Novel piperazine compound and use thereof as hcv polymerase inhibitor


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

 

The text descriptions are given in facsimile form.

1. The compound represented by the following formula [I-D1] or its pharmaceutically acceptable salt:

where ring a is
With3-12ring group of carbon atoms, optionally substituted by 1-5 substituents selected from the following group a, or
heterocyclic group, optionally substituted by 1-5 substituents selected from the following group a,
(where the heterocyclic group has, besides carbon atoms, 1 or 2 heteroatoms selected from nitrogen atom, oxygen atom and atom series is, where the number of atoms forming the ring is 4 to 9),
n is an integer from 1 to 3,
ring B1 is a phenyl group, optionally substituted by 1-5 substituents selected from the following group a,
ring C2 is a heterocyclic group, optionally substituted by 1-3 substituents selected from the following group a' (where the heterocyclic group has, besides carbon atoms, 1 to 6 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where the number of atoms forming the ring is 4 to 13),
group a:
the halogen atom, the nitro-group, cyano,
-ORa1,
-SRa2,
-NRa3Ra4,
-NHCORa5,
-NSO2Ra14,
-COORa6,
-CONRa7Ra8,
-SO2NRa9Ra10,
-SO2NHCORa15,
-CORa11,
-SO2Ra12,
-CONHSO2Ra13,
-COCOORa16,
-COCONRa17Ra18,
-CONRa19(ORa20),
-SF5,
(where Ra1-Ra20are the same or different, and each is
a hydrogen atom,
With1-10alkyl group, optionally substituted by 1-5 substituents selected from the following group b,
With6annular group of carbon atoms, optionally substituted by 1-5 substituents selected from the following group C, or
the heterocyclic group
(where the heterocyclic group and eat, in addition to carbon atoms, 1 or 2 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where the number of atoms forming the ring is 5 or 6)),
With1-10alkyl group, optionally substituted by 1-5 substituents selected from the following group b,
With2-10alkyl group, optionally substituted by 1-5 substituents selected from the following group b,
With3-12ring group of carbon atoms, optionally substituted by 1-5 substituents selected from the following group C, and
heterocyclic group optionally substituted by 1 or 2 substituents selected from the following group C,
(where the heterocyclic group has, besides carbon atoms, 1 to 3 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where the number of atoms forming the ring is 4 to 6),
group a':
the halogen atom, the nitro-group, cyano,
-ORa1,
-SRa2,
-NRa3Ra4,
-NHCORa5,
-NHSO2Ra14,
-COORa6,
-CONRa7Ra8,
-SO2NRa5Ra10,
-SO2NHCORa15,
-CORa11,
-SO2Ra12,
-CONHSO2Ra13,
-COCOORa16,
-COCONRa17Ra18,
-CONRa19(ORa20),
-SF5,
(where Ra1-Ra20are the same or different, and each is
a hydrogen atom,
With1-10alkyl gr is POI, optionally substituted by 1-5 substituents selected from the following group b,
With3-6annular group of carbon atoms, optionally substituted by 1-5 substituents selected from the following group C, or
With6-12aryl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the following group C),
With1-10alkyl group, optionally substituted by 1-5 substituents selected from the following group b,
With2-10Alchemilla group, optionally substituted by 1-5 substituents selected from the following group b,
With3-12ring group of carbon atoms, optionally substituted by 1-5 substituents selected from the following group C,
With6-12aryl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the following group C,
heterocyclyl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the following group C,
(where the heterocyclic fragment has, besides carbon atoms, 1 or 2 heteroatoms selected from nitrogen atom, oxygen atom and sulfur atom, where the number of atoms forming the ring is 5 or 6), and
With3-10cycloalkyl-C1-4alkyl group, optionally substituted by 1-5 substituents selected from the following group C,
group:
halogen atom, cyano, hydroxyprop is a,
With1-4alkoxygroup,
amino group,
With1-4alkylamino,
di(C1-4alkyl) amino group,
carboxyl group,
With1-4alkoxycarbonyl group,
carnemolla group,
With1-4alkylaminocarbonyl group,
di(C1-4alkyl) aminocarbonyl group and
three(C1-4alkyl) ammonitella group,
group:
halogen atom, cyano, hydroxy-group,
carboxyl group,
With1-4alkyl group,
halogen-C1-4alkyl group,
hydroxy-C1-4alkyl group,
carboxy-C1-4alkyl group,
With1-4alkoxy-C1-4alkyl group,
With1-4alkoxygroup and
carboxy-C1-4alkoxygroup.

