Pyrrolo- and thiazolopyridine compounds (versions) and based pharmaceutical composition

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes the pyrrolo- and thiazolopyridinium compounds and their pharmaceutically acceptable salts covered by general structural formula I: wherein the values A, B, R1, R2, R3, R4, R5, R6, R7 and R8 are those as presented in cl.1, and a pharmaceutical composition based on the given compound for inhibition of hypoxia-inducible factor (HIF) hydroxylase activity.

EFFECT: there are produced and described new compounds able to modulate hypoxia-inducible factor (HIF) stability and/or activity.

29 cl, 178 ex

 

The text descriptions are given in facsimile form.

1. Connection pyrrole and triazolopyridine covered by the General structural formula I:

where a and b are independently selected from the group including =C(R7)-, -N(R8)-, =N - and-S - execution of at least one of the following conditions:
But a =C(R7)-and represents-N(R8)-;
And represents-S-, and b is a =N;
And represents =N-and represents-S-; or
And represents-N(R8)but there is a =C(R7)-;
one ofandhas a double bond and the other is a single bond;
R1represents a hydroxyl;
R2selected from the group comprising hydrogen and methyl;
R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, halogen, cyano, C1-C10-alkyl, C1-C10-alkyl, substituted Deputy selected from the group comprising From6-C14-aryl and C1-C10-and what kiltie, With2-C6alkenyl, substituted C6-C14-aryl, C2-C6-quinil,6-C14-aryl, C6-C14aryl, substituted Deputy, selected from the group consisting of cyano and C1-C10-heterocyclyl containing 1-4 heteroatoms selected from the group comprising N, S or O1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S or O, C1-C10-heterocyclyl containing 1-4 heteroatoms selected from the group comprising N, S or O, and C1-C15-acyl containing 0-4 heteroatoms selected from the group comprising N, S or O;
R6and R7each independently selected from the group comprising hydrogen, halogen, cyano, C1-C10-alkyl, C6-C14-aryl, C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen, cyano, C1-C10-alkoxy, C6-C14-aryloxy,6-C14-aryl, C1-C10-alkyl and C1-C10-alkyl, substituted by at least one halogen atom, With6-C14-aryloxy,1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S or O1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S and O, substituted Deputy selected from g is uppy, including halogen, C1-C10-alkoxy, C6-C14-aaltio and benzyl, amino, substituted by one or two substituents selected from the group comprising From1-C10-alkyl and C6-C14-aryl;
or, if a or b is a =C(R7)-, R6and R7together with the carbon atoms to which they are linked, With6-C14-aryl; and
R8selected from the group comprising From1-C10-alkyl, C1-C10-alkyl, substituted Deputy selected from the group comprising From3-C10-cycloalkyl,6-C14-aryl or C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen or1-C14-alkoxy, C2-C6alkenyl, substituted C6-C14-aryl, C6-C14-aryl and C6-C14aryl, substituted Deputy, selected from the group comprising halogen and C1-C10-alkoxy;
or their pharmaceutically acceptable salts.

2. Compounds according to claim 1, in which R2represents hydrogen,

3. Compounds according to claim 1, in which R2represents methyl.

4. Compounds according to claim 1, in which R5selected from the group comprising hydrogen, C1-C10-alkyl, cyano, halogen and C6-C14-aryl.

5. Compounds according to claim 4, in which R5selected from g is PI, including hydrogen, cyano, methyl, ethyl, propyl, butyl, chlorine and phenyl.

6. Compounds according to claim 1, in which R5selected from the group comprising hydrogen, cyano, C1-C10-alkyl, C1-C10-alkyl, substituted Deputy selected from the group comprising From6-C14-aryl and C1-C10-alkylthio,2-C6alkenyl, substituted C6-C14-aryl, C2-C6-quinil,6-C14-aryl, C6-C14aryl, substituted Deputy, selected from the group consisting of cyano and C1-C10-heterocyclyl containing 1-4 heteroatoms selected from the group comprising N, S or O1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S or O1-C10-heterocyclyl containing 1-4 heteroatoms selected from the group comprising N, S or O, and C1-C15-acyl containing 0-4 heteroatoms selected from the group comprising N, S or O.

7. Compounds according to claim 1, in which R5selected from the group comprising hydrogen, cyano, acetyl, methyl, ethyl, propyl, butyl, benzyl, phenethyl, ethinyl, still, isopropylaminomethyl, phenyl, 4-cyano-phenyl, furan-2-yl, thiazol-2-yl and piperidine-1-yl.

8. Compounds according to claim 1, in which R6selected from the group comprising hydrogen, chlorine, bromine, cyano, methyl, propyl, tert-butyl, phenyl, 4-chlorophenyl and 4-forfinal.

