Tetrahydropyranochromen gamma-secretase inhibitors

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new gamma-secretase inhibitors of formula I: , wherein L1,R1, R2,X,n and Ar have the values specified in the description, their pharmaceutically acceptable salts and solvates, as well as to pharmaceutical compositions based on these compounds for treating Alzheimer's disease and the use of drugs for gamma-secretase and beta-amyloid protein inhibition, and for treating neurodegenerative diseases such as Alzheimer's disease.

EFFECT: preparing the compound for treating the neurodegenerative diseases.

38 cl

 

The text descriptions are given in facsimile form.

1. The compound of the formula

or its pharmaceutically acceptable salt or MES, where:
X is selected from the group consisting of Oh and CH2;
R1selected from the group consisting of: (1) -alkylen-S(O)2-(C1-C6)alkyl, (2) -alkylen-S(O)2-(C1-C6)halogenoalkane; (3) alkylen-S(O)2-R6, (4) -alkylen-S(O)2-R6, (5) -alkylen-S(O)2-substituted(C1-C6)alkyl, (6) -alkylene-(tetrahydrothiophene 1,1-dioxide), (7) -alkenyl-S(O)2-(C1-C6)alkyl and (8) -cycloalkyl-S(O)2-(C1-C6)alkyl;
where this is alkylen-S(O)2-substituted(C1-C6)alkyl group, R1substituted by one or more substituents independently selected from the group sotoyama is from: HE, atom of halogen, -CF3, -O-(C1-C6)alkyl and-O-(halo(C1-C6)alkyl);
R2selected from the group consisting of: H and alkyl;
R6selected from the group consisting of: (1) phenyl, (2) furil;
R8is cycloalkyl;
Ar is selected from the group consisting of: (1) unsubstituted phenyl, (2) phenyl substituted by one or more groups L1A, (3) unsubstituted heteroaryl;
each L1independently selected from the group consisting of: halogen atom and a halogen(C1-C6)alkyl;
each L1Aindependently selected from the group consisting of: halogen atom, alkyl, -CN, -CF3, -O-(C1-C6)alkyl, -O-(halo(C1-C6)alkyl), halogen(C1-C6)alkyl and-S(O)2(C1-C6)alkyl; and
n is 0, 1, 2, or 3.

2. The compound according to claim 1, having the formula


3. The compound according to claim 2:
(a) selected from the group consisting of compounds of formulas (Ii)to(Ivii), where n is 2, each L1represents identical or different halogen atoms, and these groups L1linked to the phenyl fragment as shown in the formula (IIA)

(b) selected from the group consisting of compounds of formulas (Ii)to(Ivii), where n is 2, each L1represents Diakonie or different halogen atoms, and these groups L1linked to the phenyl fragment as shown in the formula (IIA)

where each L1is a F.

4. The compound according to claim 2, where:
(a) the specified connection selected from the group consisting of compounds of formulas (Ii)to(Ivii), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl; or
(b) specified compound selected from the group consisting of compounds of formulas (Ii)to(Ivii), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl; or
(C) the specified connection selected from the group consisting of compounds of formulas (Ii)to(Ivii), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2 SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl, and where these groups L1represent F.

5. The compound according to claim 1, having the formula

6. The compound according to claim 5:
(a) selected from the group consisting of compounds of formulas (I.A1a)-(I.A1h), where n is 2, each L1represents identical or different halogen atoms, and these groups L1linked to the phenyl fragment as shown in the formula (IIA)

(b) selected from the group consisting of compounds of formulas (I.A1a)-(I.A1h), where n is 2, each L1represents identical or different halogen atoms, and these groups L1linked to the phenyl fragment as shown in the formula (IIA)

where each L1is a F.

7. The compound according to claim 5, where:
(a) the specified connection selected from the group consisting of compounds of formulas (I.A1a)-(I.A1h), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2(b) specified compound selected from the group consisting of compounds of formulas (I.A1a)-(I.A1h), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl, and where each L1represents identical or different halogen atoms.

8. The connection according to claim 7, where the groups of the L1represent F.

9. The connection of claim 8, where: Ar represents a p-Cl-phenyl-; or Ar represents a p-CN-phenyl-; or Ar represents a p-CF3is phenyl; or
Ar represents a p-CH3CH2SO2phenyl; or Ar represents a p-Br-phenyl; or Ar is a m,p-di-F-phenyl; or Ar is a m,p-di-CN-phenyl; or Ar represents a p-CH3O-phenyl; or Ar represents a p-CF3CH2Opener.

10. The connection according to claim 6, where: (a) R2represents H; or R2represents alkyl; or R2represents methyl.

11. The connection of claim 8, where: (a) R2represents H; or R2represents alkyl; or
R2represents methyl.

12. The compound according to claim 1, having the formula

13. Connection para.12:
(a) selected from the group consisting of compounds of formulas (I.A2a)-(I.A2h), where n is 2, each L1represents identical or different halogen atoms, and these groups L1linked to the phenyl fragment as shown in the formula (IIA)

(b) selected from the group consisting of compounds of formulas (I.A2a)-(I.A2h), where n is 2, each L1represents identical or different halogen atoms, and these groups L1linked to the phenyl fragment as shown in the formula (IIA)

where each L is a F.

14. The connection section 12, where:
(a) the specified connection selected from the group consisting of compounds of formulas (I.A2a)-(I.A2h), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl; or
(b) specified compound selected from the group consisting of compounds of formulas (I.A2a)-(I.A2h), where n is equal to 2, and group L1linked to the phenyl fragment as shown in (IIA)
15. The connection 14, where the groups of the L1represent F.

