Phosphoinositide-3-kinase inhibitors and pharmaceutical compositions containing said inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae and including their stereoisomers, as well as pharmaceutically acceptable salt, where X denotes O or S; R1 is selected from H, F, CI, Br, I, CN, -CR14R15-NR16R17, -CR14R15-NHR10, -(CR14R15)NR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10)R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NHR12, -NR12C(=Y)R10, -S(O)2R10, -S(O)2NR10R11, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C4 carbocyclyl, piperidinyl, thiopyranyl, phenyl or C5-C6 heteroaryl; R2 is selected from H, C2-C12 alkyl and thiazolyl; R3 denotes a condensed bicyclic heteroaryl selected from indazole, indole, benzoimidazole, pyrrolopyridine, imidazopyridine and quinoline; R10, R11 and R12 independently denote H, C2-C12 alkyl, C3 carbocyclyl, heterocyclyl selected from pyrrolidine, morpholine and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine, benzothiophene; or R10 and R11 together with a nitrogen atom with which they are bonded possibly form a saturated C3-C6 heterocyclic ring, possibly containing one additional ring atom selected from N or O, where said heterocyclic ring is possibly substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10, C(=O)R10, NR12S(O)R11, C(=Y)NR10R11, C1-C12 alkyl and heterocyclyl selected from pyrrolidine; R14 and R15 are independently selected from H or C1-C12 alkyl; R16 and R17 independently denote H or phenyl; R18 and R19 together with a carbon atom with which they are bonded form a C3-C20 heterocyclic ring, where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted with one or more groups independently selected from F, CI, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11, possibly substituted with carbocyclyl, selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted with alkyl and alkylsulphonyl, pyrrolidine, morpholine, piperdine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole; Y denotes O; m equals 0, 1 or 2; n equals 1 and t equals 2. The invention also relates to a pharmaceutical composition which modulates lipid kinase activity, based on said compounds.

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used to treat lipid kinase-mediated diseases, for example, cancer.

48 cl, 2 tbl, 372 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from formula Ia and formula Ib:

and stereoisomers, their pharmaceutically acceptable salt,
where X represents O or S;
R1selected from H, F, Cl, Br, I, CN, -CR14R15-NR16R17, -CR14R15-Other10, -(CR14R15)tNR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11-The other12, -NR12C(=Y)R11, -S(O)2R10, -S(O)2NR10R11C2-C12of alkyl, C2-C8alkenyl, C2-C8the quinil,3-C4carbocycle, piperidinyl, topira the sludge, phenyl or C5-C6heteroaryl;
R2selected from H, C1-C12the alkyl and thiazolyl;
R3represents a condensed bicyclic heteroaryl selected from indazole, indole, benzimidazole, pyrrolopyridine, imidazopyridine and quinoline;
R10, R11and R12are independently H, C1-C12alkyl, C3carbocyclic, heterocyclic selected from pyrrolidine, research and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine of benzothiophene; or
R10and R11together with the nitrogen to which they are attached may form a saturated3-C6heterocyclic ring, possibly containing one additional ring atom selected from N or O, where the aforementioned heterocyclic ring possibly substituted by one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10C(=O)R10, NR12S(O)2R11C(=Y)NR10R11C1-C12the alkyl and heterocyclyl selected from pyrrolidine;
R14and R15independently selected from N or C1-C12of alkyl;
R16and R17are independently H or phenyl;
R18and R19together with the carbon to which they are attached, form a3-C20heterocycle the mini-ring,
where these alkyl, alkenyl, quinil, carbocyclic, heterocyclic, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted by one or more groups independently selected from F, Cl, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11possibly substituted carbocycle selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted by alkyl and alkylsulfonyl, pyrrolidine, research, piperidine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole;
Y represents O;
m denotes 0, 1 or 2;
n denotes 1, and
t denotes 2.

2. The compound according to claim 1 of formula Ia, where X represents S, which has the formula:

3. The compound according to claim 1 of formula Ib, where X represents S, which has the formula:

4. The compound according to claim 1 of formula Ia, where X represents O, which has the formula:

5. The compound according to claim 1, where R1not only is em a N.

6. The compound according to claim 1, where R1represents -(CR14R15)tNR10R11where t denotes 2, and R10and R11together with the nitrogen to which they are attached, form a3-C6heterocyclic ring.

7. The compound according to claim 1, where R1represents -(CR14R15)nNR12S(O)2R10where n is 1; R12, R14and R15independently selected from H and C1-C12the alkyl and R10represents a C1-C12alkyl or phenyl.

8. The compound according to claim 1, where R1represents -(CR14R15)mOR10where n denotes 1, and R10, R14and R15independently selected from H and C1-C12the alkyl.

9. The compound according to claim 1, where R1represents -(CR14R15)nS(O)2R10where n denotes 1, and R14and R15represent N.

10. The connection according to claim 9, where R10represents a C1-C12alkyl or phenyl.

11. The compound according to claim 1, where R1represents -(CR14R15)nS(O)2NR10R11where n denotes 1, and R14and R15represent N.

12. The compound according to claim 1, where R1represents-C(=Y)NR10R11where Y is Oh, and R10and R11together with the nitrogen to which they are connec the us, form3-C6heterocyclic ring.

13. The connection section 12, where R10and R11together with the nitrogen to which they are attached, form a heterocyclic ring selected from morpholinyl, piperidinyl, piperazinil and pyrrolidinyl.

14. The compound according to claim 1, where R1represents-C(=Y)NR10R11where Y is Oh, and R10and R11independently selected from H and C1-C12the alkyl.

15. The compound according to claim 1, where R1represents-C(=Y)NR10R11where Y is Oh, and R10and R11independently selected from H and phenyl.

16. The compound according to claim 1, where R1is an-other12where R12represents phenyl, 2-pyridinyl or 3-pyridinyl.

17. The compound according to claim 1, where R1represents-NR12C(=Y)R11where Y represents Oh, R12represents N or C1-C12alkyl, and R11represents a C1-C12alkyl, C3carbocyclic or phenyl.

18. The connection 17, where R11selected from methyl, ethyl, isopropyl and 2,2-dimethylpropyl.

19. The connection 17, where R11is cyclopropyl.

20. The compound according to claim 1, where R1represents S(O)2NR10R11where R10and R11together with the nitrogen to which they are attached, form a CGU is eroticlinks ring, selected from piperidinyl, piperazinil and pyrrolidinyl.

21. The compound according to claim 1, where R1represents S(O)2NR10R11where R10and R11independently selected from H and C1-C12the alkyl.

22. Connection item 21, where R10and R11independently selected from H, substituted ethyl and substituted propyl.

23. The compound according to claim 1, where R1represents a C2-C12alkyl.

24. The compound according to claim 1, where R1represents a C2-C8alkenyl.

25. The compound according to claim 1, where R1represents a C2-C8quinil.

26. Connection A.25, where C2-C8quinil substituted C5-C6heterocyclyl.

27. Connection p, where C5-C6heterocyclyl selected from morpholinyl, piperazinil and pyrrolidinyl.

28. Connection item 27, where R1selected from the group:
and

29. The compound according to claim 1, where R1represents a possibly substituted phenyl.

30. The connection clause 29, where phenyl is substituted by one or more groups selected from N-methylcarbamate, isopropylbenzylamine, methylsulfonyl, 2-hydroxy-2-methylpropanamide, 2-hydroxypropanoic, 2-methoxyacetate, (propane-2-ol)sulfonyl, 2-amino-2-methylpropanamide, 2-aminoacetyl, 2-hydroc is acetamido, methylsulfonylamino, 2-(dimethylamino)ndimethylacetamide, amino, acetylamino, carboxamide, (4-methylpiperazine)-1-methyl, hydroxymethyl and methoxy.

