Azaheterocycles, combinatory library, focused library, pharmaceutical composition and method for preparing (variants)

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel azaheterocycles of the general formula (I): possessing inhibitory effect on activity of tyrosine kinase and can be used in treatment of different diseases mediated by these receptors. In compound of the general formula (1) W represents azaheterocycle comprising 6-13 atoms that can be optionally annelated with at least one (C5-C7)-carbocycle and/or possibly annelated with heterocycle comprising 4-10 atoms in ring and comprising at least one heteroatom chosen from oxygen (O), sulfur (S) or nitrogen (N) atom; Ra1 represents a substitute of amino group but not hydrogen atom, such as substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-10-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; Rb represents carbamoyl group -C(O)NHRa wherein Ra represents a substitute of amino group but not hydrogen atom, such as possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyc comprising at least one heteroatom chosen from O, S or N; Rc represents a substitute of cyclic system, such as possibly substituted (C1-C6)-alkyl, possibly substituted aryl and possibly substituted 5-6-membered heterocyclyl comprising at least one heteroatom chosen from O, S or N; or Rb and Rc form in common aminocyanomethylene group [(=C(NH2)CN], or their pharmaceutically acceptable salts. Also, invention relates to methods for synthesis of these compounds (variants), a pharmaceutical composition, combinatory and focused libraries.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved methods for synthesis and preparing.

35 cl, 16 sch, 13 tbl, 43 ex

 

The text descriptions are given in facsimile form.

1. Azaheterocycle General formula 1

where W represents azaheterocycle, including 6-13 atoms, optional annelirovannymi at least one C5-C7carbocycles and/or possibly the fused heterocycle with 4 to 10 atoms in the ring, and including at least one of the heteroatoms selected from the group O, S or N;

R1ais a Deputy amino group, excluding hydrogen, such as, possibly substituted C1-C6alkyl, possibly substituted aryl or possibly substituted 5-10-membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N; Rbare karbamoilnuyu group-C(O)otherain which Rais a Deputy amino group, excluding hydrogen, such as a possibly substituted alkyl, possibly substituted aryl, possibly substituted 5-10-membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N; Rcare Deputy cyclic systems, such as possibly substituted C1-C6alkyl, perhaps C is displaced aryl or possibly substituted 5-6-membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N, or Rband Rctogether form an amino-cyano-methylene group [(=C(NH2)CN]; or their pharmaceutically acceptable salts, including templates T-1.1 T-1.41; T-2.1-T; T-3.1 T-3.2:

in which the dotted line with its accompanying solid line (represents a single or double bond, and excluding azaheterocycle, including fragments In(1-29), azaheterocycle C1(1-6) and C2(1-17)

2. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.1-1.5

where the dotted line with its accompanying solid line () is one the RNA or double bond; R1a, Rband Rchave the above meaning; R2ais a Deputy amino group, such as a hydrogen atom, possibly substituted C1-C6alkyl, each of R1dand R2d, R3dand R4dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl, or

R1dand R2afor compounds 1.1, 1.2 and 1.3 and R2dand R2afor connections 1.4 and 1.5 can form together with the atoms to which they are linked, possibly substituted 4-10-membered azaheterocycles may contain additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly condensed with a benzene ring or another 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and

R3dand R2dfor compounds 1.3, R1dand R2dfor connections 1.4 and 1.5, and R4dand R3dfor connections 1.5 together with the atoms to which they are linked, may form a possibly substituted aliphatic cycle, containing 4-12 carbon atoms, POS is but substituted mono - or condensed barometrically cycle or possibly substituted 5-6-membered heterocycle, in which heteroatoms selected from nitrogen, oxygen or sulfur, and which may be condensed with another possibly substituted 5-6-membered heterocycle containing as heteroatoms nitrogen, oxygen or sulfur, or

Rcand R2dfor compounds 1.2, or Rcand R3dfor connections 1.3 and 1.4, or Rcand R4dfor connections 1.5 together with the atoms to which they are linked, may form a possibly substituted aliphatic cycle, containing 4-12 carbon atoms or a possibly substituted 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and which may be condensed with another possibly substituted 5-6-membered heterocycle containing as heteroatoms nitrogen, oxygen or sulfur.

3. Compounds according to claim 1, which represents a substituted benzodiazepines General formula 1.6

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rband Rchave the above significance, each of R1d, R2dand R3dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly C is displaced C 1-C6of alkyl, possibly substituted aryl, or

R3dand R2dtogether with the atoms to which they are linked, may form a possibly substituted mono - or condensed barometrically cycle, possibly substituted 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and which may be condensed with another possibly substituted 5-6-membered heterocycle containing as heteroatoms nitrogen, oxygen or sulfur, or possibly substituted aliphatic cycle, containing 4-12 carbon atoms, and

R1dand R2amay form together with the atoms to which they are linked, possibly substituted 4-6-membered azaheterocycles may contain additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly condensed with a substituted benzene ring or another possibly substituted 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, oxygen or sulfur.

4. Compounds according to claim 3, represents 3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]benzodiazepines, General formula 1.6.1

where R1a, R2a, Rb, Rcand R1dhave the above for the 1.6 value; Rndp is ecstasy a one or two Vice-cyclic system, selected from hydrogen, possibly substituted C1-C6-alkyl, nitro, halogen, amino, C1-C6acylamino, arylsulfonyl-amino, arylenecarborane, possibly substituted 5-6-membered azaheterocycles.

5. Compounds according to claim 3 or 4, a 3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]benzodiazepines, including template General formula 1.6.1.1-1.6.1.16

where Rband Rchave the above value.

6. Compounds according to claim 1, which represents a 7-oxazepan General formula 1.7

where the dotted line with its accompanying solid line (represents a single or double bond; R1a, Rband Rchave the above meaning; R1dand R2#x0200A; dtogether with the atoms to which they are linked, and R3dand R4dtogether with the atoms to which they are linked, form, respectively, possibly substituted aromatic cycle or possibly substituted 5-6-membered azaheterocycles may contain additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly condensed with a benzene ring or another 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, oxygen, or sulfur, or a possibly substituted aliphatic cycle, containing 4-12 carbon atoms.

7. Compounds according to claim 6, representing kannelirovannye 7-oxazepine, including template General formula 1.7.1-1.7.74

where Rband Rchave the above value.

8. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.8-1.15

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, Rband Rchave the above meaning; R2ais a Deputy amino group, such as a hydrogen atom, possibly substituted C1-C6alkyl, each of R1d, R2d, R3d, R4dand R5dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl, or

R1dand R2afor connections, 1.8, 1.9, R2aand R2dfor connections 1.10, 1.11, R2aand R3dfor connections 1.12 and 1.13, R2aand R4dfor connections 1.14, 1.15 can form together with the atoms to which they are linked, possibly substituted 4-6-membered azaheterocycles may contain additional heteroatoms selected from nitrogen, oxygen or sulfur, and possibly condensed with a substituted benzene ring or another possibly substituted 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, oxygen or sulfur, and

R1dand R2dfor connections 1.9, 1.12, 1.13, 1.14, 1.15, R2dand R3dfor connections 1.11, 1.14, 1.15, R4dand R3dfor connections 1.13, R4dand R5dfor connections 1.15 together with the atoms to which they are linked, may form a possibly substituted aliphatic cycle comprising 4 to 12 carbon atoms, possibly substituted mono - or condensed barometrically cycle or possibly substituted 5-6-membered heterocycle, in which the heteroatoms are selected from nitrogen, sour what kind or sulfur, and which may be condensed with another possibly substituted 5-6-membered heterocycle containing as heteroatoms nitrogen, oxygen or sulfur.

9. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.16-1.18

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rband Rchave the above meaning; R3ais a Deputy amino group selected from the group of hydrogen, possibly substituted alkyl, possibly substituted cycloalkyl, possibly substituted aryl; R1d, R2d, R3dand R4dindependently from each other represent a cyclic system substituents selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl, or compounds 1.16 R2dand R3atogether with the atoms to which they are linked, may form a through R2dand R3apossibly substituted azaheterocycle; or for connections 1.17 independent R3dand R3a together with the atoms to which they are linked, may form a through R3dand R3apossibly substituted 4-6-membered azaheterocycles, a R1dand R2dtogether with the atoms to which they are linked, may form a through R1dand R2dpossibly substituted aromatic cycle, 5-6-membered ring possibly substituted heterocycle comprising at least one heteroatom selected from the group O, S or N, or an aliphatic cycle, comprising from 4 to 12 carbon atoms; or for connections 1.18 independent R1dand R2dtogether with the atoms to which they are linked, may form a through R1dand R2dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, and R3aand R3dtogether with the atoms to which they are linked, may form a through R3aand R3dpossibly substituted 4-6-membered azaheterocycles, a R3dand R4dtogether with the atoms to which they are linked, may form a through R3dand R4dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms.

10. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.19 or 1.20

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rband Rchave the above meaning; R1d, R2d, R3dand R4dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6the alkyl or compounds 1.19 independent R1dand R2dtogether with the atoms to which they are linked, may form a through R1dand R2dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 1 carbon atoms, a R2aand R3dtogether with the atoms to which they are linked, may form a through R2aand R3dpossibly substituted 4-6-membered azaheterocycles; or for connections 1.20 independent R1dand R2dtogether with the atoms to which they are linked, may form a through R1dand R2dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, R2aand R3dtogether with the atoms to which they are linked, may form a through R2aand R3dpossibly substituted 4-6-membered azaheterocycles, and R3dand R4dtogether with the atoms to which they are linked, may form a through R3dand R4dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms.

11. Connection of claim 10, which represents a substituted azaheterocycle the General formula 1.19.1 or 1.20.1

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rb, Rc, R3dand R4dhave the above for 1.19 and 1.20 value, Rndrepresents one or two Vice-cyclic system selected from hydrogen, possibly substituted C1-C4-alkyl.

12. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.21 or 1.22

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rband Rchave the above meaning; R1d, R2d, R3dand R4dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6-alkyl, or for connections 1.21 independent R1dand R2dtogether with the atom to which they are bound, may form a through R1Ȁ dand R2dpossibly substituted C3-C6-cycloalkyl, R2aand R2dtogether with the atoms to which they are linked, may form a through R2aand R2dpossibly substituted 5-6-membered azaheterocycles may contain additional heteroatoms selected from nitrogen, oxygen, or sulfur, a R3dand R4dtogether with the atoms to which they are linked, may form a through R3dand R4dpossibly substituted 5-6-membered azaheterocycles; or for connections 1.22 independent R1dand R2dtogether with the atoms, with kotorii they are linked, may form a through R1dand R2dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms; R2aand R2dtogether with the atoms to which they are linked, may form a through R2aand R2dpossibly substituted 5-6-membered azaheterocycles may contain an additional heteroatom selected from nitrogen, oxygen or sulfur, and R3Ȁ dand R4dtogether with the atoms to which they are linked, may form a through R3dand R4dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms.

13. Connection 12, which represents a substituted azaheterocycle General formula 1.21.1 or 1.22.1

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rb, Rc, R1dand R2dhave the above for 1.21 and 1.22 is, Rndrepresents one or two Vice-cyclic system selected from hydrogen or a possibly substituted C1-C6-alkyl.

14. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.23-1.33

where a is an atom, O, S or NR2a; dotted line with its accompanying solid line (represents a single or double bond; R1a, Rband Rchave the above meaning; R2ais a Deputy amino group, such as a hydrogen atom, possibly substituted C1-C6alkyl, each of R1d, R2d, R3d, R4d, R5dand R6dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl, or compounds 1.23 and 1.27 R1dand R2dtogether with the atom to which they are bound, may form a through R1dand R2dpossibly substituted C5-C6cycloalkyl; for connections 1.23, 1.25, 1.27, 1.28, 1.30, 1.31, 1.33 R3dand R4dtogether with the atoms to which they are linked, may form a through R3dand R4dpossibly substituted aromatics the third cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, and compounds 1.23, 1.24, 1.25, 1.26 Rcand R4dtogether with the atoms to which they are linked, may form a through Rcand R4dpossibly substituted cycloalkyl or possibly substituted 5-6-membered heterocycle; or for connections 1.24, 1.25, 1.26, 1.28, 1.29, 1.30, 1.31, 1.32, 1.33 independent R1dand R2dtogether with the atoms to which they are linked, may form a through R1dand R2dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms; for connections 1.24 R3dand R4dtogether with the atom to which they are bound, may form a through R3dand R4dpossibly substituted C5-C6cycloalkyl, a Rcand R4dtogether with the atoms to which they are linked, may form a through Rcand R4dpossibly substituted C5-C6cycloalkyl; or D. the I compounds 1.26 R 2dand R3dtogether with the atoms to which they are linked, can form, respectively, by R2dand R3dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms; for connections 1.27, 1.29, 1.30, 1.31 and 1.32 R4dand R5dtogether with the atoms to which they are linked, may form a through R4dand R5dpossibly substituted cycloalkyl; for connections 1.26,1.27, 1.29, 1.30 Rcand R5dtogether with the atoms to which they are linked, may form a through Rcand R5dpossibly substituted C5-C6cycloalkyl; for connections 1.28 R5dand R6dtogether with the atom to which they are bound, may form a through R5dand R6dpossibly substituted C5-C6cycloalkyl, a Rcand R6dtogether with the atoms to which they are linked, may form a through Rcand R6dpossibly substituted C5-C6cycloalkyl; for connections 1.31, 1.32, 1.33 R5dand R6d together with the atoms to which they are linked, may form a through R5dand R6dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, a Rcand R6dtogether with the atoms to which they are linked, may form a through Rcand R6dpossibly substituted C5-C6cycloalkyl or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N; or for connections 1.32, 1.33 R2dand R3dtogether with the atoms, with kotorii they are linked, may form a through R2dand R3dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms.