16. The connection indicated in paragraph 15, where: Ar represents a p-Cl-phenyl-; or Ar represents a p-CN-phenyl-; or Ar represents a p-CF3is phenyl; or Ar represents a p-CH3CH2SO2phenyl; or Ar represents a p-Br-phenyl; or Ar is a m,p-di-F-phenyl; or Ar is a m,p-di-CN-phenyl; or Ar represents a p-CH3O-phenyl; or Ar represents a p-CF3CH2Opener.

17. The connection indicated in paragraph 13, where: R2represents H; or R2represents alkyl; or R2represents methyl.

18. The connection indicated in paragraph 15, where: R2represents H; or R2represents alkyl; or R2represents methyl.

19. The compound according to claim 1, where
(a) R1selected from the group consisting of











(b) R1selected from the group consisting of











20. The connection according to claim 19 where the compound of formula (I) is a compound selected from the group consisting of compounds of formulas (Ii), (Iii), (Iiii), (Iiv), (I.A1b), (I.A1c), (I.A1d), (I.A2b), (I.A2c) or (I.A1d); and where R1selected from the group consisting is she from











21. Connection claim 20, where:
(a) n is 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl; or
(b) n is 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl, and where each 1represents identical or different halogen atoms.

22. Connection item 21, where the groups of the L1represent F.

23. Connection p.22, where: R2represents H; or R2represents alkyl; or R2represents methyl.

24. Connection p.22 where:
(a) R2represents H, and Ar represents a p-Cl-phenyl-; or
(b) R2represents H, and Ar represents a p-CN-phenyl-; or
(c) R2represents H, and Ar represents a p-CF3-phenyl-; or
(d) R2represents H, and Ar represents a p-CH3CH2SO2phenyl-; or
(e) R2represents H, and Ar represents a p-Br-phenyl-; or
(f) R2represents H, and Ar is a m,p-di-F-phenyl-; or
(g) R2represents H, and Ar is a m,p-di-CN-phenyl-; or
(h) R2represents H, and Ar represents a p-CH2O-phenyl-; or
(i) R2represents H, and Ar represents a p-CF3CH2O-phenyl-.

25. Connection p.22 where:
(a) R2represents methyl, and Ar represents a p-Cl-phenyl-; or
(b) R2represents methyl, and Ar represents a p-CN-phenyl-; or
(c) R2represents methyl, and Ar represents a p-CF3-phenyl-; or
(d) R2PR is dstanley a methyl, and Ar represents a p-CH3CH2SO2-phenyl-; or
(e) R2represents methyl, and Ar represents a p-Br-phenyl-; or
(f) R2represents methyl, and Ar is a m,p-di-F-phenyl-; or
(g) R2represents methyl, and Ar is a m,p-di-CN-phenyl-; or
(h) R2represents methyl, and Ar represents a p-CH3O-phenyl-; or
(1) R2represents methyl, and Ar represents a p-CF3CH2O-phenyl-.

26. The compound according to claim 1, where R1selected from the group consisting of:











27. Connection p, where the compound of formula (I) selected from the group consisting of compounds of formulas (Iv), (Ivi), (Ivii), (I.A1f), (I.A1g), (I.A1h), (I.A2f), (I.A2g) and (I.A2h).

28. With the Association according to item 27, where:
(a) n is 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl; or
(b) n is 2, and group L1linked to the phenyl fragment as shown in (IIA)

and Ar is selected from the group consisting of p-Cl-phenyl-, p-CN-phenyl-, p-CF3-phenyl, p-CH3CH2SO2phenyl, p-Br-phenyl, m,p-di-F-phenyl, m,p-di-CN-phenyl, p-CH3O-phenyl, p-CF3CH2Openil and pyridyl, and where each L1represents identical or different halogen atoms.

29. Connection p, where these groups L1represent F.

30. The connection clause 29, where: R2represents H; or R2represents alkyl; or R2represents methyl.

31. Connection article 30 where:
(a) R2represents H, and Ar represents a p-Cl-phenyl-; or
(b) R2represents H, and Ar represents a p-CN-phenyl-; or
(c) R2represents H, and Ar represents a p-CF3-phenyl-; or
(d) R2represents H, and Ar represents a p-CH3CH2SO2phenyl-; Il the
(e) R2represents H, and Ar represents a p-Br-phenyl-; or
(f) R2represents H, and Ar is a m,p-di-F-phenyl-; or
(g) R2represents H, and Ar is a m,p-di-CN-phenyl-; or
(h) R2represents H, and Ar represents a p-CH3O-phenyl-; or
(i) R2represents H, and Ar represents a p-CF3CH2O-phenyl-.

32. Connection article 30 where:
(a) R2represents methyl, and Ar represents a p-Cl-phenyl-; or
(b) R2represents methyl, and Ar represents a p-CN-phenyl-; or
(c) R2represents methyl, and Ar represents a p-CF3-phenyl-; or
(d) R2represents methyl, and Ar represents a p-CH3CH2SO2phenyl-; or
(e) R2represents methyl, and Ar represents a p-Br-phenyl-; or
(f) R2represents methyl, and Ar is a m,p-di-F-phenyl-; or
(g) R2represents methyl, and Ar is a m,p-di-CN-phenyl-; or
(h) R2represents methyl, and Ar represents a p-CH3O-phenyl-; or
(i) R2represents methyl, and Ar represents a p-CF3CH2O-phenyl-.