31. The compound according to claim 1, where R1represents a C3-C4carbocyclic.

32. The compound according to claim 1, where R1is piperidinyl or thiopyran.

33. The compound according to claim 1, where R1represents a C5-C6heteroaryl.

34. Connection p, where R1represents 3-pyridyl, 4-pyridyl or 5-pyrimidinyl.

35. The compound according to claim 1, where R2represents N.

36. The compound according to claim 1, where R3selected from


where the wavy line indicates the place of attachment.

37. Connection p, where R3represents 1H-indazol-4-yl.

38. Connection p, where R3represents 1H-indol-4-yl.

39. The compound according to claim 1, selected from the group including:
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylbenzamide;
2-(1H-indazol-4-yl)-4-morpholino-6-(3-isopropylcyclopentadienyl)thieno[3,2-d]pyrimidine;
(S)-1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)ethanol;
(R)-1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]feast midin-6-yl)ethanol;
2-(1H-indazol-4-yl)-4-morpholino-6-(propylsulfonyl)thieno[2,3-d]pyrimidine;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-methoxypropan-2-ol;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-ol;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1,3-dimethoxypropane-2-ol;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-(diethylamino)propan-2-ol;
1-(4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-4-hydroxypiperidine-1-yl)Etalon;
2-(1H-indazol-4-yl)-6-(3-(methylsulphonyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-hydroxy-2-methylpropanamide;
(2S)-N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-hydroxypropane;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methanol;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methanamine;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methane(methylsulphonyl)amine;
2-(1H-indazol-4-yl)-4-morpholino-N-(pyridin-3-yl)thieno[3,2-d]pyrimidine-6-amine;
2-(4-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)ethyl)piperazine-1-yl)-N,N-dimethylacetamide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-2-methoxyacetate;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-methoxyacetate;
2-(1H-indazol-4-yl)-4-morpholino-N-(pyridin-2-yl)thieno[3,2-d]pyrimid the n-6-amine;
(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)(4-methylpiperazin-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)(4-hydroxypiperidine-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)(4-acetylpiperidine-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)(4-methylsulfonylmethane-1-yl)methanon;
2-(1H-indazol-4-yl)-N-isopropyl-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
N-(2,2,2-triptorelin)-2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
N-(2-hydroxyethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
N-ethyl-2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-N,N-dimethyl-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-N-methyl-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-tetrahydro-2H-thiopyran-4-ol;
1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)cyclobutanol;
6-chloro-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
(R)-1-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenylsulfonyl)propan-2-ol;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-amino-2-methylpropanamide;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-aminoacetate;
(S)-1-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3-d]pyrimidine-6-yl)phenylsulfonyl)propan-2-ol;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-hydroxyacetamido;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)propan-2-ol;
2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-carboxylic acid;
2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
6-((3-methoxypropylamine)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(2-(4-methylsulfonylmethane-1-yl)ethyl)thieno[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylpropanamide;
2-(1H-indazol-4-yl)-6-((methylsulphonyl)methyl)-4-morpholinothio[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propanamide;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N,N-dimethylpropanamide;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)-1-(4-methylsulfonylmethane-1-yl)propanone;
2-(1H-indazol-4-yl)-4-morpholino-N-phenylthieno[3,2-d]pyrimidine-6-amine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)benzoylmethylecgonine;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-2-(dimethylamino)ndimethylacetamide;
2-(1H-indazol-4-yl)-6-(3-methoxypyridine-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)pentane-3-ol;
6-(6-herperidin-3-yl)-2-(1H-indazol-4-yl)-4-morpholinothio [3,2-d]pyrimidine;
6-(2-herperidin--yl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(4-methoxypyridine-3-yl)-4-morpholinothio[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)benzolamide;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)benzamide;
N-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)ndimethylacetamide;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)benzamide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propionamide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)ndimethylacetamide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)isobutyramide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)benzamide;
3-(1H-indazol-4-yl)-4-morpholino-6-(2-(4-methylsulfonylmethane-1-yl)propyl)thieno[3,2-d]pyrimidine;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-(methylacetamide)piperidine-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(3-(methylsulphonyl)pyrrolidin-1-yl)methanon;
2-(1H-indazol-4-yl)-N-(2-(methylsulphonyl)ethyl)-4-morpholinothio [3,2-d]pyrimidine-6-carboxamide;
N-ethyl-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-N-methyl-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)cyclopropanecarboxamide;
N-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-3,3-dimethylbutyramide;
2-(2-methyl-1H-benzo[d]imidazol-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(3-(4-methylpiperazin-1-yl)prop-1-inyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(3-(pyrrolidin-1-yl)prop-1-inyl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(3-morpholinopropan-1-inyl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(3-(4-methylsulfonylmethane-1-yl)thieno[3,2-d]pyrimidine;
(2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methanol;
2-(1H-indazol-4-yl)-6-((1-methylpiperidin-4-ilidene)methyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(4-methoxy-1-methylpiperidin-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-methylpiperidin-4-ol;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-sulfanilyl-N-(2-morpholinoethyl)methanamine;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylsulphonyl-N-(2-N,N-dimethylaminoethyl)methanamine;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methyl, N-(3-morpholinepropanesulfonic)methanamine;
(2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methyl, N-(3-morpholinepropanesulfonic)methanamine;
2-(1H-indazol-4-yl)-N-(2-methoxyethyl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indol-4-yl)-N-(2-methoxyethyl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
(2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methyl-N-(2-N,N-dimethylaminomethyl)methanamine;
2-(1H-indol-4-yl)6-(2-(methylsulphonyl)ethyl)-4-morpholinothio [3,2-d]pyrimidine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylacetamide;
N-((2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylacetamide;
N-((2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-(methyl)methylsulfonate;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylsulphonyl-1-methylpyrrolidine-3-amine;
2-(1H-indazol-4-yl)-6-(3-((4-methylsulfonylmethane-1-yl)methyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(3-((4-methylpiperazin-1-yl)methyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine;
4-(4-morpholinothio[3,2-d]pyrimidine-2-yl)indolin-2-he;
2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(pyrimidine-5-yl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-phenylfuro[3,2-d]pyrimidine;
N-(cyclopropylmethoxy)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-4-morpholino-6-(1H-pyrazole-4-yl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-phenylthieno[3,2-d]pyrimidine;
(S)-1-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methylamino)propan-2-ol;
2-(1H-indazol-4-yl)-N-(methylsulphonyl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
6-(sibutraminesolution)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(3-hydroxybenzenesulfonic)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-((4-piperazine-2-he)self the Nile)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(4-methylpiperazine)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(2-hydroxyethylpiperazine)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(3-hydroxymethylimidazole)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(4-hydroxymethylimidazole)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(4-(2-hydroxyethyl)piperidinophenyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(4-(2-hydroxyethyl)piperazinylmethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(4-hydroxypropanesulfonic)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(3-hydroxypyrrolidine)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(2-piperazineethanesulfonic)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(2-N-morpholinepropanesulfonic)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(3-methoxyphenylacetyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(N,N-bis-2-hydroxyethylaminomethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(2-hydroxyethylaminomethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(dimethylaminomethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(methylaminomethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4 morpholinothio[3,2-d]pyrimido the-6-amine;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-ylamino)ethanol;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-sulfanilyl-N-(2-methoxyethyl)methanamine;
1-(4-(4-morpholinothio[3,2-d]pyrimidine-2-yl)indolin-1-yl)Etalon;
2-(1H-indazol-6-yl)-4-morpholinothio[3,2-d]pyrimidine;
4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-(thiazol-2-yl)methyl)piperidine-4-ol;
4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-(methylsulphonyl)piperidine-4-ol;
4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-((pyridin-2-yl)methyl)piperidine-4-ol;
2-(1H-indazol-4-yl)-4-morpholino-6-phenylfuro[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(methylsulphonyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-ol;
2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-(N-phenylsulfonyl)carboxamide;
(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)methanol;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)ndimethylacetamide;
2-(1H-indazol-4-yl)-4-morpholino-6-(pyridin-4-yl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(pyridin-3-yl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(3,4-acid)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(4-acetyl-piperazineethanol)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(4-methylsulphonyl-piperazineethanol is)thieno[3,2-d]pyrimidine;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-(2-hydroxyethyl)piperazine-1-yl)methanon;
N-benzyl-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
N-(3-hydroxyphenyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-4-morpholino-N-phenylthieno[3,2-d]pyrimidine-6-carboxamide;
N-((dimethylcarbamoyl)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-(pyrrolidin-1-yl)piperidine-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(piperazine-2-he)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-hydroxypiperidine-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(morpholino)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(3-(methylamino)pyrrolidin-1-yl)methanon;
N-(2,2,2-triptorelin)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-4-morpholino-N-(2-morpholinoethyl)thieno[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-N-isobutyl-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-4-morpholino-N-(2-(piperidine-1-yl)ethyl)thieno[3,2-d]pyrimidine-6-carboxamide;
N,N-bis(2-hydroxyethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)ethanol;
N(1-hydroxypropan-2-yl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-methylpiperazin-1-yl)methanon;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-methylsulfonylmethane-1-yl)methanon;
2-(1H-indazol-4-yl)-N,N-dimethyl-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-6-(4-(methylsulphonyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(3-(methylsulphonyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine;
N-(2-hydroxyethyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-acetylpiperidine-1-yl)methanon;
(4-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)methanol;
1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-2-methylpropan-2-ol;
2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indol-5-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indol-6-yl)-4-morpholinothio[3,2-d]pyrimidine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-(methyl)methylsulfonate;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)ndimethylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)benzamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d pyrimidine-6-yl)methyl)picolinate;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)nicotinamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)sonico inamed;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-1-(4-methylpiperazin-1-yl)propane-1-he;
2-(1H-indazol-4-yl)-6-(methoxymethyl)-4-morpholinothio[3,2-d]pyrimidine;
6-((benzyloxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(((pyridine-2-yl)methoxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(((pyridine-3-yl)methoxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(((pyridine-4-yl)methoxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine; and
2-(1H-indazol-4-yl)-4-morpholino-6-(phenoxymethyl)thieno[3,2-d]pyrimidine.