2. The compound according to claim 1, where ring a is a phenyl group, optionally substituted by 1-5 substituents selected from group a, or its pharmaceutically acceptable salt.

3. The compound according to claim 1, where n is equal to 1, or its pharmaceutically acceptable salt.

4. The compound according to claim 1, where the ring C2 is a heterocyclic group, optionally substituted by 1-3 substituents selected from group a', and a heterocyclic group selected from the group consisting of imidazolinone group, thiazolidine group, oxazolidine group, thienyl group, dioxopyrimidine group, dioxopyrimidine group, oxopyrrolidin the school group, oxothiazolidine group, tetrahydroisoquinolines group, thiazolidine group, thiadiazolyl group, pyrazolidine group, imidazolidine group, triazolines group, oxazoline group, peredelnoj group, pyrimidines group, personalni group, pyridazinyl group,
pinolillo group,
[1,5]naphthyridine group,
[1,6]naphthyridine group,
oxopiperidine group,
oxopiperidine group,
[1,2,4]triazolo[1,5-a]pyrimidines group,
benzimidazolyl group,
imidazo[4,5-C]pyridinoline group,
khinoksalinona group,
pyrido[2,3-b]personalni group,
pyrido[3,4-b]personalni group,
pteridinyl group,
pyrazino[2,3-b]personalni group,
imidazo[4,5-b]personalni group,
2,2-dioxo-1,2,3,4-tetrahydropyrazino[2,3-C][1,2,6]thiadiazolidine group,
2-oxo-1,4-dihydropyrido[2,3-d][1,3]oxazinyl group,
2-oxo-2,3-dihydroimidazo[4,5-b]personalni group,
[1,2,5]thiadiazolo[3,4-b]personalni group,
benzothiazolyl group,
4,5,6,7-tetrahydroindazole group,
thiazolo[5,4-b]pyridinoline group,
thiazolo[5,4-C]pyridinoline group,
thiazolo[4,5-d]pyrimidines group,
thiazolo[5,4-d] pyrimidines group,
thiazolo[4,5-d]pyridazinyl group,
thiazolo[4,5-b]personalni group,
thiazolo[4,5-d][1,2,3]triazinyl the group,
5-oxo-4,5-dihydrothiazolo[5,4-b]pyridinoline group,
pyrazolo[3,4-d]thiazoline group,
4,6-dioxo-5,6-dihydropyrrolo[3,4-d]thiazoline group,
4,5,6,7-tetrahydrothieno[5,4-C]pyridinoline group,
4-oxo-4,5,6,7-tetrahydropyrazolo[5,4-C]pyridinoline group,
4-oxo-4,5-dihydrothiazolo[5,4-C]pyridinoline group,
7-oxo-6,7-dihydrothiazolo[4,5-d]pyrimidines group,
4-oxo-4,5-dihydrothiazolo[4,5-d]pyridazinyl group,
7-oxo-6,7-dihydrothiazolo[4,5-d]pyridazinyl group,
4,7-dioxo-4,5,6,7-tetrahydropyrazolo[4,5-d]pyridazinyl group,
4-oxo-3,4-dihydrothiazolo[4,5-d][1,2,3]triazinyl group,
5-oxo[1,3,4]thiadiazolo[3,2-a]pyrimidines group,
7-oxo[1,3,4]thiadiazolo[3,2-a]pyrimidines group,
4-oxo[1,3,4]thiadiazolo[2,3-C][1,2,4]trainline group,
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazolyl group and
intentionally group,
or its pharmaceutically acceptable salt.

5. The compound according to claim 4, where the ring C2 is thiazol-2-ilen group optionally substituted by 1 or 2 substituents selected from group a', or its pharmaceutically acceptable salt.