33. The compound according to claim 1, selected from the group consisting of the following compounds


























and

34. The compound according to claim 1, selected from the following MES compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-), 80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p.

35. Pharmaceutical composition for treating Alzheimer's disease, containing an effective amount of at least one compound according to claim 1 and at least one pharmaceutically acceptable carrier.

36. Pharmaceutical composition for treating Alzheimer's disease, comprising:
(a) an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier; or
(b) an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier, where the specified connection selected from the group of the following compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-), 80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p; or
(c) effect and the number of compounds according to claim 1 and a pharmaceutically acceptable carrier, where the specified connection is a MES compounds selected from the group of the following compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-), 80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p.

37. The application of one or more compounds according to claim 1 for the production of medicines:
(a) for inhibition of gamma-secretase; or
(b) inhibition of gamma-secretase, where these compounds selected from the group of the following compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-), 80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p; or
(c) for treating one or more neurodegenerative diseases;
(d) for treating one or more neurodegenerative diseases, where these compounds selected from the group of the following compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-)80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p; or
(e) for inhibiting the deposition of beta-amyloid protein; or
(f) for inhibiting the deposition of beta-amyloid protein, which indicated the s compounds selected from the group of the following compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-), 80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p.

38. The application of one or more compounds according to claim 1 for the production of medicines:
(a) for the treatment of Alzheimer's disease; or
(b) for the treatment of Alzheimer's disease, where these compounds selected from the group of the following compounds 12, 13, 22A-22N, 22B-rat, 26A, 26C, 27, 28, 31, 33(-), 36, 37, 39, 44A, V, 55-57, 60, 70A, 71A(-), 75A-rat, 75V(-), 76A(-), 76A(+), V(-), 78A(-), 79A(-), 80A(-), A-rat, A(-), A(+), V(-), A, 83A, A, 85A, 85B(-), 86A, B, V-rat, V(-), V(+), 106(-), 107(-), 108(-) and 111(-)presented in p.