6selected from the group comprising methyl, tert-butyl, phenyl, 4-cyanophenyl, 4-tert-butylphenyl, triptoreline, 3-chloro-4-forfinal, 4-chlorophenyl, 4-forfinal, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, biphenyl-4-yl, 4-phenoxyphenyl, phenoxy, naphthalene-2-yl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydro-benzofuran-5-yl, dibenzofuran-4-yl, pyridine-2-yl, pyridin-3-yl, 6-chloropyridin-3-yl, 5-bromopyridin-3-yl, 6-butoxypropan-3-yl, quinoline-3-yl, 6-phenylsulfanyl-pyridine-3-yl, pyrimidine-5-yl, thiophene-2-yl, benzo[b]thiophene-2-yl, benzo[b]thiophene-3-yl, furan-2-yl, benzofuran-2-yl, 1-benzyl-1H-pyrazole-4-yl and 2-benzyl-2H-pyrazole-3-yl.

10. Compounds according to claim 1, in which a is a =C(R7)-, a R7selected from the group comprising hydrogen, halogen, cyano, C1-C10-alkyl and C6-C14-aryl.

11. Compounds according to claim 1, in which a is a =C(R7)-, and R7selected from the group comprising hydrogen, chlorine, bromine, cyano, methyl, propyl, tert-butyl and phenyl.

12. Compounds according to claim 1, which represents-N(R8)-, a R8selected from the group comprising From1-C10-alkyl, C1-C10-alkyl, substituted Deputy selected from the group comprising From3-C10-cycloalkyl,6-C14-aryl or C6-C14is aryl, substituted by one or two substituents selected is from the group including halogen, C1-C10-alkoxy, C2-C6alkenyl, substituted C6-C14-aryl, C6-C14-aryl and C6-C14aryl, substituted Deputy, selected from the group comprising halogen and C1-C10-alkoxy.

13. Compounds according to claim 1, which represents-N(R8)-, a R8selected from the group comprising methyl, n-propyl, tert-butyl, 3-methylbutyl, 1-cyclohexylmethyl, phenethyl, (R)-1-phenylethyl, (S)-1-phenylethyl, phenyl, 4-methoxyphenyl, 4-forfinal, benzyl, 2-tormentil, 3-tormentil, 4-tormentil, 3,4-diferensial, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl and benzo[1,3]-dioxol-5-ylmethyl.

14. Compounds according to claim 1, in which a is a =C(R7)-, R6and R7together with the carbon atoms to which they are linked, form a6-C14-aryl group.

15. Connection 14, in which6-C14-aryl group represents phenyl.

16. Compounds according to claim 1, in which
But a =C(R7)-;
Represents a-N(R8)-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, halogen, cyano, C1-C10-alkyl and C6-C14-aryl;
R6selected from the group comprising hydrogen, halogen, cyano, C1-sub> 10-alkyl, C6-C14-aryl, C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen, cyano, C1-C10-alkoxy, C6-C14-aryloxy,6-C14-aryl, C1-C10-alkyl and C1-C10-alkyl, substituted by at least one halogen atom, With6-C14-aryloxy, amino, substituted by one or two substituents selected from the group comprising C1-C10-alkyl and C6-C14-aryl, C1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S or O and C1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S and O, substituted Deputy selected from the group comprising halogen, C1-C10-alkoxy, C6-C14-aaltio and benzyl;
R7selected from the group comprising hydrogen, halogen, cyano, C1-C10-alkyl, C6-C14-aryl; and
R8selected from the group comprising From1-C10-alkyl, C1-C10-alkyl, substituted Deputy selected from the group comprising From3-C10-cycloalkyl,6-C14-aryl or C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen, C1-C10-alkoxy, C2-C6-al is Anil, replaced With6-C14-aryl, C6-C14-aryl and C6-C14aryl, substituted Deputy selected from the group comprising halogen and C1-C10-alkoxy.

17. Compounds according to claim 1, in which
But a =C(R7)-;
Represents a-N(R8)-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, halogen, cyano, C1-C10-alkyl and C6-C14-aryl;
R8selected from the group comprising C1-C10-alkyl, C6-C14-aryl and C6-C14aryl, substituted Deputy selected from the group comprising halogen and C1-C10-alkoxy; and
R6and R7together with the carbon atoms to which they are linked, form a6-C14-aryl group.

18. Connection 17 in which R5represents hydrogen, cyano, methyl or phenyl, and R8represents a methyl or phenyl.

19. Compounds according to claim 1, in which
But a =C(R7)-;
Represents a-N(R8)-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, chlorine, cyano, methyl, ethyl and phenyl;
R6selected from the group comprising water is od chlorine, bromine, cyano, methyl, propyl, tert-butyl, phenyl, 4-chlorophenyl and 4-forfinal;
R7selected from the group comprising hydrogen, chlorine, bromine, cyano, methyl, propyl, tert-butyl and phenyl, and
R8selected from the group comprising hydrogen, methyl, 3-methylbutyl, 1-cyclohexylmethyl, phenethyl, (R)-1-phenylethyl, (S)-1-phenylethyl, phenyl, 4-methoxyphenyl, 4-forfinal, benzyl, 2-tormentil, 3-tormentil, 4-tormentil, 3,4-diferensial, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl and benzo[1,3]-dioxol-5-ylmethyl.