6. The compound according to claim 4, where the ring C2 is a heterocyclic group, optionally substituted by 1-3 substituents selected from group a', and a heterocyclic group selected from the group consisting of
benzothiazole-2-ilen group,
4,5,6,7-tetrahydroindazole-2-the school group,
thiazolo [5,4-b] pyridine-2-ilen group,
thiazolo[5,4-C]pyridine-2-ilen group,
thiazolo[4,5-d]pyrimidine-2-ilen group,
thiazolo[5,4-d]pyrimidine-2-ilen group,
thiazolo[4,5-d]pyridazin-2-ilen group,
thiazolo[4,5-b]pyrazin-2-ilen group,
thiazolo[4,5-d][1,2,3]triazine-6-ilen group,
5-oxo-4,5-dihydrothiazolo[5,4-b]pyridine-2-ilen group,
1H-pyrazolo[3,4-d]thiazole-5-ilen group,
4,6-dioxo-5,6-dihydro-4H-pyrrolo[3,4-d]thiazole-2-ilen group,
4,5,6,7-tetrahydrothieno[5,4-C]pyridine-2-ilen group,
4-oxo-4,5,6,7-tetrahydropyrazolo[5,4-C]pyridine-2-ilen group,
4-oxo-4,5-dihydrothiazolo[5,4-C]pyridine-2-ilen group,
7-oxo-6,7-dihydrothiazolo[4,5-d]pyrimidine-2-ilen group,
4-oxo-4,5-dihydrothiazolo[4,5-d]pyridazin-2-ilen group,
7-oxo-6,7-dihydrothiazolo[4,5-d]pyridazin-2-ilen group,
4,7-dioxo-4,5,6,7-tetrahydropyrazolo[4,5-d]pyridazin-2-ilen group,
4-oxo-3,4-dihydrothiazolo[4,5-d][1,2,3]triazine-6-ilen group,
5-oxo-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-2-ilen group,
7-oxo-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-2-ilen group,
4-oxo-4H-[1,3,4]thiadiazolo[2,3-C][1,2,4]triazine-7-strong group,
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole-6-ilen group and intentionally group,
or its pharmaceutically acceptable salt.

7. The compound according to claim 4, where the ring C2 is pyrazin-2-ilen group, optionally substituted by 1-3 substituents, selected the C group a', or its pharmaceutically acceptable salt.

8. The compound according to claim 4, where the ring C2 is a heterocyclic group, optionally substituted by 1-3 substituents selected from group a', and a heterocyclic group selected from the group consisting of
cinoxacin-2-ilen group,
pyrido[2,3-b]pyrazin-2-ilen group,
pyrido[2,3-b]pyrazin-3-ilen group,
pyrido[3,4-b]pyrazin-2-ilen group,
pteridine-6-ilen group,
pteridine-7-strong group,
pyrazino[2,3-b]pyrazin-2-ilen group,
1H-imidazo[4,5-b]pyrazin-5-ilen group,
2,2-dioxo-1,2,3,4-tetrahydropyrazino[2,3-C][1,2,6]thiadiazin-7-strong group,
2-oxo-1,4-dihydro-2H-pyrazino[2,3-d][1,3]oxazin-7-strong group,
2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyrazin-5-ilen group and
[1,2,5]thiadiazolo[3,4-b]personalni group,
or its pharmaceutically acceptable salt.

9. The compound represented by the formula:

or its pharmaceutically acceptable salt.

10. The compound represented by the formula:

or its pharmaceutically acceptable salt.

11. The compound represented by the formula:

or its pharmaceutically acceptable salt.

12. The compound represented by the formula:

or its pharmaceutically acceptable salt.

13. The connection represented by FD is moloi:

or its pharmaceutically acceptable salt.

14. The compound represented by the formula:

or its pharmaceutically acceptable salt.

15. The compound represented by the formula:

or its pharmaceutically acceptable salt.

16. The compound represented by the formula:

or its pharmaceutically acceptable salt.

17. The compound represented by the formula:

or its pharmaceutically acceptable salt.

18. The compound represented by the formula:

or its pharmaceutically acceptable salt.

19. The compound represented by the formula:

or its pharmaceutically acceptable salt.

20. The compound represented by the formula:

or its pharmaceutically acceptable salt.

21. The compound represented by the formula:

or its pharmaceutically acceptable salt.

22. The compound represented by the formula:

or its pharmaceutically acceptable salt.

23. The compound represented by the formula:

or its pharmaceutically acceptable salt.

24. The pharmaceutical composition, the possession is based on inhibitory activity against HCV polymerase, containing the compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

25. Antiviral agent containing the compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

26. Therapeutic tool for the treatment of hepatitis C, containing as active ingredient a compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt.

27. The use of compounds according to any one of claims 1 to 23 or its pharmaceutically acceptable salt to obtain anti-HCV funds.

28. The use of compounds according to any one of claims 1 to 23 or its pharmaceutically acceptable salt to obtain an inhibitor of HCV polymerase.

29. A method of treating hepatitis C in a mammal, comprising introducing an effective amount of a compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt to a mammal.

30. Method of inhibiting HCV polymerase in a mammal, comprising administration to the mammal of an effective amount of a compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt.

31. Pharmaceutical composition for treating hepatitis C, which contains the compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

32. Pharmaceutical composition for inhibiting HC polymerase, containing the compound according to any one of claims 1 to 23 or its pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.