40. The compound according to claim 1, selected from the group including:
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)benzamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)picolinate;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)nicotinamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)ndimethylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)isonicotinamide;
2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-N-methylsulfonylmethane-1-yl)methanon;
2-(1H-indazol-4-yl)-N-methyl-4-morpholinothio[3,2-d]pyrimidine-6-carboxamide;
(S)-1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)ethanol;
(R)-1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)et is Nol;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methanol;
2-(1H-indazol-4-yl)-6-(4-methoxypyridine-3-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-carboxamide;
2-(1H-indazol-4-yl)-4-morpholino-6-(3-(morpholinomethyl)phenyl)thieno[3,2-d]pyrimidine;
methyl 3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-5-aminobenzoate;
N-(3-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methylamino)phenyl)ndimethylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)benzolamide;
3-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methylamino)benzamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N,N-dimethylethanamine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)morpholine-4-carboxamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)]N-vinylsulfonylacetamido;
3-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-1,1-dimethyloctane;
1-(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)ethanol;
2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)sulfonamide;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-amine;
3-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)oxazolidin-2-he;
6-((1H-imidazol-1-yl)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-((1H-1,2,4-triazole-1-yl)methyl)-2-(1H-indazol-4-yl)-4-mo is polination[3,2-d]pyrimidine;
2-(N-indazol-4-yl)-6-(methoxymethyl)-4-morpholinothio[3,2-d]pyrimidine;
6-((benzyloxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholino-6-(phenoxymethyl)thieno[3,2-d]pyrimidine;
6-(((pyridine-2-yl)methoxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
4 morpholino-2-(1H-pyrrolo[2,3-d]pyridin-5-yl)-7-(thiazol-5-yl)thieno[3,2-d]pyrimidine;
6-(((pyridine-3-yl)methoxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
6-(((pyridine-4-yl)methoxy)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(2-(1H-indol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-ol;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-hydroxy-2-methylpropanamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-hydroxyacetamido;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-3-(methyl sulfonyl)benzamide;
6-((1H-pyrazole-1-yl)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
1-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-1H-benzo[d]imidazol-2(3H)-he;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylsulfonylbenzoyl;
2-(1H-indazol-4-yl)-6-(isoxazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-ethylbenzamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-(N-methylsulfonylamino is)ndimethylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-aminoacetate;
2-(1H-indazol-4-yl)-4-morpholino-6-(1-(4-N-methylsulfonylmethane-1-yl)ethyl)thieno[3,2-d]pyrimidine;
2-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methoxy)-N,N-dimethylacetamide;
2-(1H-indazol-4-yl)-6-((E)-3-methoxypropan-1-enyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(3-methoxyphenyl)-4-morpholinothio[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-((S)-2-hydroxypropyl)benzamide;
(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)(morpholino)methanon;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)benzoic acid;
(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)(4-methylpiperazin-1-yl)methanon;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-(2-(dimethylamino)ethyl)benzamide;
N-(3-(2-(lH-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)ndimethylacetamide;
5-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-((S)-2-hydroxypropyl)pyridine-3-carboxamide;
5-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-(2-(dimethylamino)ethyl)pyridine-3-carboxamide;
5-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylpyridin-3-carboxamide;
2-(2-(1H-indol-6-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-ol;
2-(4-morpholino-2-(quinoline-3-yl)thieno[3,2-d]pyrimidine-6-yl)propan-2-ol;
(5-(2-(1H-in the azole-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)pyridine-3-yl)(morpholino)methanon;
(5-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)pyridine-3-yl)(4-methylpiperazin-1-yl)methanon;
5-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)pyridine-3-carboxylic acid;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-(dimethylamino)ndimethylacetamide;
2-(4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)propan-2-ol;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)-N-methylacetamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-N-methylsulfonylmethane-4-yl)methanol;
1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)ethanol;
2-(1H-indazol-4-yl)-4-morpholino-6-((pyridine-3-yloxy)methyl)thieno[3,2-d]pyrimidine;
7-methyl-6-(5-(methylsulphonyl)pyridine-3-yl)-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
6-((hexahydro-2-methylsulfonylbenzoyl[3,4-C]pyrrol-5(1H)-yl)methyl)-2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine;
3-(2-(1H-indazol-4-yl)-7-methyl-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylbenzamide;
N-(3-(2-(1H-indazol-4-yl)-7-methyl-4-morpholinothio[3,2-d]pyrimidine-6-yl)phenyl)ndimethylacetamide;
2-(1H-indazol-4-yl)-7-methyl-6-(3-(methyl sulfonyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(4-methoxypyridine-3-yl)-7-methyl-4-morpholinothio[3,2-d]pyrimidine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-3-methoxybenzamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio is but[3,2-d]pyrimidine-6-yl)methyl)-4-methoxybenzamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-4-methoxybenzylamine;
2-(1H-indazol-4-yl)-6-((2-methyl-1H-imidazol-1-yl)methyl)-4-morpholinothio[3,2-d]pyrimidine;
N((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-methoxybenzylamine;
3-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methylamino)-N-methylbenzamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-6-methoxypyridine-3-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)pyridine-3-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-4-morpholinomethyl;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-1H-pyrazole-5-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-1,3-dihydrobenzo[C]thiophene-1,1-dioxide-5-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-6-morpholinopropan-3-amine;