39. The compound of formula 22A or MES



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) or to their pharmaceutically acceptable salts, in which X is selected from group, consisting of-C(R1)2-, -O-, -S-, -S(O2)-, -NR1-; each R1 is independently selected from group consisting of H and alkyl; each of R2, R3 and R4 is independently selected from group consisting of (1) H, (2) alkyl, (3) -OR5, (4) alkylene-OR5, (5) -alkylene-R6, (6) -C(O)O-alkyl, (7) - alkylene-C(O)O-alkyl, (8) -alkylene-R8, (9) -NHR5, (10) -N(R5)2, (11) alkenyl, (12) -NH-R8, (13) -NH-CH(C(O)O(C1-C6)alkyl)-alkylene-O-alkyleneR6, (14)-NHCH(C(O)O(C1-C6)aalkyl)-alkylene-OH, (15) -NH-C(O)-alkenyl and (16) -N(C1-C6alkyl)C(O)-alkenyl; or R2 and R3 or R2 and R4 or R3 and R4 together with atoms with which they are bound, form condensed 3-7-member cycloalkyl or heterocycloalkyl ring, which represents non-aromatic monocyclic ring system, which contains in ring from about 5 to about 7 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen or oxygen, and said condensed cycloalkyl or heterocycloalkyl ring is not substituted or is substituted with one or several groups L3 ; and on condition that if X represents -O-, and m equals 1, then, at least, one of R2, R3 or R4 is not H; each R5 is independently selected from group consisting of (1) H, (2) (C1-C6)alkyl, (3) hydroxy-substituted alkyl, (4) R6, (5) R7, (6) -C(O)-(C1-C6)alkyl, (7) -C(O)-(C1-C6)halogenalkyl, (8) -C(O)-R6, (9) -C(O)-R7, (10) -C(O)NH-(C1-C6)alkyl, (11) -C(O)N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (12) -S(O)2-(C1-C6)alkyl, (13) -S(O)2-(C1-C6)halogenalkyl, (14) -S(O)2-R6, (15) -S(O)2-R7, (16) -S(O)2-R8, (17) -alkylene-C(O)-(C1-C6)alkyl, (18) -alkylene-C(O)-(C1-C6)halogen-alkyl, (19) -alkylene-C(O)-R6, (20) -alkylene-C(O)-R7, (21) -alkylene-S(O)2-(C1-C6)alkyl, (22) -alkylene-S(O)2-(C1-C6)halogenalkyl, (23) -alkylene-S(O)2-R6, (24) -alkylene-S(O)2-R7, (25) -alkylene-S(O)2-R8, (26) -alkylene-NHC(O)-(C1-C6)alkyl, (27) -alkylene-NHC(O)-(C1-C6)halogenalkyl, (28) alkylene-NHC(O)-R6, (29) -alkylene-NHC(O)-R7, (30) -alkylene-NHS(O)2-(C1-C6)alkyl, (31) -alkylene-NHS(O)2-(C1-C6)halogenalkyl, (32) -alkylene-NHS(O)2-R6, (33) -alkylene-NHS(O)2-R7, (34) -alkylene-N(alkyl)C(O)-(C1-C6)alkyl, (35) -alkylene-N(alkyl)C(O)-(C1-C6)halogenalkyl, (36) -alkylene-N(alkyl)C(O)-R6, (37) -alkylene-N(alkyl)C(O)-R7, (38) -alkylene-N(alkyl)S(O)2-(C1-Ce)alkyl, (39) -alkylene-N(alkyl)S(O)2-(C1-C6)halogen-alkyl, (40)-alkylene-N(alkyl)S(O)2-R6, (41) -alkylene-N(alkyl)S(O)2-R7, (42) -alkylene-C(O)-NH-(C1-C6)alkyl, (43) -alkylene-C(O)-NHR6, (44) -alkylene-C(O)-NHR7, (45) -alkylene-S(O)2NH-(C1-C6)alkyl, (46) -alkylene-S(O)2NH-R6, (47) -alkylene-S(O)2NH-R7 , (48) -alkylene-C(O)-N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (49) -alkylene-C(O)-N(alkyl)-R6, (50) -alkylene-C(O)-N(alkylene)-R7, (51) -alkylene-S(O)2N((C1-C6)alkyl)2, in which each alkyl group is selected independently, (52) -alkylene-S(O)2N(alkyl)-R6, (53) -alkylene-S(O)2N(alkyl)-R7, (54) -alkylene-OH, (55) -alkylene-OC(O)-NH-alkyl, (56) -alkylene-OC(O)NH-R8, (57) -alkylene-CN, (58) -R8, (59) -alkylene-SH, (60) -alkylene-S(O)2-NH-R8, (61) -alkylene-S(O)2-alkylene-R6, (62) substituted with halogen alkylene, (63) -C(O)OR8, (64) -C(O)O(C1-C6)alkyl, (65) -C(O)R8, (66) -C(O)-alkylene-O-(C1-C6)alkyl, (67) -C(O)NH2, (68) -alkylene-O-(C1-C6)alkyl, (69) -alkylene-R8, (70) -S(O)2-halogen(C1-C6)alkyl, (71) hydroxy-substituted halogen(C1-C6)alkyl, (72) -alkylene-NH2, (73) -alkylene-NH-S(O)2-R8, (74) -alkylene-NH-C(O)-R8, (75) -alkylene-NH-C(O)O-(C1-C6)alkyl, (76) -alkylene-O-C(O)-(C1-C6)alkyl, (77) -alkylene-O-S(O)2-(C1-C6)alkyl, (78) -alkylene-R6 , (79) -alkylene-R7, (80) -alkylene-NH-C(O)NH-(C1-C6)alkyl, (81) -alkylene-N(S(O)2 halogen(C1-C6)alkyl)2, and each -S(O)2 halogen(C1-C6)alkyl fragment is selected independently, (82) -alkylene-N((C1-C6)alkyl)S(O)2-R8 , (83) -alkylene-OC(O)-N(alkyl)2, and each alkyl is selected independently, (84) -alkylene-NH-(C1-C6)alkyl, (85) -C(O)-alkylene-C(O)O-(C1-C6)alkyl, (86) -C(O)-C(O)-O-(C1-C6)alkyl, (87) -C(O)-alkylene-R6, (88) -C(O)-NH-R8, (89) -C(O)-NH-R6, (90) -C(O)-NH-alkylene-R6, (91) -C(O)-alkylene-NH-S(O)2-halogen(C1-C6)alkyl, (92) -C(O)-alkylene-NH-C(O)-O-(C1-C6)alkyl, (93) -C(O)-alkylene-NH2, (94) -C(O)-alkylene-NH-S(O)2-R8, (95) -C(O)-alkylene-NH-S(O)2-(C1-C6)alkyl, (96) -C(O)-alkylene-NH-C(O)-(C1-C6)alkyl, (97) -C(O)-alkylene-N(S(O)2(C1-C6)alkyl)2, and each -S(O)2(C1-C6)alkyl fragment is elected independently, (98) -C(O)-alkylene-NH-C(O)-NH-(C1-C6)alkyl, (99) -alkylene-O-R6, (100) -alkylene-R7, (101) -C(O)OH, (102) -alkylene-N(S(O)2(C1-C6)alkyl)2, (103) -alkylene-C(O)-O-(C1-C6)alkyl, (104) halogenalkyl, (105) halogen, (106) -alkylene-C(O)-NH2, (107) =N-O-(C1-C6)alkyl, (108) =N-O-alkylene-R6, (109) =N-O-alkenyl, (110) -N-O-R6, (111) =N-NH-S(O)2-R6, (112) alkenyl, (113) =R8, (114) -O-C(O)-R9, (115) -O-C(O)-(C1-C6)alkyl, (116)-CN, R6 is selected from group consisting of unsubstituted (C6-C14)aryl, (C6-C14)aryl, substituted with one or several groups L1, unsubstituted (C5-C14)heteroaryl and (C5-C14)heteroaryl, which represents aromatic monocyclic or bicyclic system, which contains in ring from about 5 to about 9 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen or sulphur, one or in combination, substituted with one or several groups L1; R7 is selected from group consisting of unsubstituted heterocycloalkyl and heterocycloalkyl which represents non-aromatic monocyclic system, which contains in ring from about 4 to about 6 atoms, and one or several atoms in ring system represent atom of element, different from carbon, for instance, nitrogen, oxygen substituted with one or several groups L2; R8 is selected from group consisting of unsubstituted cycloalkyl and cycloalkyl substituted with one or several groups L2; A8 is selected from group consisting of (a) unsubstituted aryl, (b) aryl substituted with one or several groups L1; each group L1 is independently selected fron group consisting of halogen, alkyl, -CN, -CF3, -O-(C1-C6)alkyl, -O-(halogen(C1-C6)alkyl), -alkylen-OH (-CH2OH); each group L2 is independently selected from group consisting of (a) -OH, (b) alkyl, (c) alkyl substituted with one or several groups -OH and (d) piperidyl; each group L3 is independently selected from group consisting of -CN, =O, R5 , -OR5 ; =N-R5 and -N(R5)2; n equals 0, 1, 2 or 3; and m equals 0, 1 or 2; and on condition that in composition of substituent -OR5 fragment R5 and oxygen atom, which it is bound with, do not form group -O-O-; and on condition that in composition of substituents -OR5, =N-R5 and -NHR5 R5 are not -CH2OH, -CH2NH2, -CH2NH-alkyl, -CH2NH-aryl or -C(O)OH. Invention also relates to pharmaceutical composition, as well as to application of one or several compounds by one of ii. 1-125.