 

Same patents:

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: chemistry.

SUBSTANCE: invention relates to a method of photoactivation of a photocatalyst by irradiating a composition containing the said catalyst. The method of using a photolatent catalyst (a) in which a composition containing said catalyst is irradiated before subsequent treatment is characterised by that, the photolatent catalyst is: (a1) a compound selected from a group consisting of a photolatent acid, an aromatic iodonium salt or oxime-based photolatent acid; (a2) a photolatent base compound. Also described is a substrate on which a coating made from the composition is deposited in accordance with the above described method. Also described is a method of using photolatent catalyst (a), in which a composition containing said catalyst is irradiated before subsequent treatment, characterised by that subsequent treatment is preparation of foam material and the composition contains polyol and isocyanate components and photolatent base (a2) as photolatent catalyst.

EFFECT: provision for solidification of the system.

13 cl, 10 tbl, 16 ex

FIELD: pharmacology.

SUBSTANCE: present invention refers to compounds of formula (I) , to its N-oxides, salts, stereoisomer forms where n is equal 1, 2 or 3; R1 means cyano group; X means bivalent radical NR2 or O; R2 means hydrogen or C1-10alkyl, each Q1 independently stands for direct coupling, -CH2- or -CH2-CH2-; each R4 independently means hydrogen or C1-4alkyl; each R5a, R5b, R5c independently means hydrogen, C1-4alkyl or arylC1-4alkyl; each R5e, R5f independently means hydrogen, C1-4alkyl or arylC1-4alkyl, or R5e and R5f together can form bivalent alkandiyl radical of formula -CH2-CH2- or -CH2-CH2-CH2-; R11 means aryl, arylC1-4alkyl, C1-4alkylcarbonyl, arylcarbonyl, arylC1-4alkylcarbonyl, C1-4alkyloxycarbonyl, arylC1-4alkyloxycarbonyl, R5aR5bN-carbonyl, hydroxyC1-4alkyl, C1-4alkyloxyC1-4alkyl, arylC1-4alkyloxyC1-4alkyl, aryloxyC1-4alkyl, pyridyl; -a1=a2-a3=a4- means a bivalent radical of formula -CH=CH-CH=CH- (c-1); where one or two hydrogen atoms in (c-1) are substituted by radical C1-6alkyl, C1-4alkoxy, halogen, hydroxy group, (R5g)(R5h)N-(C1-4alkandiyl)-O-trifluoromethyl, cyano group, radical -COOR4, (R5a)(R5b)N-sulphonyl, pyrrolidinyl-sulphonyl, piperidinyl sulphonyl, radical N(R5a)(R5b), radical (a-1), (a-7), morpholinyl, (R5g)(R5h)N-(C1-4alkandiyl)-N(R5c)-, C1-6alkylcarbonylamino, C1-6alkyloxycarbonylamino, C1-6alkylsulphonylamino, (R5a)(R5b)N-C1-4alkyl; R20 means hydrogen, spiro (C2-4alkylenedioxy), spiro (diC1-4alkyoxy) or -NR5gR5h; each R5g or R5h independently means either hydrogen, or C1-4alkyl, or R5g and R5h together with nitrogen atom whereto attached form pyrrolidinyl, piperidinyl or morpholinyl; R3 means nitro group, cyano group, amino group, halogen, hydroxy group or C1-4alkoxy; aryl means phenyl optionally substituted with one or more substitutes chosen from the group consisting of C1-6alkyl, C1-4alkoxy, halogen, hydroxy, amino and trifluoromethyl. Besides it relates to the pharmaceutical composition with antiviral activity, and method for making said compounds.

EFFECT: there are prepared and described new compounds with antiviral activity.

9 cl, 15 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a dynamic nuclear polarisation method of a compound which contains one or more carboxyl groups, distinguished by that, the radical of formula (I) , where M is one equivalent cation of an alkali metal; and R1, which are identical or different, each represents a C1-C6-alkyl group with a straight or branched chain or a -(CH2)n-X-R2 group, where n equals 1, 2 or 3; X is O; and R2 is a C1-C4alkyl group with a straight or branched chain, which are used a paramagnetic agent in the said dynamic nuclear polarisation process. The invention also relates to new radicals, to their use as paramagnetic agents.

EFFECT: obtaining new radicals of formula (I), which are used as paramagnetic agents in dynamic nuclear polarisation processes.