20. Compounds according to claim 1, in which
But a =C(R7)-;
Represents a-N(R8)-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5represents cyano;
R6selected from the group comprising hydrogen, chlorine and bromine;
R7selected from the group comprising hydrogen, methyl, chloro, bromo, and phenyl; and
R8selected from the group comprising phenethyl, (R)-1-phenylethyl, (S)-l-phenylethyl, phenyl, 4-methoxyphenyl, 4-forfinal, benzyl, 2-tormentil, 4-tormentil, 2-methoxybenzyl and 4-methoxybenzyl.

21. Compounds according to claim 1, in which
And represents-S-;
In represents =N-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, cyano, C1-C10-alkyl, C -C10-alkyl, substituted Deputy selected from the group comprising From6-C14-aryl and C1-C10-alkylthio,2-C6alkenyl, substituted C6-C14-aryl, C2-C6-quinil,6-C14-aryl, C6-C14aryl, substituted Deputy, selected from the group consisting of cyano and C1-C10-heterocyclyl containing 1-4 heteroatoms selected from the group comprising N, S or O1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S or O, C1-C10-heterocyclyl containing 0-4 heteroatoms selected from the group comprising N, S or O, and C1-C15-acyl containing 0-4 heteroatoms selected from the group comprising N, S or O, and
R6selected from the group comprising hydrogen, C1-C10-alkyl, C6-C14-aryl, C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen, cyano, C1-C10-alkoxy, C6-C14-aryloxy,6-C14-aryl, C1-C10-alkyl and C1-C10-alkyl, substituted by at least one halogen atom, With6-C14-aryloxy, amino, substituted by one or two substituents selected from the group comprising C1-C10-alkyl and C6-C14-aryl, C1-C15-heteroaryl, containing 1-4 heteroatoms selected from the group comprising N, S or O and C1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S and O, substituted Deputy selected from the group comprising halogen, C1-C10-alkoxy, C6-C14-aaltio and benzyl.

22. Compounds according to claim 1, in which
And represents-S-;
In represents =N-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen or methyl;
R5selected from the group comprising hydrogen, cyano, acetyl, methyl, ethyl, propyl, butyl, phenethyl, ethinyl, still, isopropylaminomethyl, phenyl, 4-cyanophenyl, furan-2-yl, thiazol-2-yl and piperidine-1-yl; and
R6selected from the group comprising methyl, tert-butyl, phenyl, 4-cyanophenyl, 4-tert-butylphenyl, triptoreline, 3-chloro-4-forfinal, 4-chlorophenyl, 4-forfinal, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, biphenyl-4-yl, 4-phenoxyphenyl, phenoxy, naphthalene-2-yl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, 2,3-dihydrobenzofuran-5-yl, dibenzofuran-4-yl, pyridine-2-yl, pyridin-3-yl, 6-chloropyridin-3-yl,
5-bromopyridin-3-yl, 6-butoxypropan-3-yl, quinoline-3-yl, 6-phenylalaninamide-3-yl, pyrimidine-5-yl, thiophene-2-yl, benzo[b]thiophene-2-yl, benzo[b]thiophene-3-yl, furan-2-yl, benzofuran-2-yl, 1-benzyl-1H-pyrazole-4-yl and 2-benzyl-2H-pyrazole-3-yl.

23. Compounds according to claim 1,in which
And represents-S-;
In represents =N-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, methyl, ethyl, butyl and phenyl; and
R6represents phenyl.

24. Compounds according to claim 1, in which
But a =N;
In represents-S-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, C1-C10-alkyl and C6-C14-aryl; and
R6selected from the group comprising hydrogen, C1-C10-alkyl, C6-C14-aryl, C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen, cyano, C1-C10-alkoxy, C6-C14-aryloxy,6-C14-aryl, C1-C10-alkyl and C1-C10-alkyl, substituted by at least one halogen atom, With6-C14-aryloxy, amino, substituted by one or two substituents selected from the group comprising From1-C10-alkyl and C6-C14-aryl, C1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N, S or O and C1-C15-heteroaryl containing 1-4 heteroatoms selected from the group comprising N,S or O, replaced by Deputy selected from the group comprising halogen, C1-C10-alkoxy, C6-C14-aaltio and benzyl.

25. Connection point 24, in which R5selected from the group comprising hydrogen, methyl, benzyl, phenyl and 4-morpholine-4-ylphenyl, and R6represents phenyl.

26. Compounds according to claim 1, in which
And represents-N(R8)-;
Represents a =C(R7)-;
R1represents a hydroxyl;
R2, R3and R4represent hydrogen;
R5selected from the group comprising hydrogen, cyano, and C1-C10-alkyl;
R6and R7selected from the group comprising hydrogen and halogen;
or R6and R7together with the carbon atoms to which they are linked, form a6-C14-aryl group, and
R8selected from the group comprising hydrogen, C1-C10-alkyl, C1-C10-alkyl, substituted Deputy selected from the group comprising From3-C10-cycloalkyl,6-C14-aryl or C6-C14is aryl, substituted by one or two substituents selected from the group comprising halogen, C1-C10-alkoxy, C2-C6alkenyl, substituted C6-C14-aryl, and C6-C14-aryl.