N1-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-3-methylsulfonylamino-1-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio [3,2-d]pyrimidine-6-yl)methyl)-3-(methylsulphonyl)benzolamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-cyclopropylacetylene;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-(3-methoxyphenyl)ndimethylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-(4-methoxyphenyl)ndimethylacetamide;
(2-(1H-shall indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylsulfonylmethane;
2-(N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N,N-bis-(N-temporoparietal)-methanamine;
2-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methylamino)-N-cyclopropylacetic;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-(methylsulphonyl)ethanamine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-3-(methylsulphonyl)propan-1-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-3-(dimethylaminomethyl)propan-1-amine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methyl(phenyl)methanamine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)(3-methoxyphenyl)-N-methylmethanamine;
N-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-yl)benzamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylmethanamine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylbenzamide;
N-((2-(1H-indazol-4-yl)-7-methyl-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylsulphonyl-methanamine;
N-((2-(1H-indol-5-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylacetamide;
N-(3-(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)phenyl)ndimethylacetamide;
2-(1H-indazol-4-yl)-6-(3-(methylsulphonyl)phenyl)-4-morpholinothio[2,3-d]pyrimidine;
7-methyl-6-(3-(methylsulphonyl)phenyl)-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
2-(1 ሺ-indazol-4-yl)-6-(4-methoxypyridine-3-yl)-4-morpholinothio[2,3-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(1H-indol-4-yl)-4-morpholinothio[3,2-d] pyrimidine;
2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)-N-methylsulfinylpropyl-2-amine;
N-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-yl)ndimethylacetamide;
2-(1H-indazol-4-yl)-4-morpholino-6-(6-morpholinopropan-3-yl)thieno[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-6-(2-(4-N-methylsulfonylmethane-1-yl)propan-2-yl)-4-morpholinothio[3,2-d]pyrimidine;
2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-carbonitrile;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-methoxy-N-methylacetamide;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-(methylthio)phenyl)methanol;
(2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)-N-methylsulphonyl, N-methylmethanamine;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)methyl)-N-methylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-hydroxy-N,2-dimethylpropanamide;
N-((2-(1H-indazol-4-yl)-7-methyl-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-N-methylacetamide;
N-((2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)methyl)-2-hydroxy-N-methylacetamide;
N-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-yl)nicotinamide;
N-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-yl)-3-methoxybenzamide;
N-(2-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-yl)-4-methods SibEnzyme;
(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)(4-(methylsulphonyl)phenyl)methanol;
2-(2-(2-methyl-3H-imidazo[4,5-b]pyridine-6-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)propan-2-ol;
(S)-1-(3-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)phenylsulfonyl)propan-2-ol;
7-methyl-6-(3-(N-morpholino)sulfonyl)phenyl)-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
N-methyl,N-methylsulphonyl(4 morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)methanamine;
6-(3-(methylsulphonyl)phenyl)-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
4 morpholino-6-phenyl-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
7-methyl-4-morpholino-6-phenyl-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
(2S)-2-hydroxy-N-((3-(7-methyl-4-morpholino-2-(1H-pyrrolo [2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)phenyl)methyl)propanamide;
2-(4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)propan-2-ol;
7-methyl-6-(3-(2-hydroxyethylaminomethyl)phenyl)-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
N-methylsulphonyl(3-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)phenyl)methanamine;
(4-hydroxypiperidine-1-yl)(3-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)phenyl)methanon;
N-(2-hydroxyethyl)-3-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]PI is kidin-6-yl)benzamide;
(3-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)phenyl)(4-methylpiperazin-1-yl)methanon;
4 morpholino-6-(6-morpholinopropan-3-yl)-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine;
4-(4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)thiazol-2-amine;
6-(7-methyl-6-(3-(methylsulphonyl)phenyl)-4-morpholinothio[3,2-d] pyrimidine-2-yl)-3H-imidazo[4,5-b]pyridine;
2-(2-(1H-imidazo[4,5-b]pyridine-6-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-ol;
2-methyl-6-(7-methyl-6-(3-(methylsulphonyl)phenyl)-4-morpholinothio[3,2-d]pyrimidine-2-yl)-3H-imidazo[4,5-b]pyridine;
2-(2-(2-methyl-3H-imidazo[4,5-b]pyridine-6-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)propan-2-ol;
5-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)-N-(2-morpholinoethyl)pyridine-2-amine;
3-(5-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)pyridine-2-ylamino)propane-1,2-diol;
2-(2-(5-(7-methyl-4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)pyridine-2-ylamino)ethoxy)ethanol;
N-methyl(4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[3,2-d]pyrimidine-6-yl)methanamine;
1-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)pyrrolidin-2-he;
3-(2-(1H-indazol-4-yl)-4-morpholinothio[3,2-d]pyrimidine-6-yl)oxazolidin-2-he;
2-(4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)propan-2-ol;
(4-methylpiperazin-1-yl)(3-(4-morpholino-2-(1H-feast of the olo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)phenyl)methanon;
2-(2-(2-methyl-3H-imidazo[4,5-b]pyridine-6-yl)-4-morpholinothio[2,3-d]pyrimidine-6-yl)propan-2-ol;
N-(3-(4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)benzyl)methanesulfonamide;
N-(2-(dimethylamino)ethyl)-N-((4-morpholino-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-6-yl)methyl)methanesulfonamide;
2-(4-morpholino-2-(quinoline-3-yl)thieno[2,3-d]pyrimidine-6-yl)propan-2-ol; and
4-(6-(3-(methylsulphonyl)phenyl)-2-(1H-pyrrolo[2,3-b]pyridine-5-yl)thieno[2,3-d]pyrimidine-4-yl)morpholine.