EFFECT: obtaining novel biologically active compounds possessing properties of γ-secretase inhibitor.

127 cl, 447 ex, 94 tbl

FIELD: agriculture.

SUBSTANCE: improvement of effectiveness of insecticidal preparation is achieved through the use in sublethal doses of a mixture of fluorinated usnic acid (FUA) of the formula and II obtained by the reaction of (+)-usnic acid with perfluoropropene as a synergist of such insecticides. The decline of the latent period of the disease and increased mortality rate of larvae of Colorado potato beetle is marked using FUA and entomopathogenic microorganisms of Beauveria bassiana, Metarhizium anisopliae and Bacillus thuringiensis. The mixed composition of FUA at a concentration of 0.03% with a suspension of conidia of the fungus Bauveria bassiana with a titer of 3×106 conidia/ml (in vitro) and 5×106 conidia/ml (in the field) has proved to be the best in all respects.

EFFECT: increased biological efficiency of insecticides based on entomopathogenic fungi and bacteria.

1 cl, 4 tbl,5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing an optically active chromene oxide compound of formula or formula where R5, R6, R7, R8, R9, R10 and A are as described in the claim, and the absolute configuration of carbon atoms, denoted by *, denotes (R) or (S), which includes asymmetric epoxidation of a chromene compound of formula or formula with an oxidant in a solvent using optically active titanium complexes of formula formula formula and formula where R1, R2, R3 and R4 are defined in the claim, as a catalyst for asymmetric oxidation of the optically active chromene compound with high enantioselectivity and high chemical output.

EFFECT: efficient method of producing an optically active chromene oxide compound, which is an important intermediate compound used to produce a benzopyran compound, which is effective in treating arrhythmia.

18 cl, 26 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) (lb) in which A denotes a benzene ring; Ar denotes naphthalenyl which optionally contains 1-3 substitutes independently selected from a group comprising C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, hydroxy group, C1-C6alkoxy group, halogen, heteroalkyl, heteroalkoxy group, nitro group, cyano group, amino- and mono- or di- C1-C6alkyl-substuted amino group; R1 denotes hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy group, carboxy group, heteroalkyl, hydroxy group optionally substituted with heterocyclylcarbonyl-C1-C6alkyl or R1 denotes N(R')(R")-C1-C6alkyl or N(R')(R")-carbonyl- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C6alkyl, heteroalkyl, phenyl-C1-C6alkyl; or R1 denotes R'-CO-N(R")-C1-C6alkyl, R'-O-CO-N(R")- C1-C6alkyl- or R'-SO2-N(R")- C1-C6alkyl-, in which R' and R" are independently selected from a group comprising hydrogen, C1-C6alkyl, C3-C7cyclalkyl, C3-C7cycloalkyl- C1-C6alkyl or optionally substituted phenyl; R2, R2' and R2" independently denote hydrogen, halogen, cyano group, C1-C6alkyl, halogenated C1-C6alkyl or C1-C6alkoxy group; n equals 1; and pharmaceutically acceptable salts thereof. The invention also relates to use of compounds in any of claims 1-9, as well as to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds with chymase inhibiting activity.

14 cl, 128 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula formula (1) formula (2) or to their hydrate, solvate, salt or tautomer form where R1 independently represents H or halogen; R2 represents H or --R10-NR11R12 where R10 represents C1-C6 alkylene; R11 and R12 independently represent H, C1-C4 alkyl; and R3 independently represents H or halogen. Besides, the invention covers methods of preparing the compounds of the present invention.

EFFECT: new compounds which can find application for preparing the compounds applicable for treatment or prevention of cardiac arrhythmia.

6 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or stereoisomer thereof, or salt thereof, as well as synthesis method thereof and intermediate compounds of formulae (II) and (III) used in this method.

EFFECT: novel compound which can be used to produce HIV protease inhibitors.

23 cl, 2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel amino compound of formula: where X is S or O; R1 and R2 independently denote H or C1-4alkyl, or R1 and R2 together with the nitrogen atom with which they are bonded form a 5- or 6-member heterocyclic ring; and n equals 1 or 2, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the compound as an active ingredient, and use of the amino compound or pharmaceutically acceptable salt thereof to produce a drug for treating depression.

EFFECT: improved method.

