives of benzoxazine and indole, with antagonistic effect on cysLT2 and which are useful for preventing and/or curing respiratory diseases, such as bronchial asthma, chronic obstructive lung diseases.

8 cl, 57 tbl, 261 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new benzimidazole derivatives with general formula (I), where A represents -CH2-, -C(O), -C(O)-C(Ra)(Rb)-, X represents a -CH- radical; Ra and Rb independently represent a hydrogen atom or (C1-C6)alkyl radical; R1 represents a hydrogen atom or (C1-C8)alkyl radical; R2 represents a (C1-C8)alkyl radical; R3 represents -(CH2)P-Z3, -C(O)-Z'3 or -C(O)-NH-Z"3; Z3 represents (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkoxy, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkyl-N(RN)carbonyl, (C3-C7)cycloalkyl, aryl, arylthio or heteroaryl radical, Z3 is bonded to the -(CH2)P- through a carbon atom, heteroaryl radical, which is a 5-10- member heteroaryl, which contains 1-2 identical or different heteroatoms, chosen from sulphur, nitrogen or oxygen, and optionally substituted with one or more identical or different substitutes, chosen from halogen, nitro group or -(CH2)P'-V30-Y3; aryl radical, chosen from phenyl or naphthyl, optionally substituted with one or more identical or different substitutes, chosen from halogen, nitro group, cyano group, (C2-C6)alkenyl, pyrrolidinyl, phenyl, phenyloxy, phenylalkyloxy, 5-7- member heteroaryl, containing 1-3 nitrogen atoms and -(CH2)p'-V31-Y3; V30 represents -O-, -C(O)-, -C(O)-O- or a covalent bond; V31 represents -O-, -S-, -SO2-, -C(O)-, -C(O)-O-, -N(RN)-, -NH-C(O)- or a covalent bond; Y3 represents a hydrogen atom or (C1-C6)alkyl radical, optionally substituted with one or more identical or different halogen radicals; RN represents a hydrogen atom or (C1-C6)alkyl radical; Z3 represents a radical with a given formula (see below); Z'3 represents a phenyl radical, optionally substituted with one ore more identical or different substitutes, chosen from -(CH2)P"-V'3-Y'3; V'3 represents -O-; Y'3 represents a hydrogen atom or (C1-C6)alkyl radical; Z"3 represents a hydrogen atom or -(CH2)q-A"3 radical; A"3 represents (C1-C6)alkyl, phenyl or thienyl radical; alkyl or phenyl radical can be optionally substituted with one or more identical or different substitutes, chosen from halogen and -V"3-Y"3; V"3 represents -O-, -C(O)-, -C(O)-O- or a covalent bond; Y"3 represents a hydrogen atom or (C1-C6)alkyl radical; p is an integer from 0 to 6; p' and p" independently represent an integer from 0 to 1; q is an integer from 0 to 2; R4 represents a radical with formula -(CH2)S-R'4; R'4 represents a 5-7- member heterocycloalkyl, containing at least one nitrogen atom and optionally substituted with (C1-C6)alkyl; or a radical with formula -NW4W'4; W4 represents a hydrogen atom; W'4 represents a hydrogen atom; s is an integer from 0 to 6; in racemic or enantiomeric form or any combination of the said forms, or its pharmaceutically acceptable salt. The invention also relates to a method of obtaining a compound in paragraph 1, a pharmaceutical composition based on the said compound and its use in making a medicinal agent.

EFFECT: new benzimidazole derivatives have good affinity to certain subtypes of melanocortin receptors.

26 cl, 8 ex

FIELD: pharmacology.

SUBSTANCE: described are enantiomer-free compounds with a general formula of (1) wherein the R1, R2, R3, R4 and X- residue may have as specified in the invention formula, intermediary compounds, a pharmaceutical composition as well as their application in the capacity of medications intended for respiratory tract diseases treatment.

EFFECT: new enantiomer-free b-agonists, their preparation method and application in the capacity of medications.

11 cl, 5 dwg, 3 tbl, 37 ex

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