41. Pharmaceutical composition for modulation of libidinous activity containing a compound according to claim 1 and a pharmaceutically acceptable carrier.

42. Composition for modulation of libidinous activity containing a compound according to claim 1 in quantity for the detectable inhibition of PI3 kinase activity and a pharmaceutically acceptable carrier, adjuvant or excipient.

43. Method of preparation of a pharmaceutical composition for modulation of libidinous activity, which combine the compound according to claim 1 with a pharmaceutically acceptable carrier.

44. Method of inhibiting or modulating activity of lipid kinases, in which the lipid kinase is brought into contact with an effective inhibiting amount of a compound according to claim 1.

45. The method according to item 44, where the lipid kinase is a PI3K.

46. The method according to item 45, where PI3K p110 is alpha subunit.

4. Method of inhibiting or modulating activity of lipid kinases in a mammal, in which this mammal is administered a therapeutically effective amount of a compound according to claim 1.

48. The method according to p, where the lipid kinase is a PI3K.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula where R1 is selected from H, F, CI, Br, CF3, C1-C6 alkoxy and OH; R2 is selected from H and C1-C6 alkyl; n equals 1-5; m equals 0 or 1; and Y is selected from CH2, NR3, (NR3R4)+X-, O and S; R3 and R4 are independently selected from H and C1-C4 alkyl; and X- is selected from pharmaceutically acceptable anions. The invention also relates to a method of producing said compound and to an antiviral pharmaceutical composition based on said compound of formula (I).

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used in medicine to treat a viral diseases such as herpes.

19 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: described is a compound of general formula: [1], where R1 denotes an optionally substituted C2-C12 alkyl, aryl or heterocyclic group which can be a mono- or bicyclic 5-11-member radical, where the heteroatoms can be nitrogen, oxygen or sulphur; X1 denotes C2-C4 an alkylene group; X2 denotes a bond; X3 denotes a group of general formula NR3 or CR4R5NR3 (where R3 denotes a hydrogen atom, optionally substituted lower alkyl group or imino-protective group) and R4 and R5 are identical or different, and each denotes a hydrogen atom or a lower alkyl group or bond; X4 denotes a lower alkylene or lower alkenylene or lower alkynylene group, which can be substituted with one or more oxo groups or a bond; X5 denotes a sulphur atom or bond; Y1 denotes an optionally substituted divalent 4-, 5- or 6-member alicyclic hydrocarbon residue or an optionally subsituted divalent 5- or 6-member alicyclic amine residue, where the heteroatoms can be nitrogen or oxygen; Z1, Z2, Z3, Z4, Z5 and Z6 are identical or different, and each denotes a nitrogen atom or a group of general formula CR7 (where R7 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted amino group, or an amino group substituted with one or more C1-6 alkyl groups, a lower alkyl group, a cycloalkyl, a lower alkoxy group or a monocyclic 5-member heterocyclic group which can be substituted with one or more halogen atoms, where the heteroatoms can be nitrogen, acid or sulphur or a group of general formula Q1CO2R10 (where R10 denotes a carboxyl-protective group and Q1 denotes a lower alkenylene group), provided that at least one of Z3, Z4, Z5 and Z6 denotes a nitrogen atom, or salt thereof. The invention also describes an antimicrobial agent based on said compound.

EFFECT: novel compounds which can be used as antimicrobial agents are obtained and described.

25 cl, 176 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel crystalline form of vinflunine ditartrate, production method thereof and use thereof in therapy, especially for cancer pathology treatment.

EFFECT: high stability and wide variety of galenic forms.

8 cl, 3 ex, 5 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a compound presented by formula (1), to its salt or hydrate where in formula R1 represents a methylene group, R2 represents a phenyl group which can contain a substitute(s), or a heterocyclic group which can contain a substitute(s), the cycle A represents a 6- or 7-members cycle (where cycle-making atoms of the cycle A different from a sulfur atom in position 6 are carbon atoms), and R3 represents a hydrogen atom, or 1-3 equal or different substitutes used to substitute the cycle A where the possible substitutes are specified in clause 1 of the patent claim. Also, the invention refers to a pharmaceutical composition exhibiting an anticancer activity, on the basis of the compound presented by formula (1).

EFFECT: there are produced new compounds and pharmaceutical composition on their basis which can find application in medicine for cancer treatment.

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds (la) of formula applied as tyrosine kinase c-Met inhibitors. , where: LA is selected from ,

or ; RA is selected from:

or each RA2 and RA6 represents hydrogen; RA3 represents RAr; or RA3, RA4 and carbon atoms whereto attached form 6-members aryl, optionally substituted, in the amount up to 4 by independent groups RAr, or a 5-6-members heterocyclyl or heteroaryl ring containing at least one O, N or S atom; R represents -OH; RA5 represents hydrogen or RAr; LB represents a covalent bond or -N(R*)-; RB represents halogen, NH2 or C1-8aliphatic group, optionally substituted by R; a 6-10-members aryl ring; a 3-7-members carbocyclyl ring, a 5-10-members heteroaryl ring containing 1-4 heteroatoms independently selected from nitrogen, oxygen and sulphur atoms, where each said aryl or heteroaryl ring is optionally substituted, in the amount up to five by independent groups RAr; R represents halogen, -R°, -SR°, Ph, optionally substituted R° or -C(O)OR°; each RAr is independently selected from halogen, -R°, -OR°, -SR°, Ph, optionally substituted in the amount up to five by independent groups -R°, -CN, -N(R°)2 or -C(O)OR°; or two adjacent groups RAr taken together, represent 1,2-methylenedixy or 1,2-ethylenedixy; each R* represents hydrogen; and each R° represents independently hydrogen, an optionally substituted C1-6aliphatic radical or an unsubstituted 5-6-members heteroaryl or heterocyclic ring containing 1-3 heteroatoms independently selected from nitrogen, oxygen and sulphur atoms.

EFFECT: invention refers to pharmaceutically acceptable compositions containing the compounds under the invention, and methods of application of the compositions in treatment of various proliferative disorders.