15. Compounds according to claim 1, which represents a substituted azaheterocycle General formula 1.37-1.40

where the dotted line with its accompanying solid line (represents a single or double bond, R1a, R2a, Rband Rchave the above meaning; R4ais a Deputy amino group selected from a possibly substituted C1-C6of alkyl; each of R1d, R2d, R4dand R5dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl, or compounds 1.37 R1dand R2dtogether with the atom to which they are bound, may form a through R1dand R2dpossibly substituted C5-C6cycloalkyl, R2aand R4atogether with the atoms to which they are linked, may form a through R2aand R4apossibly substituted 5-6-membered azaheterocycles, a Rcand R4dtogether with the atoms to which they are linked, may form a through Rcand R4dpossibly substituted C5-C6cycloalkyl or possibly substituted 5-6-membered heterocycle comprising, according to what ina least one of the heteroatoms selected from the group O, S or N; or for connections 1.38 independent R1dand R2dtogether with the atom to which they are bound, may form a through R1dand R2dpossibly substituted C5-C6cycloalkyl or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, R2aand R4atogether with the atom to which they are bound, may form a through R2aand R4apossibly substituted azaheterocycle, a Rcand R4dtogether with the atoms to which they are linked, may form a through Rcand R4dpossibly substituted C5-6cycloalkyl or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N; or for connections 1.39 independent R1dand R2dtogether with the atom to which they are bound, may form a through R1dand R2dpossibly substituted C5-6cycloalkyl or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, R2aand R4atogether with the ohms, to which they are linked, may form a through R2aand R4apossibly substituted 5-6-membered azaheterocycles, independent R4dand R5dtogether with the atoms to which they are linked, may form a through R4dand R5dpossibly substituted aromatic cycle may annelirovannymi possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, a Rcand R5dtogether with the atoms to which they are linked, may form a through Rcand R5dpossibly substituted C5-6cycloalkyl or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N; or for connections 1.40 independent R1dand R2dtogether with the atom to which they are bound, may form a through R1dand R2dpossibly substituted cycloalkyl or possibly substituted heterocycle, R2aand R4atogether with the atom to which they are bound, may form a through R2aand R4apossibly substituted 5-6-clenn the th azaheterocycle, R4dand R5dtogether with the atoms to which they are linked, may form a through R4dand R5dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, a Rcand R5dtogether with the atoms to which they are linked, may form a through Rcand R5dpossibly substituted cycloalkyl or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N.

16. Azaheterocycle General formula 2.1-2.4 and their pharmaceutically acceptable acid additive salt

where R1ais a Deputy amino group, preferably a possibly substituted C1-C6alkyl, possibly substituted aryl or possibly substituted 5-6-membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N; R2aand R3aindependently from each other represent a Deputy shall stitely amino group, selected from the group of hydrogen, possibly substituted alkyl, possibly substituted aryl; R1d, R2d, R3d, R4d, R5d, R6d, R7dand R8dindependently from each other represent a Deputy cyclic system selected from hydrogen, possibly substituted C1-C6of alkyl, possibly substituted aryl or possibly substituted 5-6-membered heterocyclyl, including at least one of the heteroatoms selected from the group O, S or N, or perhaps replaced With3-6cycloalkyl; or R1dand R2dtogether with the carbon atom to which they are bound, may form a through R1dand R2dpossibly substituted C3-6cycloalkyl; or for compounds 2.1 and 2.2 R3d, R4d, R5d, R6dtogether with the atoms to which they are linked, may form a through R4dand R5dpossibly substituted aromatic cycle or possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms; or R2 atogether with the atom to which it is linked, and R3dand R4dtogether with the atoms to which they are linked, form a through R2aand R3dand R4dpossibly substituted 5-6-membered azaheterocycles; or R3atogether with the atom to which it is linked, and R5dand R6dtogether with the atoms to which they are linked, form a through R3aand R5dand R6dpossibly substituted 5-6-membered azaheterocycles; or R2atogether with the atom to which it is linked, and R3d, R4d, R5dand R6dtogether with the atoms to which they are linked, form a through R2a, R4dand R5dpossibly substituted 5-6-membered azaheterocycles; or R3atogether with the atom to which it is linked, and R3d, R4d, R5dand R6dtogether with the atoms to which they are linked, form a through R3a, R4dor R5dand R6dpossibly substituted 5-6-membered azaheterocycles; or for connections 2.3 and 2.4, R3d, R4d, R5dand R6dtogether with the atoms to which they are linked, form a through R4dand R5dpossibly substituted aromatic cycle, possibly substituted 5-6-membered heterocycle comprising at least one heteroatom selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms; or R5d, R6d, R7dand R8dtogether with the atoms to which they are linked, form a through R7dand R5dpossibly substituted aromatic cycle, possibly substituted 5-6-membered azaheterocycles, including at least one of the heteroatoms selected from the group O, S or N, or a possibly substituted aliphatic cycle, comprising from 4 to 12 carbon atoms, excluding piperazine E

17. Azaheterocycle General formula 3.1 or 3.2

where connections 3.1 R1aand R2aindependently from each other represent a Deputy amino group selected from a possibly substituted C1-6of alkyl, possibly substituted cycloalkyl, possibly substituted aryl; R1drepresents aryl; R2dnot only is em a hydrogen atom or a C 1-C6alkyl, or R1dand R2dtogether with the atom to which they are bound, form a through R1dand R2dcycloalkyl or 5-6-membered heterocyclyl; R3dand R4dindependently from each other represent a Deputy cyclic system selected from C1-C6the alkyl, or R3dand R4dtogether with the carbon atom to which they are bound, form a through R3dand R4dcycloalkyl or possibly substituted 5-6-membered azaheterocycles; for connections 3.2 R1ais a Deputy amino group; R1drepresents aryl or heterocyclyl; R2drepresents a hydrogen atom or a C1-C6alkyl, or R1dand R2dtogether with the atom to which they are bound, form a through R1dand R2dC5-C6cycloalkyl or 5-6-membered heterocycle; R2atogether with the atom to which it is linked, and R3dtogether with the atom to which it is linked, form a through R2aand R3d5-6-membered azaheterocycles, excluding piperazinone General formula D

where R1a=N, CH3; R2a= optionally substituted alkyl; R1daryl or optionally substituted alkyl; R2dand R3d= optionally substituted alkyl, or R2dand R3dtogether with the carbon atom to which they are connected, form a through R2dand R3dcyclopropane.