27. Connection pyrrole and triazolopyridine selected from the group including:
[(2-bromo-4-Ki-the Roxy-1-phenyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(2,3-dibromo-4-hydroxy-1-phenyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino] -acetic acid,
{[3-bromo-4-hydroxy-1-phenyl-2-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-2,3-dibromo-4-hydroxy-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1-phenyl-2-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
[(1-benzyl-4-hydroxy-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
{[3-bromo-4-hydroxy-1,2-bis-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-uxasuu acid,
{[4-hydroxy-1,2-bis-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1,2-bis-(4-fluoro-phenyl)-3-chloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[3-bromo-4-hydroxy-1-(4-methoxy-phenyl)-2-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1-(4-methoxy-phenyl)-2-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[2-bromo-4-hydroxy-3-phenyl-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-3-phenyl-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-3-phenyl-1-(4-fluoro-phenyl)-7-chloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic is islote,
{[4-hydroxy-7-methyl-3-phenyl-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[3-bromo-2-tert-butyl-4-hydroxy-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[2-tert-butyl-4-hydroxy-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-4-hydroxy-2,3-dimethyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[2,3-dibromo-4-hydroxy-1-methyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1,2,3-trimethyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[2-bromo-3-tert-butyl-4-hydroxy-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[3-tert-butyl-4-hydroxy-1-(4-fluoro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-4-hydroxy-2,3-dipropyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-4-hydroxy-3,7-dichloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
[(4-hydroxy-9-phenyl-N-beta carboline-3-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-methyl-9-phenyl-N-beta carboline-3-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1,9-diphenyl-N-beta carboline-3-carbonyl)-amino]-acetic acid,
{[1-benzyl-4-hydroxy-7-methyl-3-chloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-4-hydroxy-7-phenyl-3-chloro-1H-p is Rolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-4-hydroxy-3-chloro-7-ethyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1,3-diphenyl-2-(4-forfinal)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1-phenyl-3-chloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-7-methyl-1-phenyl-3-chloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-(benzo[1,3]dioxol-5-ylmethyl)-3-bromo-4-hydroxy-2-(4-chloro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[3-bromo-4-hydroxy-1-phenyl-2-(4-chloro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-(benzo[1,3]dioxol-5-ylmethyl)-4-hydroxy-2-phenyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-(benzo[1,3]dioxol-5-ylmethyl)-4-hydroxy-2-(4-chloro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzo[1,3]dioxol-5-ylmethyl-4-hydroxy-3-methyl-2-(4-chloro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1,2-diphenyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-3-methyl-1-phenyl-2-(4-chloro-phenyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
[(7-hydroxy-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2,4-diphenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-methyl-2-phenyl-thiazolo[4,5-C]pyrid the n-6-carbonyl)-amino]-acetic acid,
(S)-2-[(7-hydroxy-4-methyl-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-propionic acid,
[(7-hydroxy-2-(4-trifluoromethyl-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-chloro-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-methoxy-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-fluoro-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-4-ethyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenoxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(methyl-phenyl-amino)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(phenylamino)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-thiazolo[5,4-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-(5-bromo-pyridine-3-yl)-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-pyridin-3-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(4-butyl-7-hydroxy-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-pyridin-2-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-methyl-2-(4-fluoro-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-propyl-2-phenyl-is Iesolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-phenoxy-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-4-cyano-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(4-isobutyl-7-hydroxy-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(3-methoxy-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-4-furan-2-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-thiazol-2-yl-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(2-methoxy-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-methyl-2-phenyl-thiazolo[5,4-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-cyano-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2,4-diphenyl-thiazolo[5,4-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-fluoro-3-chloro-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(4-benzyl-7-hydroxy-2-phenyl-thiazolo[5,4-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-(4-(morpholine-4-yl-phenyl)-2-phenyl-thiazolo[5,4-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-4-(4-cyano-phenyl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(4-fluoro-phenyl)-4-cyano-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic KIS the GTC,
[(7-hydroxy-2-(3-methoxy-phenyl)-4-cyano-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-4-cyano-thiazolo[5,4-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-phenyl-4-ethinyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(4-acetyl-7-hydroxy-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-4-piperidine-1-yl-2-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-(4-tert-butyl-phenyl)-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-benzo[b]thiophene-3-yl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-biphenyl-4-yl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-benzo[b]thiophene-2-yl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-quinoline-3-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-benzofuran-2-yl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-dibenzofuran-4-yl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-(2,3-dihydro-benzofuran-5-yl)-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-pyrimidine-5-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-and the Ino]-acetic acid,
[(2-(1-benzyl-1H-pyrazole-4-yl)-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(6-chloro-pyridine-3-yl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-(6-butoxy-pyridine-3-yl)-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-(6-phenylsulfanyl-pyridine-3-yl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-(1-benzyl-1H-pyrazole-4-yl)-7-hydroxy-4-cyano-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
{[4-hydroxy-1-(3-methyl-butyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1-(3-methyl-butyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1-(3-methyl-butyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-2,3-dichloro-7-cyano-1-cyclohexylmethyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-7-cyano-1-cyclohexylmethyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[1-benzyl-4-hydroxy-3-chloro-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
[(4-hydroxy-9-methyl-N-beta carboline-3-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1,9-dimethyl-N-beta carboline-3-carbonyl)-amino]-acetic acid,
[(4-hydroxy-9-methyl-1-phenyl-N-beta carboline-3-carbonyl)-amino]-acetic acid,
[(4-hydroc and-9-methyl-1-cyano-N-beta carboline-3-carbonyl)-amino]-acetic acid,
{[3-bromo-4-hydroxy-1-phenyl-2-(4-fluoro-phenyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
{[4-hydroxy-1-phenyl-2-(4-fluoro-phenyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl]-amino}-acetic acid,
[(4-hydroxy-5-phenyl-5H-pyrido[4,3-b]indole-3-carbonyl)-amino]-acetic acid,
[(4-hydroxy-5-phenyl-1-cyano-5H-pyrido[4,3-b]indole-3-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-methyl-5-phenyl-5H-pyrido[4,3-b]indole-3-carbonyl)-amino]-acetic acid,
[(1-benzyl-4-hydroxy-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-2-(4-fluoro-phenyl)-3-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-7-methyl-1-phenyl-2-(4-fluoro-phenyl)-3-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-(4-fluoro-phenyl)was 3.7-dicyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-3-chloro-7-Canon-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(2,3-dibromo-4-hydroxy-1-(4-fluoro-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenethyl-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(2,3-dibromo-4-hydroxy-1-(4-fluoro-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(3-bromo-4-hydroxy-1-phenyl-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-fluoro-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenethyl-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(2,3-dibromo-4-hydroxy-1-(1(3)-phenyl-ethyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-fluoro-benzyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(1-benzyl-4-hydroxy-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(18-phenyl-ethyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-2,3-dichloro-7-Sapo-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenethyl-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(18-phenyl-ethyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(1-benzyl-3-bromo-4-hydroxy-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-N-(1R-phenyl-ethyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-the UKS who scurry acid,
[(1-benzyl-4-hydroxy-3-methyl-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-benzyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(1R-phenyl-ethyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-benzyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-phenyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-phenyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-methoxy-phenyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-2,3-dimethyl-1-(4-fluoro-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-fluoro-phenyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-fluoro-phenyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-fluoro-phenyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(4-fluoro-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-phenyl-2-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(2-fluoro-benzyl)-1H-what irolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(2-methoxy-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-methoxy-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-3-phenyl-1-(4-fluoro-phenyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(2-fluoro-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(2-methoxy-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-methoxy-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-fluoro-benzyl)-2-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(2-fluoro-benzyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-fluoro-benzyl)-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(2-fluoro-benzyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-methoxy-benzyl)-3-chloro-7-cyano-1H-pyrrolo [2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-fluoro-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3,4-debtor-benzyl)-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3,4-debtor-benzyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-who]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-fluoro-benzyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3-fluoro-benzyl)-3-chloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(4-hydroxy-1-(3,4-debtor-benzyl)-2,3-dichloro-7-cyano-1H-pyrrolo[2,3-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(1-benzyl-7-hydroxy-2,3-dichloro-1H-pyrrolo[3,2-C]pyridine-5-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-4-methyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-4-cyano-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(4-butyl-2-tert-butyl-7-hydroxy-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-4-((E)-styryl)-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-4-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-4-phenethyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(2-tert-butyl-7-hydroxy-4-isopropylaminomethyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-methyl-4-phenyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-methyl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-NAF is Alin-2-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid,
[(7-hydroxy-2-thiophene-2-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid, and
[(7-hydroxy-2-furan-2-yl-thiazolo[4,5-C]pyridine-6-carbonyl)-amino]-acetic acid.