10 cl, 4 tbl, 548 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I in which A denotes X denotes O; R denotes H; R1 denotes OH, CN, a nitro group, NH2, NR2CSR8, NR2CONR2R9, NR2C SNR2R9, NR2SO2R10, NR2CONR6R7, NR2CSNR6R7, NR2R9, SO2R10, SOR10, alkyl containing 1-4 carbon atoms, fluorinated alkyl containing 1-4 carbon atoms, alkenyl containing 2-6 carbon atoms, alkynyl containing 2-6 carbon atoms, where each alkyl, fluorinated alkyl, alkenyl or alkynyl group in each case is unsubstituted or substituted with Ar or He, cycloalkenyl containing 5-8 carbon atoms, alkoxy group containing 1-4 carbon atoms, cycloalkoxy group containing 3-7 carbon atoms, cycloalkylalkoxy group containing 4-7 carbon atoms, fluorinated alkoxy group containing 1-4 carbon atoms, fluorinated hydroxyalkyl containing 1-4 carbon atoms, hydroxyalkoxy group containing 2-4 carbon atoms, an ordinary hydroxyalkoxy group containing 2-4 carbon atoms, monoalkylamino group containing 1-4 carbon atoms, dialkylamine group, where each alkyl group independently contains 1-4 carbon atoms, alkoxycarbonyl containing 2-6 carbon atoms, Het or OAr; R2 denotes H, alkyl containing 1-4 carbon atom, cycloalkyl containing 3-7 carbon atoms, and cycloalkyl alkyl containing 4-7 carbon atoms; R6 and R7 independently denote H, alkyl containing 1-4 carbon atoms, cycloalkyl containing 3-7 carbon atoms, or cycloalkylalkyl containing 4-7 carbon atoms, or R6 and R7 together denote an alkylene group containing 4-6 carbon atoms, which forms a ring with an N atom; R8 denotes alkyl containing 1-4 carbon atoms, fluorinated alkyl containing 1-4 carbon atoms, alkenyl containing 3-6 carbon atoms, alkynyl containing 3-6 carbon atoms, where each alkyl, fluorinated alkyl, alkenyl or alkynyl group is unsubstituted or substituted with Ar, cycloalkyl containing 3-7 carbon atoms, or Het; R9 denotes Ar or Het; R10 denotes alkyl containing 1-4 carbon atoms which is unsubstituted or substituted with Ar, or NR6R7; Ar denotes an aryl group containing 6-10 carbon atoms, which is unsubstituted or substituted once or several times with an alkyl containing 1-8 carbon atoms, alkoxy group containing 1-8 carbon atoms, halogen, cyano group or combinations thereof; and Het denotes dihydropyranyl, tetrahydropyranyl, tetrahydrofuranyl, tetrahydrothienyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, isoxazolinyl, thiazolyl, oxazolyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrimidinyl, indolyl, quinolinyl, isoquinolinyl or naphthyridinyl, which is unsubstituted or substituted once or several times with halogen, aryl containing 6-10 carbon atoms, which is optionally substituted with alkyl containing 1-8 carbon atoms, alkoxy group containing 1-8 carbon atoms, oxo group, -CXR11 or combinations thereof, or R11 denotes alkyl containing 1-4 carbon atoms which is unsubstituted or substituted with Ar or Het; or pharmaceutically acceptable salts thereof, where formula IA is attached to the rest of the bonding molecule in the 3, 4 or 7 positions. The invention also relates to a pharmaceutical composition and to use of compounds in any of claims 1-37.

EFFECT: obtaining novel biologically active compounds, having nicotinic acetylcholine receptor subtype α7 ligand activity.

59 cl, 316 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula IB , where radicals R1-R5 have values, given in invention formula. In range of claimed invention also described are pharmaceutical compositions, which include compounds of IB formula, and methods of application of such compounds and compositions for treatment of different malfunctions, mainly selected from immune response reactions.

EFFECT: compounds by claimed invention have inhibiting action with respect to proteinkinases and, in particular with respect to JAK-3, ROCK or Aurora kinases.

55 cl, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to 6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives of general formula , where R is an optional ortho- or meta-substitute selected from halogen and (C1-4)alkyloxy; R1 is halogen or CF3; R2 is H, (C1-4)alkyloxy or halogen; R3 is H or (CH2)n-NR5R6; R4 is H or (C1-6)alkyl, optionally substituted COOR7 or NR8R9; R5 and R6 independently denote H, (C3-8)cycloalkyl, quinuclidin-3-yl, (C2-6)alkenyl or (C1-6)alkyl, optionally substituted mono-substituted with CF3, (C3-8)cycloalkyl, (C6)aryl, a 5- or 6-member heteroaryl group, OH, (C1-6)alkyloxy, (C6-10)aryloxy, CONR11R12, NR13R14 or NR13SO2(C1-4)alkyl; or R5 and R6 together with a nitrogen atom to which they are bonded form a 4-8-member saturated heterocyclic ring which also contains 1 heteroatom selected from O, SO2 and NR15, where the ring is optionally mono-substituted or di-substituted with oxo, (C1-4)alkyl, (C3-8)cycloalkyl, NR16R17 or CONR18R19; R7 is H or (C1-4)alkyl; R8 and R9 independently denote H, (C1-4)alkyl (optionally substituted di(C1-4)alkylamino) or (C3-8)cycloalkyl; or R8 and R9 together with a nitrogen atom with which they are bonded form a 4-8-member saturated heterocyclic ring which also contains one heteroatom which is O; R11 and R12 independently denote H or (C1-4)alkyl; R13 and R14 independently denote H or (C1-4)alkyl; R15 is H, (C1-4)alkyl (optionally mono-substituted OH, (C1-4)alkyloxy or di(C1-4)alkylamino), phenyl, pyridyl or COR20; R16 and R17 denote (C1-4)alkyl; or R16 and R17 together with a nitrogen atom with which they are bonded from a 4-8-member saturated heterocyclic ring; R18 and R19 denote H; R20 is (C1-4)alkyl, (C3-8)cycloalkyl or furyl; and n equals 0 or 1; or its pharmaceutically acceptable salt. The invention also relates to use of formula I compounds to prepare a medicinal agent and to a pharmaceutical composition based on formula I compound.

EFFECT: novel derivatives have catepsin S and K inhibitory activity.

9 cl, 20 ex

FIELD: chemistry.

SUBSTANCE: new compounds have formula (I) , where values of radicals R1 - R10 are as given in paragraph 1 of the formula of invention; n equals 2 or 3, --- denotes absence of substitution or a single bond; and denotes a single bond or a double bond, or to salts thereof. The invention also relates to a method of producing compounds of formula (Ic), to a NK2 receptor antagonist, to a pharmaceutical agent, to a method of antagonising the NK2 receptor, to a method of preventing or treating functional gastrointestinal diseases, as well as to use of compounds given in paragraph 1.

EFFECT: obtaining new biologically active compounds with antagonistic effect on the NK2 receptor.

31 cl, 331 ex, 7 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for producing prasugrel hydrochloride which involves the following stages: (i) chlorination of a compound described by formula (III) by addition of an chlorinating agent, optionally drop-by-drop, in a solvent; (ii) reaction of the prepared compound of formula (IV) and a compound described by general formula (V) where R means a protective group for hydroxyl, or its salt in a solvent in the presence of a base; (iii) acetylation of the prepared compound described by general formula (II) by reaction with an acetylation agent in a solvent in the presence of a base and an acetylation catalyst; and (iv) addition of hydrochloric acid, optionally drop-by-drop, to the prepared compound described by formula (I) in a solvent to produce prasugrel hydrochloride described by formula (1a), and differs by the fact that at the stage (i) temperature during addition of the chlorinating agent, optionally drop-by-drop, ranges within -20°C to 5°C, and reaction temperature after addition of the chlorinating agent, optionally drop-by-drop, ranges within -20°C to 5°C. The invention also concerns a product containing prasugrel hydrochloride and CATP in an amount no more than 0.3 %, to the pharmaceutical composition suitable for prevention or treatment of thrombosis or embolism on the basis of the specified product.