18. Connection 17, which represents azaheterocycle, including the fragment of the formula 3.1.1-3.1.7

19. The method of producing azaheterocycles General formula 1.1-1.5 according to claim 2 interaction bifunctional reagent of General formula 4.5(1-5)selected from the group below, or optionally N-protected amino acids of General formula 4.1(1-3)selected from the group below, and ether oxo-carboxylic acids of General formula 4.2(1-3)selected from the group below, with isonitriles General formula2and the primary amine of General formula3in the environment of an organic solvent, however, in the case of preparing compounds in which Rband Rctogether represent sabinecretella =C(other 3a)CN, the reaction is carried out in the presence of an acid catalyst

where R' represents hydrogen or (CH3)3SOS(Oh);

R" represents alkyl or aryl;

R1a, R2a, R3a, Rc, R1d, R2d, R3dand R4dhave the meanings specified above for compounds of General formula 1.1-1.5.

20. The method of producing azaheterocycles General formula 1.6 according to claim 3 interaction in the environment of organic solvent isonitrile General formula2the primary amine of General formula3and bifunctional reagent of General formula 4.7, or optionally N-protected amino acids of General formula 4.1 and halogenocarboxylic compounds of General formula 4.6, followed by cyclization of the resulting adducts, and to obtain the compounds of General formula 1.6, in which Rband Rctogether represent aminocinnamate is eh =C(other 3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R2a, R3a, Rc, R1d, R2dand R3dhave the meanings specified above for azaheterocycles General formula 1.6; R' represents hydrogen or (CH3)3SOS(ON).

21. The method of obtaining Azarov General formula 1.7 6 interaction bifunctional reagent of General formula 4.8, isonitrile General formula2and the primary amine of General formula3in the environment of an organic solvent, whereby to obtain compounds of General formula 1.7, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R3a, Rc, R1d, R2d, R3dand R4dhave the meanings specified above for azaheterocycles General formula 1.7.

22. The method of obtaining and what heterocycles General formula 1.8-1.15 of claim 8 interaction of isonitrile General formula B 2the primary amine of General formula3in the environment of organic solvent and monoether dicarboxylic acid of General formula 4.9(1-4) and optionally protected amino-carbonyl compounds of General formula 4.10(1-3) followed by cyclization of the resulting adducts or bifunctional reagent of General formula 4.11(1-8), and to obtain the compounds of General formula 1.8-1.15, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R2a, R3a, Rc, R1d, R2d, R3d, R4dand R5dhave the meanings specified above for azaheterocycles General formula 1.8-1.15.

23. Ways is getting azaheterocycles General formula 1.16-1.18 according to claim 9 interaction in the environment of organic solvent isonitrile General formula 2the primary amine of General formula3and bifunctional reagent of General formula 4.12(1-3), and to obtain the compounds of General formula 1.16-1.18, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R2a, R3a, Rc, R1d, R2d, R3dand R4dhave the meanings specified above for azaheterocycles General formula 1.16-1.18.

24. The method of producing azaheterocycles General formula 1.19, 1.20 of claim 10 interaction in the environment of organic solvent isonitrile General formula2the primary amine of General formula3and bifunctional reagent of General formula 4.13(1,2), and to obtain the compounds of General formula 1.19, 1.20, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

p num="137"> where R1a, R2a, R3a, Rc, R1d, R2d, R3dand R4dhave the meanings specified above for azaheterocycles General formula 1.19,1.20.

25. The method of producing azaheterocycles General formula 1.21, 1.22 on para.12 interaction in the environment of organic solvent isonitrile General formula2the primary amine of General formula3and bifunctional reagent of General formula 4.14(1,2), and to obtain the compounds of General formula 1.21, 1.22, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R2a, R3a, Rc, R1d, R2d, R3dand R4dhave the meanings specified above for azaheterocycles General formula 1.21, 1.22.

26. The method of producing azaheterocycles General formula 1.23-1.33 on 14 interaction of isonitrile General formula B2the primary amine of General formula3substituted acid of General formula 4.15(1-4) and the halogen-carbonyl connected to the I General formula 4.16(1-4) in an organic solvent with subsequent cyclization of the resulting adducts, moreover, to obtain the compounds of General formula 1.23-1.33, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R3a, Rc, R1d, R2d, R3d, R4d, R5d, R6dand a have the meanings specified above for azaheterocycles General formula 1.23-1.33.

27. The method of producing azaheterocycles General formula 1.23-1.33 on 14 interaction of isonitrile General formula2the primary amine of General formula3corresponding halogen-substituted acids of General formula 4.17(1-4) and the appropriate substituted carbonyl compounds of General formula 4.18(1-4) in an organic solvent with subsequent cyclization of the resulting adducts, and to obtain the compounds of General formula 1.23-1.33, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in prisutstvie the acid catalyst

where R1a, R3a, Rc, R1d, R2d, R3d, R4d, R5d, R6dand a have the meanings specified above for azaheterocycles General formula 1.23-1.33.

So get azaheterocycles General formula 1.23-1.33 on 14 interaction of isonitrile General formula2the primary amine of General formula3and the corresponding bifunctional reagent of General formula 4.19.1-4.19.11 in the environment of an organic solvent, whereby to obtain compounds of General formula 1.23-1.33, in which Rband Rctogether they are aminocinnamate C(other3a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R3a, Rc, R1d, R2d, R3d, R4d, R5d, R6dand a have the meanings specified above for azaheterocycles General formula 1.23-1.33.

29. The method of producing azaheterocycles General formula 1.37, 1.39 on clause 15 of the interaction of isonitrile General formula2the primary amine of General formula3, (2,3-disubstituted-touraid)-acetic acid of General formula 4.20 and halogen-carbonyl compounds of General formula 4.21.1 4.21.2 or in the environment of an organic solvent with subsequent cyclization of the resulting adducts, or a bifunctional reagent of General formula 4.22.1 or 4.22.2 in the environment of an organic solvent, whereby to obtain compounds of General formula 1.37, 1.39, in which Rband Rctogether they are aminocinnamate C(other4a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R2a, R3a, R4a, Rc, R1 d, R2d, R3d, R4dand R5dhave the meanings specified above for azaheterocycles General formula 1.37, 1.39.