28. Pharmaceutical composition for inhibiting the activity of the hydroxylase hypoxia-inducible factor (HIF), comprising the compound according to claim 1 and a pharmaceutically acceptable filler.

29. The composition according to p, additionally comprising at least one additional therapeutic agent selected from the group comprising vitamin B12, folic acid, iron sulfate (II), recombinant erythropoietin and stimulator of erythropoiesis (ESA).



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I , and pharmaceutically acceptable salts thereof, where L denotes O, S, or CH2; Y denotes N or CH; Z denotes CR3; G denotes CH; R1 denotes a heteroaryl ring of formula , where D1 denotes S, O; D2 denotes N or CR12; D3 denotes CR12; R2 denotes (C6-C10)-aryl; 5-9-member mono- or bicyclic heteroaryl with 1 or 2 heteroatoms independently selected from N or S; a saturated or partially saturated (C3-C7)-cycloalkyl; or a saturated 5-6-member heteocyclyl with 1 heteroatom selected from N, where said aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted with one or two groups independently selected from (C1-C6)-alkyl, F, Cl, Br, CF3, CN, NO2, OR6, C(-O)R6, C(=O)OR6, C(=O)NR6R7, saturated 6-member heterocyclyl with 2 heteroatoms independently selected from N or O, and S(O)2R6, and where said alkyl is optionally substituted with one -OR8 group; R3 denotes H; (C1-C6)-alkyl; (C2-C6)-alkenyl; Cl; Br; OR6; SR6; phenyl; or a 6-member heteroaryl with 1 heteroatom selected from N, where said alkyl and alkenyl are optionally substituted with one group selected from C(=O)OR8, -OR8, -NR8R9; or a saturated 6-member heterocyclyl with 1 heteroatom selected from N or O.