8 cl, 4 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: present invention refers to the field of organic chemistry, notably to derivatives of dihydroimidazole with the general formula (I) and to its pharmaceutically acceptable salts where X1 and X2 denote halogen; R1 and R2 are chosen from the group including -H, -CH3, -CH2CH3 on the condition that both R1 and R2 do not denote hydrogen; R3 denotes -H or -C(=O)-R7; and if R6 denotes hydrogen, then R4 denotes -OCH3, -OCH2CH3 or -OCH(CH3)2; R5 denotes -H, - halogen, -CF3, -OCH3, -C(CH3)2, - cyclopropyl, - cyano group, -C(CH3)3, -C(CH3)2OR (where R denotes -H), -C(CH3)2CH-OR (where R denotes -CH3), -C(CH3)2CN, -C(CH3)2COR (where R denotes -CH3), -SR (where R denotes -CH2CH3) or -SO2R (where R denotes -CH3, -CH2CH3, 1-pyrrolidine, -NH-tert-butyl); and if R6 does not denote hydrogen, then R4 denotes -OCH2CH3; R5 denotes hydrogen, -Cl, -OCH3, tert butyl; R6 denotes -Cl, cyclopropyl, -SO2R (where R denotes -CH3, 1-pyrrolidine, -NH-tert-butyl or -N(CH3)2); and R7 is chosen from the group including i) -CH3, -CH(CH3)2, -CH2CH(CH3)2, cyclopropyl, cyclobutyl, -CH2CH2Ph, 2-furanyl, phenyl or phenyl substituted with chlorine, -OCH3 or cyano group, ii) 1-piperidinyl, iii) -NRc2 (where Rc denotes -CH2CH2OH, -CH2CH2OCH3 or -CH2CH(OH)CH2OH, iv) substituted piperazidine with the formula where R is chosen from the group including a) hydrogen, c) -CH(CH3)2, k) -CH2CH2Rd (where Rd denotes -OH, -OCH3, -CF3, -SO2CH3, -NH2, -NHCOCH3, -NHSO2CH3, 4-morfolinil, 2-izotiazolidinil-1, 1-dioxide), l) -CH2CH2CH2Re (where Re denotes -OCH3, -SO2CH3, -SO2CH2CH3, -CN), m) -CH2-CO-Rh (where Rh denotes -NH2, 1-pyrrolidinyl, 4-morfolinil), n) -SO2Ri (where Ri denotes -CH3, -CH2CH3), o) -CORj (where Rj denotes -CH3, 2-tetrahydrofuranyl, -NH2, -N(CH3)2), p) 4-tetrahydro-2H-thiopiranyl-1,1-dioxide, q) 4-piperidinyl-1-acetyl, r) 4-piperidinyl-1-dimethylcarboxamide, and s) 3-tetrahydrothiophenyl-1,1-dioxide; v) substituted oxopiperazine with the formula where R denotes -H; and vi) substituted piperidine with the formula where R denotes -CONH2, -OH, -CH2OH, -CH2CH2OH, 1-pyrrolidinyl, 1-piperidinyl, 1-(4-methylpiperazinyl) or 4-morfolinil. Moreover, the invention refers to the pharmaceutical composition based on the compound with the formula (I), to application of the formula (I) compound for production of a drug, to the production process of the formula (I) compound.

EFFECT: new derivatives of dihydroimidazole that may be used as anticancer drugs.

40 cl, 204 ex

FIELD: chemistry.