30. The method of producing azaheterocycles General formula 1.38, 1.40 on clause 15 of the interaction of isonitrile General formula2the primary amine of General formula3and halogen-carbonyl compounds of General formula 4.21.1 4.21.2 or and (3,3-disubstituted-touraid)-acetic acid of General formula 4.23 in the environment of an organic solvent with subsequent cyclization of the resulting adducts or bifunctional reagent of General formula 4.24.1 or 4.24.2, and to obtain the compounds of General formula 1.38, 1.40, in which Rband Rctogether they are aminocinnamate C(other4a)CN, the reaction is carried out in the presence of an acid catalyst

where R1a, R2a, R3a, R4a, Rc, R1d, R2d, R3d, R4dand R5dhave the meanings specified above for azaheterocycles General formula 1.38, 1.40.

31. The method of obtaining azaheterocycle what s the General formula 2.1-2.4 P16 interaction of carbonyl compounds of General formula 4.26, isonitrile General formula2and bifunctional reagent of General formula 4.27.1 or 4.27.2 in the medium of organic solvent

where R1a, R2a, R3a, R1d, R2d, R3d, R4d, R5d, R6d, R7dand R8dhave the meanings specified above for azaheterocycles General formula 2.1-2.4.

32. The method of producing azaheterocycles General formula 3.1, 3.2 on 17 interaction in the environment of organic solvent isonitrile General formula B2the primary amine of General formula3, carbonyl compounds of General formula 4.26 and optionally N-protected amino acids of General formula 4.28

where R1a, R2a, R3a, R1d, R2d, R3dand R4dhave the meanings specified above for azaheterocycles General formula 3.1, 3.2; R represents a hydrogen atom or (CH3 )3SOS(ON).

33. A combinatorial library to identify compounds leaders, consisting of azaheterocyclic compounds of General formula 1 according to claim 1, and/or azaheterocyclic compounds of the General formula 2.1, 2.2, 2.3 and 2.4 in clause 16, and/or azaheterocyclic compounds of the General formula 3.1 and 3.2 by 17.

34. Focused library to identify compounds leaders, containing at least one of azaheterocyclic compound of General formula 1 according to claim 1, and/or azaheterocyclic compound of General formula 2.1, 2.2, 2.3 and 2.4 in clause 16, and/or azaheterocyclic compound of General formula 3.1 and 3.2 by 17.

35. Pharmaceutical composition having anti-cancer activity and is intended to obtain drugs for treating and preventing various diseases in animals and humans in the form of tablets, capsules, or injections, placed in pharmaceutically acceptable packing, containing as active substance pharmaceutically effective amount of at least one of azaheterocyclic compounds of General formula 1 according to claim 1, and/or azaheterocyclic compounds of General formula 2.1, 2.2, 2.3 and 2.4 in clause 16, and/or azaheterocyclic compounds of General formula 3.1 and 3.2 to 17, or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compounds of the formula (I): and their salts, to methods for their preparing, compositions containing thereof and their using in medicine, in particular, for prophylaxis or treatment of clinical state wherein a selective agonist of β2-adrenoceptors is prescribed.

EFFECT: valuable medicinal properties of compound and compositions.

32 cl, 4 dwg, 82 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to new compounds of formula I , or stereoisomers, or pharmaceutically acceptable salts thereof, wherein Q is SO2; n = 2 or 3; each R1 and R2 is independently H, halogen, OR22 or C1-C6-alkyl; each R3 and R4 is H; each R5 and R6 is independently H or C1-C6-alkyl optionally substituted with phenyl or R5 and R6 together with together with atom to which they are attached may form 5-7-membered ring optionally containing N as the second heteroatom optionally substituted with COOH or C1-C6-alkyl; R7 is H; R7 is optionally substituted 8013-membered bicyclic or tricyclic ring system, containing N in bridge bond and optionally 1, 2 additional heteroatoms selected from N, S wherein substituent represent 1 or 2 halogen atoms; R22 is H or C1-C6-phenyl optionally substituted with C1-C6-alkyl. Compounds of present invention specifically bond to 5-HT6 receptor and are useful in pharmaceutical compositions.

EFFECT: compounds with specific bonding to 5-HT6 receptor.

10 cl, 3 tbl, 45 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I and pharmaceutically acceptable salt thereof, wherein R1, R3, R4, R5, and R10 are independently H, halogen, C1-C4-alkyl, etc.; R2 is H, halogen, NO2, etc.; R6 is H, C1-C6-alkyl, C1-C6-alkoxy-substituted C1-C4-alkyl, etc.; R7 is H, C1-C4-alkyl or C2-C4-alkenyl, optionally substituted with halogen; R8 and R9 are H, R11 and R12; meanings of the rest substituents are as define in specification.

EFFECT: new compounds with value biological properties and useful as drug having activity in relates to progesterone receptor.

15 cl, 3 tbl, 80 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to bicyclic 1,4-piridotiazine-1,1-dioxides of general formula I wherein R1 is chlorine or fluorine; R2 is linear or branched alkyl, cycloalkyl, optionally reduced aryl or heteroaryl, etc. Method for production of said compounds includes reaction of acyclic sulfones with primary alcohols, preferably in presence of inorganic or organic such as carbonates or alkali metal hydroxides tertiary organic amines or base mixtures, preferably in aprotic bipolar media without solvents, or mixture thereof with water.

EFFECT: safe method for production of new compounds useful as drugs.

2 cl, 2 ex

FIELD: medicine.

SUBSTANCE: compound is represented by structural formula

or its pharmaceutically permissible salts, where R1 is the hydrogen atom (1), C1-8acyl(2), hydroxyl (3), halogen atom (5), C2-8acyl (3), C1-8-alcocsy (4), substituted with phenyl or C2-8acyl, substituted with NR2R3; R2R3 independently represent hydrogen atom (1) or C1-8acyl(2), X and Y each independently representing C (1), CH (2) or N (3). is (1) single or (2) double bond. is 5-7-member carbocyclic group or 5-7-member partially or fully saturated heterocyclic group defined in claim 1 of invention. A is one of A1 to A5 groups defined by claim 1 of the invention. The compounds show inhibiting properties relative to poly(ADP-ribose)polymerase are usable as prophylactic and/or curative drugs for treating ischemic diseases (in brain, spinal cord, heart, digestive tract, skeletal muscle, eye retina, e.t.c.), inflammatory diseases (intestinal inflammation, disseminated sclerosis, arthritis, e.t.c.), neurodegenerative disorders (extrapyramidal disorder, Alzheimer disease, muscle dystrophy, cerebrospinal canal stenosis in lumbar segment of the vertebral column, e.t.c.), diabetes, stroke, cerebral injury, hepatic insufficiency, hyperalgesia, e.t.c. The compounds are also of use in struggling against retroviruses (HIV and others), as sensitizing agents for treating cancer cases and immunodepressant agents.