EFFECT: production of low-CATP prasugrel hydrochloride.

31 cl, 3 dwg, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to organic chemistry, more specifically to a method of olanzapine purification which involves mixing olanzapine with an organic acid in an organic solvent or a mixture of organic solvents to prepare acid-additive olanzapine salt, precipitation and isolation of acid-additive olanzapine salt and transforming acid-additive olanzapine salt in olanzapine; the organic acid is carboxylic acid which is selected from the group including oxalic, fumaric and benzoic acid.

EFFECT: invention refers to methods for producing pure olanzapine, intermediate products and acid-additive olanzapine salts which in turn can find application for producing pure olanzapine used for preparing a drug for treating mental disorders and conditions.

38 cl, 1 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where X denotes S; R1 and R2 taken together with atoms to which they are bonded form a 5-member carbocycle, substituted with up to two substitutes selected from alkyl and CF3; R3 is selected from a group consisting of a hydrogen atom and C1-8-alkyl; R3a denotes a hydrogen atom; R4 denotes a hydrogen atom; R4a denotes a hydrogen atom; R5 denotes a hydrogen atom; R5a denotes a hydrogen atom; R6 denotes a hydrogen atom; R6a denotes a hydrogen atom; R7 denotes a hydrogen atom; or pharmaceutically acceptable salts thereof. The invention also relates to compounds of the given formula, compounds selected from the group, as well as a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which modulate serotonin receptor activity.

6 cl, 19 ex, 1 tbl

FIELD: chemistry.

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

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

14 cl, 128 ex

Organic compounds // 2430921

FIELD: chemistry.

SUBSTANCE: invention relates to an azathiabenzo-azulene derivative of formula I

,

where R3 denotes C1-C6alkyl, R4 denotes OH, R5 denotes halogen and R6 denotes H or halogen, or a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds, having anti-inflammatory or analgesic action.

EFFECT: obtained compounds and pharmaceutical composition can be used to treat arthritis and arthritis-related conditions, and for relieving inflammation and pain associated with acute inflammation of body parts, primarily joints, as a result of injury or as a result of arthritic conditions or other diseased conditions.

17 cl, 8 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing prasugrel hydrochloride of the formula:

,

with low content of "ОХТР", involving preparation of free prasugrel containing "ОХТР" from 2-silyloxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine, dissolving the obtained free prasugrel in an inert solvent and optionally adding hydrochloric acid in drops to the solution for reaction.

EFFECT: novel method of producing prasugrel with low content of impurities, specifically "ОХТР" by-product.

2 cl, 6 dwg, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the formula I

, where: m equals 0, 1 or 2, where if m=0, disappears such that an open ring or single bond forms, n equals 0, 1 or 2, wherein when n=0, disappears such that an open ring or single bond forms; m' and n' are independently equal to 0, 1 or 2; X denotes a carbon atom; Y denotes a carbon or sulphur atom; provided that m and n are not equal to 0 at the same time; denotes a single or double bond, if needed; --- absence of a bond or a single bond, if needed; R1 is selected from a group comprising CN, Hal, OAIk, OH, NRCN, C(CN)=C(OH)(OAlk), SR, NRR', (Alk)p-C(O)NRR', piperidine, wherein Alk is optionally substituted with Hal or OAlk, where p=0 or 1; R3, R4, R5 and R6 are identical or different and are independently selected from a group comprising H, OAIk, Alk, Hal, OH; R2 is selected from a group comprising H and O, and p'=0 or 1; R7 is selected from a group comprising H, O, OH, N-OH, N-aryl, N-OAlk, N-O-aryl, N-O-Alk-aryl, N-NR-CONRR', N-O-CO-Alk, or 2 R7, bonded with the same Y, together form lioksalan; wherein said Alk is optionally substituted with OAlk, -CO-(NR-Alk-CO)p'-OAlk, and p'=0 or 1; R and R', which are identical or different, are independently selected from a group comprising H, and Alk; or pharmaceutically acceptable salt or optical isomer or diastereomer thereof, except those compounds for which: R3, R4, R5, R6=H, R1=CN, denotes a single bond, and denotes -C(=N-(2,4,6-trimethylphenyl))-, -C(=N-(2,6- dimethylphenyl))-, -C(=N-(2,6-diethylphenyl))-, -C(=N(2-methylphenyl))-, -C(=N(2-ethylphenyl))-, -C(=N-(2-trifluoromethylphenyl))-, -C(=N-(2-isopropylphenyl))-, -C(=N-phenyl)-, -C(=N-(naphthyl)- or -C(=O)-, -CH2-, or R3, R5, R6=H, R4=OMe, R1=CN, denotes a single bond, and denotes -C(=O)-, or R3, R4, R5, R6=H, R1=NH2, denotes a single bond, and denotes -CH2- or -CH2-CH2-; or R3, R4, R5, R6=H, R,=NH2, denotes -CH2- or -CH2-CH2-, and denotes a single bond. The invention also relates to a cysteine protease based pharmaceutical composition based on compounds of formula I, use of the compound of formula I to prepare a drug for inhibiting cysteine protease, for treating and preventing cancer, as well as inflammatory diseases and others.

EFFECT: novel compounds which can be used in medicine are obtained and described.

38 cl, 43 ex, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts exhibiting PI3 kinase inhibitor activity. In the formula (I), A represents a thiophen ring; n=1; R1 represents , where m=1; R30 represents H; R4 And R5 together with N atom whereto attached form a 5- or 6-members N-containing heterocyclic group which includes 0 or 1 additional heteroatom selected from N and O which is unsubstituted or substituted by one or more substitutes selected from C1-6alkyl, C1-6alkoxy, -N(R"')-alk-OR, -alk-OR, -O-alk-OR, -alk-C(O)NR2, -C(O)NR2, -alk-Het, -N(R)-Het, -O-Het, -N(R)-C(O)- alk-OR, -NR-S(O)2R, -N(R)-alk-S(O)2R, -N(R)-alk-OR, -alk-NR'R", -N(R"')-S(O)2R, S(O)2R"', -S(O)2-alk-ORf 5- or 6-members N-containing heterocyclic group, 5- or 6-members N-containing heteroaryl group which includes 0 or 1 additional heteroatom selected from N, O or S, oxo(=O), -SO2NR2, -SO2-alk-NR2 where alk means a C1-6alkylene chain; Het means a 5- or 6-members N-containing heteroaryl group or furan optionally substituted by C1-6alkyl; R means H or C1-6alkyl, or when 2 groups R are bound with N, they together with N atom form a saturated 5- or 6-members N-containing heterocyclic group; each R' and R" means independently H, C1-6alkyl or C1-6alkoxy; R'" represents C1-6alkyl, a 5- or 6-merous saturated N-containing heterocyclic group, or a 5- or 6-merous N-containing heteroaryl group; R2 means where R6 and R7 together with N atom whereto attached form a morpholine group; R3 represents an indazole group.

EFFECT: development of the effective method of preparing the compounds of formula (I), and their application for preparing a drug, a pharmaceutical composition, and a method of inhibition.