SUBSTANCE: present invention is related to new quinolone derivatives of general formula (I) where R1: C3-6cycloalkyl or lower alkylene C3-6cycloalkyl, R2: -H or halogen, R3: -H, halogen, -OR0 or -O-(lower alkylene)-phenyl, R0: are the same or different from each other, and each represents -H or lower alkyl, R4: lower alkyl, halogen(lower alkyl), lower alkyleneC3-6cycloalkyl, C3-7cycloalkyl or a heterocyclic group, where cycloalkyl and the heterocyclic group specified in R4 can be respectively substituted, R5: -NO2, -CN, -L-Ra, -C(O)R0, -O-Rb, -N(R6)2, lower alkylene-N(R6)(Rc), -N(R6)C(O)-Rd, lower alkylene-N(R6)C(O)-Rd, lower alkylene-N(R0)C(O)O-(lower alkyl), -N(R0)C(O)N(R0)-Re, lower alkylene-N(R0)C(O)N(R0)-Re, -N(R0)S(O)2N(R0)C(O)-Rd, -CH=NOH, C3-6cycloalkyl, (2,4-dioxo-1,3-thiazolidin-5-yliden)methyl or (4-oxo-2-tioxo-1,3-thiazolidin-5-yliden)methyl where cycloalkyl specified in R5 can be respectively substituted, R6: H, lower alkyl, lower alkylene-CO2R0 or lower alkylene-P(O)((OPp)2, where lower alkylene specified in R6 can be substituted, L: lower alkylene or lower alkenylene which can be respectively substituted, Ra: -OR0, -O-(lower alkylene)-phenyl, -O-(lower alkylene)-CO2R0, -CO2R0, -C(O)NHOH, -C(O)N(R6)2, -C(O)N(R0)-S(O)2-(lower alkyl), -C(O)N(R0)-S(O)2-phenyl, -C(O)N(R0)-S(O)2-(heterocyclic group), -NH2OH, -OC(O)R0, -OC(O)-(halogen(lower alkyl)), -P(O)(ORp)2, phenyl or the heterocyclic group where phenyl or the heterocyclic group specified in Ra can be substituted, Rp: R0, lower alkylene-OC(O)-(lower alkyl), lower alkylene-OC(O)-C3-6cycloalkyl, lower alkylene-OC(O)O-(lower alkyl), Rb: H, lower alkylene-Rba or lower alkenylene-Rba where lower alkylene or lower alkenylene specified in Rb can be substituted, Rba: -OR0, -CO2R0, -C(O)N(R0)2, -C(O)N(R0)-S(O)2-(lower alkyl), -C(O)N(R0)-S(O)2-[phenyl, -C(NH2)-NOH, -C(NH2)=NO-C(O)-(lower alkylene)-C(O)R0, -CO2-(lower alkylene)-phenyl, -P(O)(ORp)2, -C(O)R0, -C(O)-phenyl, C3-6cycloalkyl, phenyl or the heterocyclic group where phenyl and the heterocyclic group specified in Rba can be substituted, Rc: H, lower alkylene-OR0, lower alkylene-CO2R0, lower alkylene-P(O)((OPp)2, phenyl where lower alkylene and phenyl are specified in Rd can be substituted, Rd: C1-7-alkyl, lower alkenyl, halogen(lower alkyl), lower alkylene-Rda, lower alkylenylene-Rda, C3-6cycloalkyl, phenyl, naphthyl or the heterocyclic group, where lower alkylene, cycloalkyl, phenyl, naphthyl and the heterocyclic group specified in Rd can be substituted, Rda: -CN, -OR0, -O-(lower alkylene)-CO2R0, -O-naphthyl, -CO2R0, -CO2-(lower alkylene)-N(R0)2, -P(O)(ORp)2, -N(R6)2, -C(O)N(R0)-phenyl, -C(O)N(R0)-(lower alkylene which can be used by -CO2R0)-phenyl, -N(R0)C(O)-phenyl, -N(R0)C(O)-OR0, -N(R0)C(O)-O-(lower alkylene)-phenyl, -N(R0)S(O)2-phenyl, C3-6cycloalkyl, phenyl, naphthyl or the heterocyclic group, where phenyl, naphthyl and heterocyclic group specified in Ra can be substituted, Re: lower alkylene-CO2R0, phenyl, -S(O)2-phenyl or -S(O)2-(heterocyclic group), where phenyl and the heterocyclic group specified in Re can be substituted, X: CH, A: C(R7), R7: -H, or R4 and R7 together can form lower alkylene, where the substituted groups have the substituted specified in cl.1, and provided 7-(cyclohexylamino)-1-ethyl-6-fluor-4-oxo-1,4-dohydroquinoline-3-carbonitryl is excluded. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I) and application of formula (I) for preparing a thrombocyte aggregation inhibitor or a P2Y12 inhibitor.

EFFECT: there are produced new quinol-4-one derivatives showing effective biological properties.

11 cl, 83 tbl, 71 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to 5-nitrofuran derivatives of formula I: where R=piperidino, pyrrolidineo, diethylamino, morpholino.

EFFECT: presented preparation of new biologically active compounds which exhibit antimicrobial activity.

1 cl, 4 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general structural formula:

or to pharmaceutically acceptable salts, where Z denotes -O- or -CH2- or -CH2-CH2-; X1 denotes a covalent bond or -O-; Y1 denotes a covalent bond or C1-C10 alkylene, provided that Y1 is a covalent bond only when X1 denotes a covalent bond; R1 denotes a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which is a monovalent heteroatomatic monocyclic radical ring containing 1-2 heteroatoms, independently selected from nitrogen and sulphur, possibly substituted with 1-3 groups, independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-alkoxy; R2 denotes -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(NHR9) or -NHC(O)H, where R9 denotes a linear or branched C1-C5 alkyl or a linear or branched (C1-C5)alkoxyalkyl; R3 denotes H, C1-C5 alkyl, -NHC(O)R10 or OH, where R10 denotes C1-C3 alkyl, provided that when R3 denotes -OH, X1 is not O and R2-Y1-X1 is not -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9 or -NHC(O)H; -Q denotes

, where N and N are bonded by bonds denoted by a wavy line; R4 denotes H; R5 and R6 independently denote: a) H, (C1-C10)alkyl, (C4-C10)cycloalkylalkyl, hydroxylated (C4-C10)cycloalkylalkyl, halo(C4-C10)cycloalkylalkyl, (C1-C2)alkyl(C4-C10)cycloakylalkyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl, where the saturated heterocyclic ring is selected from 5-, 6- or 7-member heterocyclic rings which contain 1 heteroatom independently selected from N and O; or b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which is possibly with 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that both R5 and R6 are not H; G denotes NH2 or NHR7; R7 denotes (C1-C6)alkyl; or R5 and R7 together denote -CH2, -(CH2)2 or -(CH2)3, possibly substituted with 1-2 groups independently selected from (C1-C8)-alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy. The invention also relates to compounds selected from the group, pharmaceutical compositions, a method for antagonising one or more aspartate proteases, as well as methods of treating aspartate protease-mediated disorders.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

35 cl, 33 ex, 4 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a heterocyclic compound or salt thereof, having formula (1): where R2 is hydrogen or a lower alkyl group; A is a lower alkylene group or a lower alkenylene group and R1 is a cyclo(C3-C8)alkyl group, an aromatic group or a heterocyclic group selected from a group consisting of groups (I)-(IV), defined in the formula of invention. The invention also relates to a pharmaceutical composition, having activity as a partial agonist of dopamine D2 receptors and/or a serotonin 5-HT2A receptor antagonist and/or an adrenalin α1 receptor antagonist and/or a serotonin absorption inhibitor and/or serotonin reuptake inhibitor based on said compounds, a method of preparing a pharmaceutical composition, use of said compounds as a partial agonist of dopamine D2 receptors and/or a serotonin 5-HT2A receptor antagonist and/or an adrenalin α1 receptor antagonist and/or a serotonin absorption inhibitor and/or serotonin reuptake inhibitor, as well as a method of producing formula I compounds.