EFFECT: enhanced effectiveness of treatment.

19 cl, 90 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel lactam compounds of the formula (I) or their pharmaceutically acceptable salts wherein A means phenyl, thienyl, pyridyl, pyrimidinyl, pyrazinyl; R2, R3 and R4 can be similar or different and mean independently of one another hydrogen atom (H), halogen atom, -OH, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -NH2, -NO2, -CF3, phenyl that can comprise substitute(s), benzyloxy-group that can comprise substitute(s), pnehylvinyl, and one among R2, R3 and R4 means -CF3-O- and others mean H; B means phenyl that can comprises substitute(s), monocyclic aliphatic (C3-C8)-ring, dihydropyrane ring; -X- and -Y- xan be similar or different and they mean independently -O-, -NH-, -NR5-, -S-; Z means -CH2-, -NH-; W means -NR1-, -CR8R9- wherein R1 means H; R8 and R9 are similar or different and mean H; wherein R5 represents a linear alkyl group that can comprise substitute(s), (C1-C8)-linear or branched alkoxycarbonyl group, acyl group chosen from formyl group, acyl group comprising (C1-C6)-alkyl, (C1-C6)-alkenyl or (C1-C6)-alkynyl group that can comprise substitute(s), carbamoyl group comprising (C1-C6)-alkyl group at nitrogen atom that can comprise substitutes, sulfonyl group comprising (C1-C6)-alkyl group at sulfur atom that can comprise substitute(s); each among a, b and c represents position of carbon atom under condition that: (i) substitute(s) is chosen from the group comprising halogen atom, -OH, (C1-C6)-alkyl, mercapto-group, (C1-C6)-alkoxy-group, -NO2, -COOH, -CF3, phenyl, -NH2, (C1-C8)-linear or branched alkoxycarbonyl group, (C1-C8)-linear or branched acyl group, (C1-C8)-linear or branched acyloxy-group; (ii) when B represents benzene ring, each among -X- and -Y- represents -NH-, -Z- represents -CH2- and -W- represents -NH- then R2, R3 and R4 can not mean phenyl group, 4-bromophenyl group, 4-hydroxyphenyl group, 4-methoxyphenyl group, 2-hydroxyphenyl group, 3,4-dimethoxyphenyl group or 3-methoxy-4-hydroxyphenyl group. Compounds of the formula (I) show the enhanced capacity for transport of sugar and can be used in pharmaceutical compositions for prophylaxis and/or treatment of diabetes mellitus and diabetic nephropathy.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 21 tbl, 54 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention relates to a compound of the general formula [I]: wherein R1 and R2 can be similar or different and each represents (C1-C10)-alkyl group; each among R3 and R4 represents hydrogen atom; R5 and R6 can be similar or different and each represents hydrogen atom or (C1-C10)-alkyl group; Y represents 5-6-membered aromatic heterocyclic group or condensed aromatic heterocyclic group comprising one or some heteroatoms chosen from nitrogen atom, oxygen atom and sulfur atom wherein heterocyclic group can be substituted with 0-6 of similar or different groups chosen from the following group of substitutes α, and so on; n means whole values from 0 to 2; [Group of substitutes α]: hydroxyl group, halogen atoms, (C1-C10)-alkyl groups, (C1-C10)-alkyl groups wherein each group is monosubstituted with group chosen from the following group of substitutes β, (C1-C4)-halogenalkyl groups, (C3-C8)-cycloalkyl groups, (C1-C10)-alkoxy-groups, (C1-C10)-alkoxy-groups wherein each group is monosubstituted with group chosen from the following group of substitutes and so on; [Group of substitutes β]: hydroxyl group, (C3-C8)-cycloalkyl groups that can be substituted with halogen atom or alkyl group, (C1-C10)-alkoxy-group, (C1-C10)-alkylthio-groups, (C1-C10)-alkylsulfonyl groups, (C1-C10)-alkoxycarbonyl groups, amino-group, carbamoyl group (wherein its nitrogen atom can be substituted with similar or different (C1-C10)-alkyl groups), (C1-C6)-acyl groups, (C1-C10)-alkoxyimino-groups, cyano-group, optionally substituted phenyl group; [Group of substitutes γ]: optionally substituted phenyl group, optionally substituted aromatic heterocyclic groups, cyano-group. Also, invention relates to herbicide comprising derivative of isoxazoline of the formula [I] as an active component or its pharmaceutically acceptable salt. Invention provides the development of isoxazoline derivative possessing the herbicide activity with respect to resistant weeds, selectivity for cultural crop and weed.

EFFECT: valuable herbicide properties of substances.

18 cl, 24 tbl, 106 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new 2-amino-4-acetyl-7-bromo-8b-hydroxy-3a,8b-dihydroxytiazolo[5,4-b]indole of formula useful in liver protection from poisoning with carbon tetrachloride. Said compound has boiling point of 174-175°C (decomposition) and LD50 of 1950±180 mg/kg. Method for production of claimed compound also is disclosed.

EFFECT: new compound for liver protection from poisoning with carbon tetrachloride.

2 ex, 1 tbl

FIELD: organic chemistry, medicine, pulmonology.

SUBSTANCE: invention relates to a new chemical compound, namely, 7-bromo-4-acetylthiazolo[5,4-b]indol-2-succinimide of the formula: that is able to protect body against hypoxia and possesses the curative effect in lung toxic edema. The melting point of this compound is 267-269°.

EFFECT: valuable medicinal properties of compound.

2 tbl, 1 ex

FIELD: organic chemistry, medicine, pulmonology.

SUBSTANCE: invention relates to a new chemical substance, namely, 4-acetylthiazolo[5,4-b]indol-2-succinimide of the formula: that is able to protect body against hypoxia and possesses the prophylactic effect in lung toxic edema. The melting point of this substance is 264-265°C.

EFFECT: valuable medicinal properties of compound.

2 tbl, 1 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula 1 (G1 is group of general formulae 2 G1 is group of general formulae ; meanings of the rest substituents are as described in specification) or pharmaceutically acceptable salts thereof and use thereof in srug production. Said compounds are useful in treatment of male and female sexual disorders.

