Histone deacetylase inhibitors


FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I) , where is a substituted 5-member heteroaryl ring selected from thienyl, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl, W is selected from a group comprising N and -C=; M is selected from a group comprising -C(O)N(R1)OR2, -CXCONR1R2 and -C(O)OR1, or M is -C1-C2alkyl-C(O)N(R1)OR2, wherein is , R1 and R2 are independently selected from a group comprising -H, C1-C3-alkyl, C6-aryl, and C1-C3-alkyl-C6-aryl; R is selected from a group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1 and C6aryl; n is an integer from 0 to 1; L and Y are as indicated in the claim; and to compounds of formula (II) , where L2 is selected from a group comprising H, - C0-C3alkyl- C6aryl, -C0-C3alkyl-heteroaryl, where the heteroaryl is pyridyl; -C1-C6alkyl, Y and M are the same as for compounds of formula (I). The invention also relates to a pharmaceutical composition based on compounds (I) and (II), having inhibiting action on histone deacetylase (HDAC), a method of inhibiting and a method of treating a disease which is sensitive to the HDAC inhibitor.

EFFECT: compounds of formula I and II as histone deacetylase inhibitors.

18 cl, 18 dwg, 10 tbl, 19 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

and its N-oxides and pharmaceutically acceptable salts, where
represents a substituted 5-membered heteroaryl ring selected from tanila, thiazolyl, oxazolyl, pyrrolyl, imidazolyl or pyrazolyl;
whereis thienyl,has the structure
,or;
W is chosen from the group comprising N and-C=;
M is chosen from the group comprising-C(O)N(R1OR2, -C(O)NR1R2and-C(O)OR1or
M is-C1-C2alkyl-C(O)N(R1OR2while represents,;
R1and R2independently selected from the group comprising-H, C1-C3-alkyl, C6-aryl and C1-C3-alkyl-C6-aryl;
R is chosen from the group comprising H, C1-C3alkyl, halogen, NR1R2, -OR1and C6-aryl;
n is an integer from 0 to 1;
L is chosen from the group comprising C6-aryl, heteroaryl selected from benzimidazolyl, furil, benzothiazyl, pyridinyl, benzothiazolyl, tanila and pyrrolyl; heterocyclyl representing piperidinyl; condensed heterocyclyl selected from dihydrobenzofuranyl, dihydrobenzofuranyl, benzodioxole, dibenzazepine or dihydroquinoline; -C6-aryl-heteroaryl where heteroaryl choose from tienie and pyrrolyl; -heteroaryl-C6-aryl, where heteroaryl is thienyl, -C1-C3quinil-aryl, -O-C0-C4alkyl-C6-aryl, -C1-C4alkyl-C6-aryl, -SO2NR1-C0-C4alkyl-C6-aryl, -NR1-C6-aryl, -t-Bu and-NR1SO2-C6-aryl, wherein each aryl, heteroaryl and heterocyclyl optionally substituted from 1 to 3 independently selected substituents: C6-aryl, C1-C3alkyl, halogen, -NR1R2, -OR1, -CF3, -NR1SOsub> 2-C6-aryl, nitro, oxo, and-C(O)NH-C0-C3alkyl-C6-aryl, where aryl optionally substituted from 1 to 3 substituents which are selected from
-NR1R2and tanila; wherenot necessarily connected to the heterocycle-aryl or heteroaryl in L through communication or bridging substituent;
Y is chosen from the group comprising H, C6-aryl, -C1-C4alkyl, heterocyclyl representing piperidinyl; heteroaryl representing thienyl, pyridinyl or benzothiophene; -C0-C3alkyl-C6-aryl, -C0-C3alkyl-heteroaryl where heteroaryl is thienyl; -C6-aryl-heterocyclyl where heterocyclyl choose from indolinyl and morpholinyl; -C6-aryl-O-C0-C4alkyl-C6-aryl, CF3, -N(Rc)(Rd), -C0-C3alkyl-heterocyclyl where heterocyclyl choose from dibenzazepine and dihydrobenzofuranyl; -C(O)NH-C0-C3alkyl-C6-aryl, -NHS(O)2-C0-C3alkyl-C6-aryl, -NHS(O)2-C0-C3alkyl-heteroaryl where heteroaryl is thienyl; -NHC(O)-C0-C3alkyl-C6-aryl, heterocyclyl-C(O)-O-C1-C3alkyl, where heterocyclyl is piperidinyl; -heterocyclyl-S(O)2-C0-C3alkyl-C6-aryl, where heterocyclyl depict is to place piperidinyl; -heterocyclyl-S(O)2-C0-C3alkyl-heteroaryl where heterocyclyl is piperidinyl and heteroaryl represents indolyl; -heterocyclyl-C(O)-C0-C3alkyl-C6-aryl, where heterocyclyl is piperidinyl; heterocyclyl-C(O)-C0-C3alkyl-C1-C3alkyl, where heterocyclyl is piperidinyl; -heterocyclyl-C0-C3alkyl-C6-aryl, where heterocyclyl is piperidinyl; -heterocyclyl-C(O)-C6-aryl, where heterocyclyl is piperidinyl; -CH(C6-aryl)2geterotsiklicheskikh-heterocyclyl-C(O)-heterocyclyl where heterocyclyl choose from pyrrolidinyl and piperidinyl; -heterocyclyl-C(O)-O-C1-C3alkyl, where heterocyclyl is piperidinyl; -heterocyclyl-SO2-C1-C3alkyl, where heterocyclyl is piperidinyl; -heterocyclyl-SO2-C6-aryl, where heterocyclyl is piperidinyl; -heterocyclyl-C1-C4alkyl-heteroaryl where heterocyclyl is piperidinyl and heteroaryl represents pyridinyl or indolyl; -heterocyclyl-C1-C3alkyl-C6-aryl, where heterocyclyl is piperidinyl; -heterocyclyl-SO2-C6-aryl-N(R1)-C(O)-C1-C3alkyl, -C1-C3 alkyl-O-C6-aryl, -C1-C3alkyl-O-C(O)-N(R1)-C1-C3alkyl-C6-aryl, alkylaryl-C(O)-N(R1)-C6-aryl, alkylaryl-N(R1)-SO2-C1-C3alkyl-C6-aryl, -N(R1)-SO2-C6-aryl, -N(R1)-SO2-heteroaryl, C6-aryl-O-C0-C4alkyl-heterocyclyl where heterocyclyl represents morpholine; -NHC(O)-C6-aryl, Z1-Z-Z2The-D and-C(O)-N(R1)-C0-C3alkyl-C6-aryl-O-C6-aryl, wherein each aryl and heteroaryl optionally substituted from 1 to 3 independently selected substituents: -OR1C1-C3alkyl, halogen, -NR1R2and CF3;
where
Z1represents a chemical bond, C1-C3alkyl or C6-aryl;
Z is a chemical bond, -O-, -N(R1)- ,- N(R1)C(O)O - or-OC(O)N(R1)-;
Z2represents a chemical bond or a C1-C3alkyl;
D represents H, C6-aryl or heterocyclyl representing morpholinyl; and
each of Rcand Rdindependently represents H or-C(O)R1;
provided that Formula (I) excluded the following connections:
N-hydroxy-4-(naphthalen-1-yl)furan-3-carboxamide, N-hydroxy-4-(naphthalen-2-yl)-1H-pyrrol-3-carboxamide, N-hydroxy-4-(naphthalen-1-yl)thiophene-3-carboxamide, N-hydroxy-4-(naphthalen-2-hiltion-3-carboxamide, 5-(3,4-acid)-N-hydroxyquinol-2-carboxamide, and provided that Formula (I) excludes compounds having formula
Rrand Rsindependently represent H, lower halogenated, -CO2H-NO2lowest alkylcarboxylic, lower alkoxygroup or-CN.