17 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a liquid composition which contains hyperpolarised 13C-pyruvate, involving: a) formation of a liquid mixture containing a radical of formula (I) , where M is hydrogen or one equivalent cation; and R1, which are identical or different, each represents hydroxylated and/or alkoxolated C1-C4-hydrocarbon group with a straight or branched chain, 13C-pyroracemic acid and/or 13C-pyruvate, and freezing this mixture; b) increasing polarisation of 13C nuclei of pyroracemic acid and/or pyruvate in this mixture through dynamic nuclear polarisation c) addition of a physiologically transferable buffer, which provides for pH in the range from 7 to 8, and a base to the frozen mixture for its dissolution and for converting 13C-pyroracemic acid to 13C-pyruvate, obtaining a liquid composition or, when at stage (a) only 13C-pyruvate is used, addition of a buffer to the frozen mixture for its dissolution, obtaining a liquid composition; and d) possible removal of the radical and/or its reaction products from the liquid composition. The invention also relates to use of such a composition and to a radical of formula (I).

EFFECT: obtaining a composition for use as MP of a visualising agent.

22 cl, 2 dwg, 5 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds with formula I: , where D is O; E is CH2 or O; n equals 1 or 2, and R1 is chosen from hydrogen, halogen or substituted or unsubstituted 5- or 6-member aromatic or heteroaromatic ring with 0, 1 or 2 nitrogen atoms, 0 or 1 oxygen atom, or is chosen from substituted or unsubstituted 8-, 9- or 10-member condensed heteroaromatic ring system with 0 or 1 nitrogen atom, 0 or 1 oxygen atom, where the said aromatic or heteroaromatic rings or ring systems, when they are substituted, have substitutes which are chosen from -C1-C6alkyl, -C3-C6cycloalkyl, -C1-C6alkoxy, halogen, -CF3, -S(O)mR2, where m equals 0, 1 or 2, -NR2R3, -NR2C(O)R3 or -C(O)NR2R3; R2 and R3 are in each case independently chosen from hydrogen, -C1-C4alkyl, -C3-C6cycloalkyl, aryl; or its stereoisomers, enantiomers or pharmaceutically acceptable salts; under the condition that the given compound is not 2-(1-aza-bicyclo[2.2.2]oct-3-yl)-2,3-dihydroisoindol-1-one. The invention also relates to compounds with formulae II or III, to a pharmaceutical composition, as well as to use of compounds in paragraph 1.

EFFECT: obtaining new biologically active compounds with activity towards alpha 7 nicotinic acetylcholine receptors (α7 nAChRs).

8 cl, 72 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to the new compounds of formula I in the form of the salt or zwitter-ion, wherein R1 and R3 are independently phenyl, C3-C8 cycloalkyl or thienyl group, R2 is haloid or hydroxyl group; R4 is C1-C8 alkyl substituted with -NR5-CO-R6 or -CO-NR9R10; R5 is hydrogen ; R6 is C1-C8alkyl or C1-C8 alkoxy, each of them is optionally substituted with 5- or 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R6 is 5-10-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur; R9 is hydrogen or C1-C8alkyl; R10 is C1-C8alkyl, optionally substituted with cyano group, C1-C8 alkoxy group or with 5- or 6-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur, or R10 is 5-9-membered heterocyclic group containing at least one ring heteroatom selected from nitrogen, oxygen and sulphur. The invention refers also to the pharmaceutic composition, to the application of compound of any of claims 1-5 as well as to the preparation method of compound of formula I of claim 1.

EFFECT: preparation of the new biologically active compounds taking the effect of muscarin receptor M3.

9 cl, 247 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to derivatives of 1,4-diazabicyclo[3,2,1]octanecarboxamide with general formula (1) , in which X is a nitrogen atom, P and W each independently represent a nitrogen atom or a group with general formula C-R3, Q and R each independently represent a group with general formula C-R3, R1 is a hydrogen atom, R3 is a hydrogen atom or halogen or C1-C6-alkyl, C1-C6-alkoxy, O-Ms. The invention also relates to a medicinal preparation and pharmaceutical composition based on these compounds for treating or preventing disorders, related to malfunction of nicotinic receptors.

EFFECT: obtaining new compounds and a pharmaceutical composition based on the said compounds, which can be used for treating cognition failure and attention failure, or for treating motor, neurological or alerting symptoms related to dependency on different addictive substances.