EFFECT: new oxytocin antagonists.

30 cl, 177 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula I and pharmaceutically acceptable salt thereof, wherein R1, R3, R4, R5, and R10 are independently H, halogen, C1-C4-alkyl, etc.; R2 is H, halogen, NO2, etc.; R6 is H, C1-C6-alkyl, C1-C6-alkoxy-substituted C1-C4-alkyl, etc.; R7 is H, C1-C4-alkyl or C2-C4-alkenyl, optionally substituted with halogen; R8 and R9 are H, R11 and R12; meanings of the rest substituents are as define in specification.

EFFECT: new compounds with value biological properties and useful as drug having activity in relates to progesterone receptor.

15 cl, 3 tbl, 80 ex

FIELD: organic chemistry.

SUBSTANCE: invention relates to new method for production of E-2-aroylmethylene-1-phenyl-1,2,3,4-tetrahydroquinazolin-4-ones of general formula I wherein R represents H, methyl, Cl. Claimed method includes interaction of 5-aryl-2,3-dihydro-2,3-furandiones with N-phenylanthranyl acid amide in medium of inert aprotic solvent (preferably benzene) followed by isolation of target products. Process is carried out preferably at 79-80°C. Claimed compounds have fluorescent properties and are useful in labeling and copying agents, intermediates for synthesis of new heterocyclic compounds, etc.

EFFECT: new fluorescent compounds.

3 cl, 1 dwg, 3 ex

FIELD: organic chemistry, antibacterial agents.

SUBSTANCE: invention relates to an agent used against acid-resistant microorganisms containing derivative of pyridone carboxylic acid as an active component, its pharmaceutically acceptable salt or its hydrate that elicits high antibacterial activity against Mycobacterium tuberculosis and atypical acid-resistant microorganisms. Invention describes agent used against acid-resistant microorganisms containing compound represented by the following formula (I) its salt or its hydrate as an active component wherein R1 represents cyclic alkyl group comprising 3-6 carbon atoms that can comprise substitute(s) chosen from halogen atom; R2 represents hydrogen atom; R3 represents hydrogen atom; A1 represents incomplete structure represented by the formula (2): wherein X2 represents halogen atom, alkyl group comprising 1-6 carbon atoms or alkoxy-group comprising 1-6 carbon atoms; A1, A2 and A3 form incomplete structure of the formula: in common with carbon atoms combined with them; X1 represents halogen atom; Y represents hydrogen atom; Z represents phenylpiperazine substitute. Invention provides synthesis of pyridone carboxylic acid eliciting high antibacterial activity against Mycobacterium tuberculosis and atypical acid-resistant microorganisms in combination with good pharmacokinetics indices and safety.

EFFECT: valuable biological property of agent.

10 cl, 9 tbl, 10 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to a synthetic quinolone agent that is effective as medicinal agents, veterinary preparations, drugs used in fishing industry or as antibacterial preserving agents. Invention describes compound represented by the following general formula (I): as its separate isomers or their mixture, its salt and their hydrates wherein R1 represents cyclic alkyl group comprising 3-6 carbon atoms that can comprise a substitute chosen from halogen atom; R2 represents hydrogen atom; R3 represents hydrogen atom; R4 represents hydrogen atom, amino-group, hydroxyl group; A represents nitrogen atom or part of structure as given in the invention claim; each R5 and R6 represents independently alkyl group comprising 1-6 carbon atoms or hydrogen atom; n means a whole number 1 or 2. Also, invention describes antibacterial agent and therapeutic agent based on compounds of the formula (I) used in treatment of infectious disease, a method for preparing antibacterial agent, a method for preparing a medicinal agent used in treatment of infectious disease and using compound of the formula (I) for preparing an antibacterial agent and using compound of the formula (I) for preparing a medicinal agent used in treatment of infectious disease. Invention provides novel compounds possessing useful biological properties.

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

35 cl, 2 tbl, 15 ex

FIELD: chemistry of heterocyclic compounds, antibacterial agents.

SUBSTANCE: invention relates to agent used against acid-resistant microorganisms. Invention describes agent against acid-resistant microorganisms containing as an active component the compound represented by the general formula (1) or its hydrate wherein R2 represents hydrogen atom; R3 represents hydrogen atom; A1, A2 and A3 form incomplete structure of the formula: wherein A1 represent incomplete structure of the formula: wherein X2 and above described R1 can be combined to form six-membered cyclic structure comprising part of the parent nucleus wherein formed ring can comprise oxygen atom and, except for, can comprise alkyl group having 1-6 carbon atoms as a substitute; X1 represents halogen atom, hydrogen atom or amino-group; Y represents hydrogen atom; Z represents incomplete structure of the formula: . Agent elicits high antibacterial activity of broad spectrum and possesses good pharmacokinetics and safety also.

EFFECT: improved and valuable properties of agent.

3 cl, 9 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel lactam compounds of the formula (I) or their pharmaceutically acceptable salts wherein A means phenyl, thienyl, pyridyl, pyrimidinyl, pyrazinyl; R2, R3 and R4 can be similar or different and mean independently of one another hydrogen atom (H), halogen atom, -OH, (C1-C6)-alkyl, (C1-C6)-alkoxy-group, -NH2, -NO2, -CF3, phenyl that can comprise substitute(s), benzyloxy-group that can comprise substitute(s), pnehylvinyl, and one among R2, R3 and R4 means -CF3-O- and others mean H; B means phenyl that can comprises substitute(s), monocyclic aliphatic (C3-C8)-ring, dihydropyrane ring; -X- and -Y- xan be similar or different and they mean independently -O-, -NH-, -NR5-, -S-; Z means -CH2-, -NH-; W means -NR1-, -CR8R9- wherein R1 means H; R8 and R9 are similar or different and mean H; wherein R5 represents a linear alkyl group that can comprise substitute(s), (C1-C8)-linear or branched alkoxycarbonyl group, acyl group chosen from formyl group, acyl group comprising (C1-C6)-alkyl, (C1-C6)-alkenyl or (C1-C6)-alkynyl group that can comprise substitute(s), carbamoyl group comprising (C1-C6)-alkyl group at nitrogen atom that can comprise substitutes, sulfonyl group comprising (C1-C6)-alkyl group at sulfur atom that can comprise substitute(s); each among a, b and c represents position of carbon atom under condition that: (i) substitute(s) is chosen from the group comprising halogen atom, -OH, (C1-C6)-alkyl, mercapto-group, (C1-C6)-alkoxy-group, -NO2, -COOH, -CF3, phenyl, -NH2, (C1-C8)-linear or branched alkoxycarbonyl group, (C1-C8)-linear or branched acyl group, (C1-C8)-linear or branched acyloxy-group; (ii) when B represents benzene ring, each among -X- and -Y- represents -NH-, -Z- represents -CH2- and -W- represents -NH- then R2, R3 and R4 can not mean phenyl group, 4-bromophenyl group, 4-hydroxyphenyl group, 4-methoxyphenyl group, 2-hydroxyphenyl group, 3,4-dimethoxyphenyl group or 3-methoxy-4-hydroxyphenyl group. Compounds of the formula (I) show the enhanced capacity for transport of sugar and can be used in pharmaceutical compositions for prophylaxis and/or treatment of diabetes mellitus and diabetic nephropathy.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 21 tbl, 54 ex

FIELD: organic chemistry, herbicides.