EFFECT: disclosed compounds are used in treating and preventing diseases mediated by insufficient level of glucokinase activity, such as sugar diabetes.

16 cl, 479 ex

FIELD: chemistry.

SUBSTANCE: described are novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side with considerable absorption in the region up to 410-420 nm, having general formulae (a)-(k) (structural formula and values of radicals are given in the description), composition which is stabilised with respect to UV radiation and containing novel UV-absorbers, and use of the novel compounds as UV light stabilisers for organic materials.

EFFECT: obtaining novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side.

13 cl, 23 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives, having HIV replication inhibiting properties, or pharmaceutically acceptable salts thereof. In formula (1): R1 denotes hydrogen; R2 and R3 independently denote hydrogen; R7 and R8 denote C1-6alkyl; R4 denotes cyano; R9 denotes C1-6alkyl optionally substituted with cyano, C2-6alkenyl substituted with cyano, C2-6alkynyl optionally substituted with cyano; R5 denotes C1-6alkyl optionally substituted with Ar or Het; C2-6alkenyl optionally substituted with Ar or Het; C2-6alkynyl optionally substituted with Ar or Het; C3-7cycloalkyl; Ar; Het; R6 denotes H, Het; Y denotes -OR11, -NR12R13; R11 denotes hydrogen or C1-6alkyl optionally substituted with hydroxy, C1-6alkoxy or pyridyl; R12 denotes hydrogen or C1-6alkyl; R13 denotes hydrogen or C1-6alkyl; or R12 and R13 together with a nitrogen atom, which is substituted by said two substitutes, form a morpholinyl; imidazolyl; X denotes -NR1-; Het denotes 5- or 6-member completely saturated ring, where one or two ring members are heteroatoms, each independently selected from nitrogen and sulphur, and where the rest of the ring members are carbon atoms; and where any member of the heterocycle with a nitrogen heteroatom can optionally be substituted with C1-6alkyl; where the 5- or 6-member ring can optionally be annelated with a benzene or thiophene ring; each aryl independently denotes phenyl or phenyl substituted with one substitute selected from C1-6alkoxy.

EFFECT: high efficiency of using said compounds.

7 cl, 4 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: there are described substituted imidazo[2,1-b]thiazoles of general formula the R1, R1, R3 R4, M1, M2 radical values are presented in the patent claim cl. 1, as well as methods for making them, drug preparations containing these compounds and application of these compounds for making the drug preparations.

EFFECT: higher efficacy.

23 cl, 3 tbl, 25 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula

wherein: m, n, R0, R1, R2, R3 and R4 have the values presented in clause 1 of the patent claim provided the compound of formula (I) cannot represent N-methyl-1-(phenylsulphonyl)-1H-indole-4-methanamine.

EFFECT: compounds show 5-NT6 receptor antagonist activity that that allows them being used in the pharmaceutical composition.

19 cl, 3 tbl, 192 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel agents for controlling plant fungal diseases, specifically 3,7-dithia-1,5-diazabicyclo[3,3,0]octane as an agent against Bipolaris sorokiniana, Aspergillus fumigates, Aspergillus niger, synthesis of which takes place in a single step using readily available reactants in contrast to multi-step synthesis of existing agents used for controlling fungal diseases of plants and materials.

EFFECT: obtaining novel agents for controlling plant fungal diseases.

1 cl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel heteroaryl-substituted derivative of benzothiazole - 2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol where one or more atoms may be a detectable isotope, in form of a free base or pharmaceutically acceptable salt thereof, capable of binding with amyloid deposits, to pharmaceutical compositions based on the radioactive-labelled disclosed compound, to use of the detectable isotope-labelled disclosed compound for determining amyloid deposits, as well as use of the disclosed compound in producing a medicinal agent for preventing and/or treating Alzheimer's disease and familial Alzheimer's disease. The present invention also relates to a novel intermediate compound for producing the disclosed heteroaryl-substituted benzothiazole derivative

EFFECT: high efficiency of using the compounds during treatment.

15 cl, 1 tbl, 15 dwg, 82 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to (R)-N-(3-amino-propyl)-N-[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methyl-propyl]-4-methyl-benzamide substantially free from (S)-N-(3-amino-propyl)-N[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-2-methypropyl]-4-methyl-benzamide, or its pharmaceutically acceptable salt which shows the properties of Eg5 inhibitor.

EFFECT: invention also refers to a pharmaceutical composition containing said compound and its pharmaceutically acceptable salt.

4 cl, 27 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

,

where R1 represents CH3; R2 represents halogeno or CN; R3 represents H or CH3; R4 represents H or CH3; n represents 0, 1 or 2; and to their pharmaceutically acceptable salts. Also, the invention refers to a pharmaceutical composition and to application of the compounds of formula (I) in preparing a drug exhibiting antagonist activity in relation to CX3CR1 receptor.