2. The compound according to claim 1, having the Formula (Ia)

3. The compound according to claim 1, wherein W representswhere * represents the place of connection to the group of L.

4. The compound according to claim 1, characterized in that n is equal to 0.

5. The compound according to claim 1, wherein L represents an aryl or heteroaryl, where each is optionally substituted 1, 2 or 3 independently selected substituents; OR1C1-C3alkyl, halogen, -NR1R2or CF3.

6. The compound according to claim 1, wherein Y is chosen from the group comprising H, C6-aryl, -C1-C4alkyl, heterocyclyl representing piperidinyl; heteroaryl representing thienyl or benzothiophene; -C0-C3alkyl-C6-aryl, -C0-C3alkyl-heteroaryl where heteroaryl is thienyl; -C6-aryl-heterocyclyl where heterocyclyl choose from indolyl and morpholinyl; -heterocyclyl-C0-C3alkyl-C6-aryl, the de heterocyclyl is piperidinyl; heterocyclyl-C1-C4alkyl-heteroaryl where heterocyclyl is piperidinyl and heteroaryl represents pyridinyl; -heterocyclyl-C(O)-C6-aryl, -CH(C6-aryl)2, -heterocyclyl-C(O)-C1-C4alkyl, -heterocyclyl-C(O)-heterocyclyl where heterocyclyl choose from pyrrolidinyl and piperidinyl; -heterocyclyl-C(O)-O-C1-C3alkyl, -heterocyclyl-SO2-C1-C3alkyl, where heterocyclyl is piperidinyl; -heterocyclyl-SO2-C6-aryl, where heterocyclyl is piperidinyl; -heterocyclyl-C1-C4alkyl-heteroaryl where heterocyclyl is piperidinyl and heteroaryl represents pyridinyl; -heterocyclyl-SO2-C6-aryl-M(H1) -C(O)-C1-C3alkyl, -C1-C3alkyl-O-C6-aryl, -C1-C3alkyl-O-C(O)-N(R1)-C1-C3alkyl-C6-aryl, -C(O)-N(R1)-C6-aryl, -N(R1)-SO2-C1-C3alkyl-C6-aryl, -N(R1)-SO2-C6-aryl, and-N(R1)-SO2-heteroaryl where heteroaryl is thienyl;
where each aryl, heteroaryl and heterocyclyl optionally substituted from 1 to 3 independently selected substituents: -OR1C1-C3alkyl, halogen, -NR1R2and CF3.