5 cl, 2 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to derivatives of 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidine-2(3H)-one of formula (I) where R1 represents CH3 or CH3CH2; R2 represents H, 3-CN, 2-CF3, 2-F, 3-F, 3-CF3, 3-CONH2 or SO2CH3; R3 represents H; R4 represents H or CH3; and R5 represents H; or, when R4 represents CH3, R5 represents H or F; and to its pharmaceutically acceptable salts. Also, the invention refers to a pharmaceutical composition exhibiting properties of CX3CR1 receptor antagonist containing compound (I) of formula or its pharmaceutically acceptable salt mixed with a pharmaceutically acceptable diluent or carrier.

EFFECT: enabled administration of the derivatives of 5,7-disubstituted [1,3]thiazolo[4,5-d]pyrimidine-2(3H)-one as selective CX3CR1 receptor antagonists.

13 cl, 1 tbl, 20 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-cyclohexylaminomethylthiazole[3,2-a]benzimidazole dihydrochloride of formula I: , having immunotropic and anti-aggregation activity.

EFFECT: novel compounds have useful biological properties.

2 cl, 8 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds which possess inhibiting properties with respect to PI3-kinase of general formula (1), where R1 is selected from group, including -NHRC, -NHC(O)Rc, -NHC(O)ORc, -NHC(O)NRcRc and -NHC(O)SRc, R2 stands for residue, optionally substituted with one or two substituents R4, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, 5-6-member heterocycloalkyl with one heteroatom, selected from nitrogen and sulphur, phenyl, benzyl and 5-6-member heteroaryl, including 1-2 nitrogen atoms, R3 stands for optionally substituted with one or several substituents Re and/or Rf residue, selected from group, including phenyl and 5-6-member heteroaryl with 1-3 heteroatoms, selected from nitrogen and oxygen, R4 represents residue, selected from group, including Ra, Rb, and substituted with one or several identical or different substituents Rc and/or Rb , Ra in each case is independently selected from group, including C1-C6alkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 9-member heteroaryl with one atom of nitrogen as heteroatom, Rb in each case is independently selected from group, including =O, -ORc, -NRCRC, halogen, -CF3, -CN, -S(O)Rc, -C(O)Rc, -C(O)ORc, -C(O)NRcRc, -C(O)N(Rg)NRcRc, -N(Rg)C(O)Rc, -N(Rg)S(O)2Rc, -N(Rg)S(O)2NRcRc, -N(Rg)C(O)ORc and -N(Rg)C(O)NRcRc, RC in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents R and/or Re residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, C6-C9aryl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 5-6-member heteroaryl with 1-2 heteroatoms, selected from nitrogen, oxygen and sulphur, Rd in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents Re and/or Rf residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 5-10-member heteroaryl with one atom of nitrogen, Re in each case is independently selected from group, including =O, -ORf, -SRf, -NRfRf, -CN, -S(O)2Rf, -C(O)Rf, -C(O)ORf, -C(O)NRfRf and -OC(O)Rf, Rf in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents Rg residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen and 5-6-member heteroaryl with one heteroatom, selected from nitrogen and sulphur, Rg in each case independently represents hydrogen, C1-C6alkyl, C3-C8cycloalkyl and 4-7-member heterocycloalkyl with one nitrogen as heteroatom, as well as to their pharmaceutically harmless acid-additive salts. Invention also relates to compounds, used as intermediate products of synthesis of formula (I) compounds, pharmaceutical composition and application of compounds for preparation of medication, possessing properties of PI3-kinase inhibitor.

EFFECT: elaborated are novel compounds, which possess properties of PI3-kinase inhibitor.

11 cl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula (I) and formula (II), their tautomers and pharmaceutically acceptable salts. In formula (I) and in formula (II), X - S; R1 - H; R2 - NR5R6; R3 - 5-6-member heteroaryl with 1 heteroatom, selected from N and S, or phenyl, optionally substituted with one or two substituents, selected from halogen, amino, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-halogenalkyl and C1-C6-halogenalkoxy; R4 - H, C1-C6 alkyl, C1-C6 alkoxy or XR3, where X and R3 are determined above; R5 - H; R6 - H; L - N or CR7, where R7 - H; M - S. Invention also relates to pharmaceutical composition, containing as active component invention compound, to method of inhibiting activity of caseinkinase lε and to method of obtaining compounds of formula (I) or formula (II).

EFFECT: compounds of claimed invention possess properties of casein kinase lε inhibitors.

13 cl, 5 tbl, 44 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described novel acylsulfonamide peri-substituted condensed bicyclic compounds of general formula (I), values of radicals are given in invention formula. Also described is pharmaceutical composition based on formula (I) compound.