EFFECT: provided the compounds of formula (I) as CX3CR1 receptor antagonists.

20 cl, 1 tbl, 3 dwg, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I) where the bond b represents a double bond; X represents -S-; each Z1 and Z3 independently represents a direct bond, -N(R5) - or - (CH2)q; Z2 represent -C(O)- or -C(S)-; m represents an integer equal to 1; n represents an integer equal to 1; each of q independently represents an integer varying within 1 to 4; R0 represents hydrogen, halogen, hydroxy, unsubstituted C1-C3alkyl or unsubstituted C1-C3alkoxy; R1 is independently selected from a group consisting of halogen, optionally substituted C1-C3alkyl, -R6OR7, -R6N(R7)2, -R6C(O)R7, -R6C(O)OR7, -R6C(O)N(R7)R9N(R7)2, -R6OC(O)R8, -R6C(O)N(R7)2 or -R6OR9N(R7)2; R2 represents hydrogen; R4 is selected from a group consisting of morpholine, isoxazolyl, thiazolyl, oxazolyl, benzisoxazolyl, benzothiazolyl, dioxynyl, dioxolyl, and optionally substituted phenyl. Also, the invention refers to pharmaceutically acceptable salts of the compounds of formula (I) and to a pharmaceutical composition exhibiting antiproliferative activity and containing the compounds of formula (I).

EFFECT: preparing the compounds of formula (I) exhibiting antiproliferative activity.

21 cl, 11 dwg, 5 tbl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 4-(1-aminoethyl)cyclohexylamine derivatives of general formula or pharmaceutically acceptable salts of such a compound, wherein R0 represents H or OH; R1 represents an alkoxy group; U and W represent N, V represents CH and R2 represents H or F, or U and V represent CH, W represents N and R2 represents H or F, or U and V represent N, W represents CH and R2 represents H, or U represents N, V represents CH, W represents CRa and R2 represents H; Ra represents CH2OH or alkoxycarbonyl; A represents the group CH=CH-B or a binuclear heterocyclic system D; B represents a mono- or di-substituted phenyl group wherein the substitutes are halogen atoms; D represents either a group , wherein Z represents CH or N, and Q represents O or S, or a group . The invention also relates to a pharmaceutical composition based on the compound of formula (I) and to use of the compound of formula (I).

EFFECT: novel derivatives having antibacterial activity are obtained.

12 cl, 21 ex

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula (I), its optical isomer or pharmaceutically acceptable salt, R is specified in cl.1 of the patent claim. The compounds may be presented both as an optical isomer, and as a racemic substance, and may be used for mental disorders, such as schizophrenia.

EFFECT: higher efficacy of using the compounds.

8 cl, 4 tbl, 3 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new substituted heteroaryl derivatives of general formula I: , wherein: A means N, CR7-10, with A at the most twice meaning N; W means O, S or NR4, the values B, C, R7-10 are presented in clause 1 of the patent claim. The method for preparing the compound I is described.

EFFECT: compounds show analgesic activity that enables using them for a variety of diseases, especially acute pain, neuropathic, chronic or inflammatory pain.

16 cl, 2 tbl, 307 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are produced new diazepane substituted compounds representing various heterocyclic systems, including condensed, pharmaceutical compositions containing said compounds.

EFFECT: producing the compounds and compositions for preventing and treating neurological and mental disorders and diseases with involved orexin receptors.

13 cl, 1 tbl

New compounds // 2458920

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or to its pharmaceutically acceptable salts wherein -A-(R1)a means a group; -B-(R2)b means a group specified in the patent claim 1, R3 means hydrogen; X means CH2 or O; and Y means CH2. Also, the invention refers to a pharmaceutical composition exhibiting FGFR inhibitor activity on the basis of the declared compound.

EFFECT: there are produced new compounds and based pharmaceutical composition which can find application in medicine for preparing a cancer drug.

8 cl, 1 tbl, 180 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to to new compounds of formula (1) or their pharmaceutically acceptable salts, optionally in the form of (1S)-isomers showing the properties of polo-like kinase (serine-threonine kinase) PLK1 inhibitor. In the compounds of formula (1) , R1 represents a halogen atom; a lower alkyl group having 1-2 carbon atoms, which can be substituted by 3 fluorine atoms; or a cyclopropyl group; R2 represents a hydrogen atom; one of R3 and R4 represents a hydrogen atom while the other one of R3 and R4 represents: a) a lower alkyl group substituted by NRaRb wherein each Ra and Rb, which can be identical or different, represent a lower alkyl group, or each Ra and Rb, which can be different, represent a hydrogen atom, a lower alkyl group or a cycloalkyl group having 3-6 carbon atoms wherein a cycloalkyl group can be substituted by one ore more substitutes which can be identical or different and specified in a group 1): a lower alkyl; b) a 4-6-member aliphatic heterocyclic group specified in an azetidinyl group, a pyrrolidinyl group and a piperidinyl group; c) a lower alkyl group substituted by a 4-6-member aliphatic heterocyclic group specified in an azetidinyl group, a pyrrolidinyl group and a piperidinyl group; d) a 6-member aromatic heterocyclic group specified in a pyridyl group wherein each of an aliphatic heterocyclic group and an aromatic heterocyclic group can be substituted by substitutes specified in a group 1) described above; R5 represents a hydrogen atom, a cyano group, a halogen atom or a lower alkyl group.