EFFECT: novel compounds are obtained and described, which have a wide range of curative effect on mental disorders, including central nervous system disorders, without side effects and with high degree of safety.

22 cl, 3110 ex, 314 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel substituted imidazole compounds of formula I where values of radicals are given in description, as well as to their based on them pharmaceutical compositions.

EFFECT: formula I compounds, as well as their salts, esters and compositions based on them possess ability to inhibit protein of kinesin spindle (KSP) and can be used for treatment of cancer diseases.

40 cl, 15 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula: I, where R1 is selected from group, consisting of ethyl, 2-fluorethyl and isopropyl; R2 is selected from group, consisting of hydrogen, C1-7-alkyl, hydroxy, C1-7-alkoxy, C3-7-cycloalkyl, halogen, -C(O)OR6, where R6 represents C1-7-alkyl, amino, phenyl, phenyl, substituted with 1-3 substituents, selected from group, consisting of halogen, halogen-C1-7-alkyl and halogen-C1-7-alkoxy, pyridyl, imidazolyl, triazolyl and pyrrolyl; R3 is selected from group, consisting of hydrogen, C1-7-alkoxy, amino, -O-benzyl and -o-tetrahydropyranyl; or R2 and R3 are bound to each other with formation of cycle together with carbon atoms to which they are bound, and R2 and R3 together represent -CH=CH-NH-; R4 is selected from group, consisting of hydrogen, halogen, pyridyl and pyrimidyl; R5 and R5' independently on each other are selected from hydrogen or methyl; A is selected from group, consisting of isphenyl; phenyl, substituted with 1-3 substituents, selected from group, consisting of C1-7-alkyl, C3-7-cycloalkyl, C1-7-alkylsulfonyl, -O-C1-7-alkylsulfonyl, hydroxy, C1-7-alkoxy, hydroxy-C1-7-alkyl, hydroxy-C2-7-alkoxy, dihydroxy-C3-7-alkoxy, C1-7-alkylamino, di-C1-7-alkylamino, amino-C2-7-alkoxy, amino-C1-7-alkyl, -C(O)NR10R11, -O-C1-7-alkylene-C(O)NR10R11, -C(O)OR10, -C1-7-alkylene-C(O)OR10, -O-C1-7-alkylene-C(O)OR10, halogen, halogen-C1-7-alkoxy, cyano- C1-7-alkoxy, fluorphenyl, pyridyl, tetrazolyl and tetrazolyl- C1-7-alkoxy; 1,3-benzodioxolyl; naphtyl; pyrimidinyl; pyridyl, substituted with one or two substituents, selected from group, consisting of C1-7-alkyl, C1-7-alkoxy, amino, C1-7-alkylamino, di-C1-7-alkylamino, C3-7-cycloalkylamino, halogen, cyano, morpholinyl, imidazolyl and -NH-C(O)-R9, where R9 represents C1-7-alkyl or C3-7-cycloalkyl, and indolyl; R10 and R11 independently on each other represent hydrogen or C1-7-alkyl; and to their pharmaceutically accdeptable salts. Invention also relates to pharmaceutical compositions.

EFFECT: obtaining novel biologically active compounds, which are antagonists of somatostatin receptor subtype 5 (SSTR5).

26 cl, 266 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula I or its pharmaceutically acceptable salt , where R, R9, Z, X, Q and Y are defined in the formula of invention. The compounds are chemokine receptor 2 and chemokine receptor 5 antagonists and can be used as a medicinal agent for preventing, relieving or treating autoimmune or inflammatory diseases or conditions.

EFFECT: obtaining a formula (I) compound, a pharmaceutical composition based on the formula (I) compound, use of the compound in paragraph 1 to prepare a medicinal agent for treating an autoimmune or inflammatory disease or condition, as well as use of the compound in paragraph 1 to prepare a medicinal agent for treating HIV infection or AIDS.

11 cl, 181 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to new compounds - pluraflavines of the formula (I): wherein R1 represents sugar group of the formula: ; R2 represents -COOH or -CH2-O-(R7)m wherein R7 represents sugar group of the formula: ; R3 is taken among the groups: and , and to all its stereochemical forms and mixtures of indicated forms in any ratio, and to their physiologically acceptable salts; R5 means hydrogen atom; R4 and R6 represent in common group -X2 with a double bond wherein X2 means oxygen atom (O); R8 and R10 represent in common group -X2 with a double bond wherein X2 means oxygen atom (O), and m = n = 1, and to all its stereochemical forms and mixtures of indicated forms in any ratio and to its physiologically acceptable salts. Invention relates to a method for preparing these compounds from culture of microorganism actinomycetes HAG 003959, DSM 12931 by fermentation, to the strain Actinomycetales HAG 003959, DSM 12931 used for preparing compounds of the formula (I) and to pharmaceutical composition inhibiting transcriptase activity and eliciting cytotoxic effect based on above said compounds. Compounds of the formula (I) are used as medicinal agents, for example, as antitumor agents.

EFFECT: improved method for preparing, valuable medicinal properties of compounds and composition.

19 cl, 3 tbl, 12 ex

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