EFFECT: compounds can be used for inhibition of prostaglandin E2 binding with receptor EP3.

30 cl, 371 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: compounds can be used to treat diseases mediated by the nicotinic acetylcholine receptor, such as derangement of memory. In general formulae , and A is an indazolyl, benzothiazolyl or isobenzothiazolyl group which corresponds to structural formulae a) to c) respectively or X is O; R1 is H, F, Cl, Br, I, cycloalkyl containing 3-7 carbon atoms, alkoxy which contains 1-4 carbon atoms, fluorinated alkoxy which contains 1-4 carbon atoms, Ar or Het; ; R2 is H; R3 is H; R4 is H, F, Cl, Br, I, cycloalkyl which contains 3-7 carbon atoms, alkoxy which contains 1-4 carbon atoms, fluorinated alkoxy which contains 1-4 carbon atoms, Ar or Het; R5 is H; Ar is an aryl group containing 6 carbon atoms which is unsubstituted or substituted once or several times with halogen; and Het is a 5- or 6-member heteroaromatic group containing a heteroatom in the ring which is selected from N, O and S, or a 6-member saturated heterocyclic group which contains a heteroatom in the ring which is selected from N and O; and their pharmaceutically acceptable salts, where, if the said compound has formula I, the indazolyl group of group A is bonded through its 3rd, 4th or 7th position, the benzothiazole group of group A is bonded through the 4th or 7th position, the isobenzothiazole group of group A is bonded through the 3rd, 4th or 7th position.

EFFECT: obtaining compounds with properties of nicotinic acetylcholine receptor (nAChR) ligands, and pharmaceutical compositions based on the said compounds.

53 cl, 95 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new compounds of formula I. In general formula I A is C or N; B, D and E independently represent CR4, NR5, N, O or S; and a ring containing groups A, B, D, E, selected from thienyl, furan, imidazole, oxazole, isothiazole, thiazole, pyrrol, pyrazole; provided that: b) when A is N, not any of B, D, E can be O or S; and c) when A is C, B is CR4 and one of D or E is N or NR5, when any of D or E cannot be NR5 or N; G is N or C; R1 represents one or more substitutes selected from H, Ra halogen, -OH and -ORa; R2 represents one or more substitutes selected from H, halogen and C1-6-alkyl, and also one of substitutes R2 can be -ORb' , -NRb' Rb', -SRb', -SORb', -SO2Rb', -SO2NRb' Rb'; R3 is H, or Cy, selected from phenyl optionally substituted with one or more substitutes selected from Rc , where Rc independently represents halogen, -ORg', where Rg' independently represents a Rg group, where Rg is C1-6-alkyl; each R4 independently represents H, Re, halogen, -CORe', -CO2Re', -CONRe'Re', -NRe'Re'; R5 independently represents H, Re, -CORe, -CONReRe, -SORe or -SO2Re; each Ra independently represents C1-6-alkyl or halogen- C1-6-alkyl; each R independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rb' independently represents H or Rb; each Rc independently represents halogen, -ORg', -CONRg'Rg', -NRg'Rg'; Rd is Cy optionally substituted with one or more Rf substitutes; each Rc independently represents C1-6-alkyl optionally substituted with one or more substitutes selected from Rc and Cy*, or Re is Cy, where any of the groups Cy or Cy* can optionally be substituted with one or more substitutes selected from Rc and Rg ; each Re' independently represents H or Re; each Rf independently represents a halogen, -ORh', -CO2Rh; each Rg independently represents Rd or C1-6-alkyl optionally substituted with one or more substitutes selected from Rd and Rf; each Rg' independently represents H or Rg; each Rh independently represents C1-6-alkyl, halogen-C1-6-alkyl or hydroxy- C1-6-alkyl; each Rh' independently represents H or Rh; and Cy or Cy* given in definitions above is a partially saturated, saturated or aromatic 3-7-member monocyclic carbocyclic ring which optionally contains 1-2 heteroatoms selected from N and O, and where the ring or rings can be bonded to the remaining part of the molecule through a carbon or nitrogen atom.

EFFECT: obtaining formula I compounds with p38-kinase inhibitory properties which can be used in making drugs for treating such diseases as tumour immune and autoimmune diseases etc.

21 cl, 10 dwg, 8 tbl, 57 ex

FIELD: chemistry.