SUBSTANCE: invention relates to a compound of the general formula [I]: wherein R1 and R2 can be similar or different and each represents (C1-C10)-alkyl group; each among R3 and R4 represents hydrogen atom; R5 and R6 can be similar or different and each represents hydrogen atom or (C1-C10)-alkyl group; Y represents 5-6-membered aromatic heterocyclic group or condensed aromatic heterocyclic group comprising one or some heteroatoms chosen from nitrogen atom, oxygen atom and sulfur atom wherein heterocyclic group can be substituted with 0-6 of similar or different groups chosen from the following group of substitutes α, and so on; n means whole values from 0 to 2; [Group of substitutes α]: hydroxyl group, halogen atoms, (C1-C10)-alkyl groups, (C1-C10)-alkyl groups wherein each group is monosubstituted with group chosen from the following group of substitutes β, (C1-C4)-halogenalkyl groups, (C3-C8)-cycloalkyl groups, (C1-C10)-alkoxy-groups, (C1-C10)-alkoxy-groups wherein each group is monosubstituted with group chosen from the following group of substitutes and so on; [Group of substitutes β]: hydroxyl group, (C3-C8)-cycloalkyl groups that can be substituted with halogen atom or alkyl group, (C1-C10)-alkoxy-group, (C1-C10)-alkylthio-groups, (C1-C10)-alkylsulfonyl groups, (C1-C10)-alkoxycarbonyl groups, amino-group, carbamoyl group (wherein its nitrogen atom can be substituted with similar or different (C1-C10)-alkyl groups), (C1-C6)-acyl groups, (C1-C10)-alkoxyimino-groups, cyano-group, optionally substituted phenyl group; [Group of substitutes γ]: optionally substituted phenyl group, optionally substituted aromatic heterocyclic groups, cyano-group. Also, invention relates to herbicide comprising derivative of isoxazoline of the formula [I] as an active component or its pharmaceutically acceptable salt. Invention provides the development of isoxazoline derivative possessing the herbicide activity with respect to resistant weeds, selectivity for cultural crop and weed.

EFFECT: valuable herbicide properties of substances.

18 cl, 24 tbl, 106 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using phenylethenyl- or phenylethynyl-derivatives as antagonists of glutamates receptors. Invention describes using compound of the general formula (I):

wherein each among R1, R2, R3, R4 and R5 means independently of one another hydrogen atom, (C1-C6)-alkyl, -(CH2)n-halogen, (C1-C6)-alkoxy-group, -(CH2)n-NRR', -(CH2)n-N(R)-C(O)-C1-C6)-alkyl, phenyl or pyrrolyl that can be unsubstituted or substituted with one or more (C1-C6)-alkyl; each among R, R' and R'' means independently of one another hydrogen atom or (C1-C6)-alkyl; A means -CH=CH- or C≡C; B means ,, , , or wherein R6 means hydrogen atom, (C1-C)-alkyl, -(CH2)n-C(O)OR, or halogen atom; R7 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-C(O)OR', halogen atom, nitro-group or oxodiazolyl group that can be unsubstituted or substituted with (C1-C6)-alkyl or cycloalkyl; R8 means hydrogen atom, (C1-C6)-alkyl, -(CH2)n-OH, -(CH2)n-C(O)OR'' or phenyl; R9 means (C1-C6)-alkyl; R10 and R11 mean hydrogen atom; R12 means -(CH2)n-N(R)-C(O)-(C1-C6)-alkyl; R13 means hydrogen atom; each R14, R15, R16 and R17 independently of one another means hydrogen atom or (C1-C6)-alkoxy-group; each R18, R19 and R20 independently of one another means hydrogen atom; R21 means hydrogen atom or (C1-C6)-alkyl; R22 means hydrogen atom, (C1-C6)-alkyl or (C1-C6)-alkyl comprising one or more substitutes chosen from groups hydroxy- or halogen atom; R23 means hydrogen atom, (C1-C6)-alkanoyl or nitro-group; each among R24, R25 and R26 independently of one another means hydrogen atom or (C1-C6)-alkyl; n = 0, 1, 2, 3, 4, 5 or 6; X means -O- or -S-; Y means -CH= or -N=, and its pharmaceutically acceptable salts used in preparing medicinal agents designates for treatment or prophylaxis of disorders mediated by mGluR5-receptors. Also, invention describes compounds of the formula (I-A), compound of the formula (I-B-1) given in the invention description, and a medicinal agent used in treatment or prophylaxis of disorders mediated by mGluR5-receptors.

EFFECT: valuable medicinal properties of compounds.

44 cl, 1 tbl, 44 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel anellated carbamoylazaheterocycles of the general formula (1) that possess inhibitory property of kinase activity and eliciting, for example, an anticancer activity. Also, compounds can be used as agonists, antagonists, receptor modulating agents, antiparasitic and antibacterial agents. Also, invention relates to a method for synthesis of compounds of the formula (1), a pharmaceutical composition based on thereof and a focused library for assay of leader-compounds. In compounds of the general formula (1) W represents 6-oxopiperazine, [1,4]-thiazepane, [1,4]-oxazepane or [1,4]-diazepane cycle anellated with at least one optionally substituted and optionally condensed heterocycle or carbocycle Q; Q represents optionally substituted thiophene, optionally substituted pyrrole, optionally substituted imidazole, optionally substituted thiazole, optionally substituted pyrrolidine, optionally substituted indole, optionally substituted benzofuran, optionally substituted pyridine, optionally substituted quinoline, optionally substituted benzene or optionally substituted naphthalene cycle; R1, R2 and R represent independently of each another hydrogen atom, inert substitute, optionally substituted (C1-C6)-alkyl, optionally substituted (C3-C8)-cycloalkyl, optionally substituted phenyl, optionally substituted aryl, optionally substituted heterocyclyl.

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

15 cl, 5 tbl, 6 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

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