10 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the new fused pyrimidines of formula (I) and to their pharmaceutically acceptable salts exhibiting P13 kinase inhibitor properties; in formula (I), A represents a thiophen ring; n=1; R1 represents a group of formula , where m=1; R30 represents hydrogen; R4 and R5 together with N atom whereto attached form a 5- or 6-members saturated N-containing heterocyclic group which includes 1 additional heteroatom selected from N which is unsubstituted or substituted by C1-C3alkyl which can be substituted by OH; S(O)2C1-3alkyl; C(O)N(diC1-C3alkyl); N(CH3)2; CON(CH3)-CH2CH2OCH3; N(CH3)-CH2CH2OCH3; -C(O)morpholine or morpholine; R2 is selected from where R6 and R7 together with nitrogen atom whereto attached form a morpholine group which is unsubstituted; and R3 represents an indole group which is unsubstituted.

EFFECT: production of the compounds of formula (I), a pharmaceutical composition, their application for preparing a drug and a method of inhibition.

9 cl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to condensed heterocyclic derivative, represented by formula (I): where ring A represents 5-member monocyclic heteroaryl, containing 1 or 2 heteroatoms, selected from N or S; RA represents lower alkyl group, optionally substituted with hydroxyl group, COW1, COOW1 or CONW2W3, in which W1-W3 independently represent a hydrogen atom or lower alkyl group; m represents integer 0 or 2; ring B represents benzene ring or thiophene ring; RB represents halogen atom, cyano group, lower alkyl group or OW4, in which W4 represents a hydrogen atom or lower alkyl group; n represents integer 0-2; E1 represents an oxygen atom; E2 represents an oxygen atom; U represents a single bond or lower alkelene group; X represents group, represented by Y, -CO-Y, -SO2-Y, -S-L-Y, -O-L-Y, -CO-L-Y, -SO-L-Y, -SO2-L-Y, -S-Z or -O-Z, in which L represents a lower alkylene group optionally substituted with halogen or hydroxy group; Y represents group, represented by Z or -NW7W8, where W7 and W8 independently represent a hydrogen atom, lower alkyl group or Z on condition that W7 and W8 are not simultaneously hydrogen atoms, or W7 and W8 can bind together with adjacent nitrogen atom with formation of cyclic amino group; Z represents cycloalkyl group, optionally condensed with phenyl and optionally substituted with phenyl group, optionally substituted with halogen or alkoxy group; 6-8-member heterocycoalkyl group, which has 1 heteroatom, selected from nitrogen atom or oxygen atom, optionally condensed with phenyl and optionally substituted with phenyl; phenyl group optionally substituted with a substituent, selected from group, consisting of a halogen atom, cyano group, alkyl group, optionally substituted with halogen atom, hydroxy group or alkoxy group, alkoxy group, optionally substituted with halogen atom, hydroxy group, alkoxy group, alkoxy-carbonyl-oxy group or acyloxy group, alkylthio group, carboxy group and alkoxy-carbonyl group; pyridyl; or its pharmaceutically acceptable salt. Invention also relates to pharmaceutical composition possessing antagonistic activity with respect to gonatotropin-releasing hormone, based on the claimed compound.

EFFECT: obtained are novel compounds and based on them pharmaceutical composition, which can be applied in medicine for prevention or treatment of a disease depending on sex hormones, which is selected from group, consisting of benign prostatic hypertrophy, hysteromyoma, endometriosis, premature puberty, prostate cancer, ovarian cancer and breast cancer.

29 cl, 112 tbl, 428 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrazole derivatives of general formula I

and pharmaceutically acceptable salts thereof, where n equals 1 or 2, m equals 0, 1 or 2, A contains in the ring a group selected from -CR1=, -CR2=, -CR3=, -CR4= and -CR5=, where 0 or 1 in these groups is replaced with N, R1, R2, R3, R4 and R5 are independently selected from a group comprising hydrogen, hydroxy, halogen, cyano, cyano(C1-C6)alkyl, C4-C6 heterocycloalkyl-C0-alkyl, where the said heterocycloalkyl contains 1-2 heteroatoms selected from nitrogen and oxygen atoms, C5heteroaryl-(C0-C4)alkyl, where the said heteroaryl contains 1-4 heteroatoms selected from nitrogen atoms, -XSO2R11, -XSO2NR11R12, -XSO2NR11C(O)R12, -XC(NR11)NR11OR12, -XCR11=NOR12, -XC(O)R11, -XC(O)OR11, -XNR11R12, -XC(O)NR11R12, -XOC(O)NR11R12, -XNR11C(O)NR11R12, -XNR11XOR12; -XN(XOR12)2, -XNR11XC(O)OR12 -XNR11XNR11C(O)R12 -XNR11XNR11R12, -XNR11C(O)R12, where each X is independently selected from a group comprising a chemical bond and C1-C4alkylene, each R11 is selected from a group comprising hydrogen and C1-C6alkyl, and R12 is selected from a group comprising hydrogen, C1-C6alkyl and phenyl, or R11 and R12 together with a nitrogen atom to which R11 and R12 are bonded form C6heterocycloalkyl. Said heteroaryl or heterocycloalkyl in R1, R2, R3, R4 or R5 optionally contains one substitute selected from a group comprising hydroxyl, cyano, C1-C6alkyl, hydroxyl(C1-C6)alkyl and carboxy, R6 and R7 independently denote hydrogen, R8 is selected from a group comprising C1-C6alkyl, halogen(C1-C3)alkyl, -CH2OR8a and -COOR8a or two R8 groups bonded to different carbon atoms, together form a (C1-C2)alkyl bridge, or two R8a groups bonded to one carbon atom form a (C3-C8)cycloalkyl group, where R8a is selected from a group comprising hydrogen and C1-C6alkyl, R9 is selected from a group comprising phenyl and C6heteroaryl, where the said heteroaryl contains 1-2 heteroatoms selected from nitrogen atoms, and C9heteroaryl, where the said heteroaryl contains 1-2 heteroatoms selected from nitrogen and oxygen atoms, where the said phenyl or heteroaryl in R9 is optionally substituted with 1-2 substitutes independently selected from a group comprising halogen, cyano, hydroxy, C1-C3alkyl, halogen(C1-C3)alkyl, hydroxy(C1-C3)alkyl, -C(O)R13, -C(O)NR13R14, where each of R13 and R14 is independently selected from a group comprising hydrogen and C1-C6alkyl, R10 denotes hydrogen, Y and Z are independently selected from a group comprising CR20 and N, where R20 denotes hydrogen, provided that compounds of formula I do not include compounds of formula II, which are described in claim 1, and provided that compounds of formula I do not include compounds which are: 1-(4-fluorophenyl)-4-((3-phenyl-1H-pyrazol-4-yl)methyl)piperazine, 1- ((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(4-(trifluoromethyl)-(pyridin-2- yl)piperazine, 1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(5-(trifluoromethyl)-(pyridin-2-yl)piperazine and 1-((3-(4-fluorophenyl)-1H-pyrazol-4-yl)methyl)-4-(5-fluoropyridin-2-yl)piperazine. The invention also relates to specific compounds obtained.

EFFECT: novel pyrazole derivatives which can be used in treating diseases or disorders which are mediated by disrupted activation of the said compound are obtained.

8 cl, 1 tbl, 4 ex

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