SUBSTANCE: described is a bromohydrate of 4-methoxy-7,7-dimethyl-9-(5'-carboxyamyl)amino-6H-7,8-dihydropyrimido-(4,5-b)-1,4-benzthiazine (hereinafter methiazine) and a method for synthesis of the said compound. Methiazine has anti-tumour and anti-reductase activity, which has cytostatic and cytotoxic effect which inhibits synthesis of nucleic acids and can be used in medicine. Bromohydrate of 4-methoxy-7,7-dimethyl-9-(5'-carboxyamyl)amino-6H-7,8-dihydropyrimido-(4,5-b)-1,4-benzthiazine of formula I , is obtained by reacting dimedone with ω-amino caproic acid in a medium of boiling isopropanol to obtain enamine-ketone which is subjected to bromation with bromosuccinimide with further treatment with 4-methoxy-5-amino-6-mercaptopyrimidine in a medium of boiling isopropanol.

EFFECT: improved method.

2 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (1) and their pharmaceutically acceptable salts as chemokine receptor CCR3 activity modulators, a pharmaceutical composition based on the said compounds, to synthesis method and use thereof. Said compounds can be used for treating and preventing diseases mediated by chemokine receptor CCR3 activity, such as inflammatory and allergic diseases etc. In general formula , R1 represents phenyl, [1,2,4]triazolo[4,3-a]pyridinyl, thiazolo [5,4-b]pyridinyl, benzothiazolyl, benzoxazolyl, pyridinyl, where each of the said phenyl or heterocycles can be substituted with one, two or three radicals R2; R2 each independently represents (C1-C6)halogenalkyl, halogen, COOR3; CONR3R4; R3 represents H or (C1-C6)alkyl; R4 represents H or (C1-C6)alkyl, R5 represents (C1-C6)alkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyl; R6 each independently represents (C1-C6)alkoxy, (C1-C6)halogenalkyl, halogen, OR3, CN, CONR3R4; A represents C(CH3)2-CH2-CH2-, CH2-CH2-CH2- or B represents phenyl; D-E represents CH-CH2- or C=CH-, X-W-V represents N-C=CR7 or C=C-NR7; R7 represents H or (C1-C6)alkyl; Y represents NR4, O, S(O)n; i, j, m each equals 1, n equals 0 or 2.

EFFECT: increased effectiveness of using said compounds.

13 cl, 37 ex

FIELD: medicine.

SUBSTANCE: invention is related to derivatives of isothiourea of formula I, including their pharmaceutically acceptable salts, which possess properties of antagonist CXCR4. In compounds of formula I , where R1 means remainder of formula (a) , (b) or (c) , R2 means -(CR22R23)1-3-, R3 and R8 each means S, R4 and R5 each independently means C3-C12cycloalkyl, C1-C12alkyl or saturated C8-C12 polycyclic hydrocarbon remainder, such as adamantine, non-substituted phenyl or non-substituted benzyl unnecessarily substituted with group R25, R6 means H or C1-C6alkyl, R7 means CH, R9 means direct connection or -(CR22R23)1-2-, R10-R15 each means H, R16-R23 each independently means H, C1-C6alkyl, or R20 and R21 together with carbon atoms, to which they are connected, create a benzene ring, and R25 has one of values given above for R16-R23.

EFFECT: improved method for production of derivatives of isothiourea.

5 cl, 1 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to methods for synthesis of compounds of formula (A), where R1 denotes halogen, C1-C6halogenalkyl, C1-C6alkoxy(C1-C6)alkyloxy or C1-C6alkoxy(C1-C6)alkyl; R2 denotes halogen, C1-C4alkyl or C1-C4alkoxy; R3 and R4 independently denote a branched C3-C6alkyl; and R5 denotes C3-C12cycloalkyl, C1-C6alkyl, C1-C6hydroxyalkyl, C1-C6alkoxy(C1-C6)alkyl, C1-C6alkanoyloxy(C1-C6)alkyl, C1-C6aminoalkyl, C1-C6alkylamino(C1-C6)alkyl, C1-C6dialkylamino(C1-C6)alkyl, C1-C6alkanoylamino(C1-C6)alkyl, HO(O)C-(C1-C6)alkyl, C1-C6alkyl-O-(O)C-(C1-C6)alkyl, H2N-C(O)-(C1-C6)alkyl, C1-C6alkyl-HNC(O)-(C1-C6)alkyl or (C1-C6alkyl)2N-C(O)-(C1-C6)alkyl, or their pharmaceutically acceptable salts which have renin inhibiting activity, as well as to basic intermediate compounds obtained during steps for synthesis of the desired compounds and to methods for synthesis of said intermediate compounds.

EFFECT: alternative synthesis method.

43 cl, 8 dwg, 11 ex

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