EFFECT: compounds can find application in treating oncological diseases.

10 cl, 4 dwg, 8 tbl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new 1H-pyrrolo[3,4-b]quinoline-3,9(2H, 4H)-dione derivatives of general formula 1

wherein R1=Alk, Ar; R2=H, Alk, halogen; R3=H, Alk, halogen; R4=H, Alk, halogen; R5=H, Alk, halogen; R6=CH2Ar, R7=Ar, Also, the invention refers to a method for preparing them.

EFFECT: there are prepared new 1H-pyrrolo[3,4-b]quinoline-3,9(2H, 4H)-dione derivatives possessing anti-tuberculosis activity.

3 cl, 1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I , and pharmaceutically acceptable salts thereof, where L denotes O, S, or CH2; Y denotes N or CH; Z denotes CR3; G denotes CH; R1 denotes a heteroaryl ring of formula , where D1 denotes S, O; D2 denotes N or CR12; D3 denotes CR12; R2 denotes (C6-C10)-aryl; 5-9-member mono- or bicyclic heteroaryl with 1 or 2 heteroatoms independently selected from N or S; a saturated or partially saturated (C3-C7)-cycloalkyl; or a saturated 5-6-member heteocyclyl with 1 heteroatom selected from N, where said aryl, heteroaryl, cycloalkyl and heterocyclyl are optionally substituted with one or two groups independently selected from (C1-C6)-alkyl, F, Cl, Br, CF3, CN, NO2, OR6, C(-O)R6, C(=O)OR6, C(=O)NR6R7, saturated 6-member heterocyclyl with 2 heteroatoms independently selected from N or O, and S(O)2R6, and where said alkyl is optionally substituted with one -OR8 group; R3 denotes H; (C1-C6)-alkyl; (C2-C6)-alkenyl; Cl; Br; OR6; SR6; phenyl; or a 6-member heteroaryl with 1 heteroatom selected from N, where said alkyl and alkenyl are optionally substituted with one group selected from C(=O)OR8, -OR8, -NR8R9; or a saturated 6-member heterocyclyl with 1 heteroatom selected from N or O.

EFFECT: disclosed compounds are used in treating and preventing diseases mediated by insufficient level of glucokinase activity, such as sugar diabetes.

16 cl, 479 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new benzimidazole derivatives of general formula (I) or to its pharmacologically acceptable salts wherein R1 represents a C6-aryl group which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), or a heterocyclic group which represents pyridyl, dihydrobenzofuranyl, 1,3-benzodioxolyl, tetrahydropyranyl, tetrahydrofuranyl which can be substituted by 1-3 groups optionally specified in a group of substitutes (a), R2 represents a C1-C6 alkyl group, R3 represents a C6-aryl group which can be substituted by 1-2 groups optionally specified in a group of substitutes (a), Q represents a group represented by formula =CH-, or a nitrogen atom and a group of substitutes (a) represents a group consisting of a halogen atom, a C1-C6 alkyl group, a C1-C6 halogenated alkyl group, a carboxyl group, a C2-C7 alkylcarbonyl group, a C2-C7 alkoxycarbonyl group, a C1-C6 alkoxy group, a C1-C6 halogenated alkoxy group, an amino group, a 4-morpholinyl group and a di-C1-C6 alkyl)amino group. Also, the invention refers to a pharmaceutical composition based on a compound of formula (I), to a PPARγ activator/modulator based on the compound of formula (I), to using the compound of formula (I), to a method of reducing blood glucose, to a method of activating PPARγ, a method of treating and/or preventing said pathological conditions.

EFFECT: there are produced new benzimidazole derivatives showing PPARγ modulatory activity.

41 cl, 2 dwg, 6 tbl, 76 ex

FIELD: chemistry.

SUBSTANCE: described are novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side with considerable absorption in the region up to 410-420 nm, having general formulae (a)-(k) (structural formula and values of radicals are given in the description), composition which is stabilised with respect to UV radiation and containing novel UV-absorbers, and use of the novel compounds as UV light stabilisers for organic materials.

EFFECT: obtaining novel benzotriazole UV-absorbers, having absorption spectrum shifted towards the long-wave side.

13 cl, 23 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and pharmaceutical industry, namely a combination of clopidogrel and ethylmethylhydroxypyridine. A composition on the basis of the combination is presented in the form of a solid pharmaceutical composition, namely in the form of capsules.

EFFECT: composition of clopidogrel and ethylmethylhydroxypyridine is promising for prevention and treatment of obesity, pathological cardiovascular conditions prevention of ischemic disorders with manifested atherosclerosis, suffered infarction, ischemic stroke, peripheral arterial disease.

2 cl, 2 tbl

Up!