7. The compound according to claim 1, characterized in that h is about represents a
,,,,,,
or
M is-C(O)NHOH;
n = 1;
R represents H;
L represents a C6-aryl or-N(R1)SO2-C6-aryl;
Y represents a C6-aryl, C1-C4alkyl, heteroaryl representing thienyl, benzothiophene or piperidinyl; and R1represents H;
whererepresents the place of attachment to group M, * represents the place of attachment to the group L and ** represents a place of connection to the group of U.

8. The compound according to claim 1, characterized in that
is thienyl, thiazolyl, pyrazolyl or oxazolyl;
M is-C(O)NHOH;
L represents a phenyl, thienyl or pyridine, where each is optionally substituted; and
Y represents-Z1-Z-Z2D;
where
Z1represents a chemical bond, C1-C3alkyl or C6-aryl;
Z is a chemical bond, -O-, -NR1-, -NR1C(O)O - or-OC(O)NR1-;
Z2represents a chemical bond or a C1-C3 alkyl; and
D represents H, C6-aryl or heterocyclyl representing morpholinyl.

9. The compound according to claim 1, characterized in that
is thienyl, benzofuranyl, benzothiazol, thiazolyl, pyrazolyl or oxazolyl;
M is-C(O)NHOH;
L represents a phenyl, thienyl or pyridine, each of which is optionally substituted; and
Y represents-Z1-Z-Z2D;
where
Z1represents a chemical bond,
Z represents-O-, -NR1-, -NR1C(O)O - or-OC(O)NR1-;
Z2represents a chemical bond, C1-C3alkyl;
D represents H, C6-aryl, heterocyclyl representing morpholinyl.

10. The compound according to claim 1, having the Formula (In)

where
L represents an optionally substituted aryl; and
Y represents a C6-aryl, -C0-C3alkyl-aryl or heteroaryl where these aryl and heteroaryl are optionally substituted from 1 to 3 independently selected substituents: -OR1C1-C3alkyl, halogen, -NR1R2and CF3.

11. The compound according to claim 1, having the Formula (Iq)

where
L represents an optionally substituted aryl; and
Y is chosen from the group comprising C6 -aryl, -C6-aryl-heterocyclyl where heterocyclyl choose from indolyl and morpholinyl; heteroaryl representing thienyl or benzothiophene; -heterocyclyl-C0-C3alkyl-C6-aryl, where heterocyclyl is piperidinyl; -C0-C3alkyl-heterocyclyl where heterocyclyl is dibenzazepine or dihydrobenzofuranyl; -heterocyclyl-C(O)O-C0-C3alkyl, where heterocyclyl is piperidinyl; heterocyclyl-S(O)2-C0-C3alkyl, where heterocyclyl is piperidinyl; -heterocyclyl-S(O)2-C0-C3alkyl-C6-aryl, where heterocyclyl is piperidinyl; -heterocyclyl-C1-C4alkyl-heteroaryl where heterocyclyl is piperidinyl and heteroaryl represents pyridinyl or indolyl; heterocyclyl-C(O)-C0-C3alkyl-C6-aryl, where heterocyclyl is piperidinyl; -heterocyclyl-C(O)-C1-C4alkyl, where heterocyclyl is piperidinyl; and-CH(C6-aryl)2where each aryl, heterocyclyl and heteroaryl optionally substituted 1-3 independently selected substituents: -OR1C1-C3alkyl, halogen, -NR1R2and CF3.

12. The compound according to claim 1, having the Formula (Iv)

where
L before the hat is optionally substituted phenyl;
Y represents a C6-aryl, -alkyl-O-C6-aryl, -C0-C3alkyl-C6-aryl, -C1-C3alkyl-O-C(O)-N(R1)-C1-C3alkyl-C6-aryl and-C(O)-N(R1)-C6-aryl, where each aryl fragment is optionally substituted 1-3 independently selected substituents: -OR1C1-C3alkyl, halogen, -NR12and CF3;
R1represents-H, -C1-C3alkyl, -C6-aryl or-C1-C3alkyl-C6-aryl.

13. The compound of Formula (II)

and its N-oxides and pharmaceutically acceptable salts, where L2selected from the group comprising H, -C0-C3alkyl-C6-aryl, -C0-C3alkyl-heteroaryl where heteroaryl represents pyridyl; -C1-C6alkyl, wherein each aryl and heteroaryl optionally substituted one, two or three substituents, independently selected from halogen, CF3and OCH3;
Y and M are defined in claim 1.

14. Pharmaceutical composition having inhibitory activity against discontiuation (HDAC) - containing compound according to any one of claims 1 to 13, and a pharmaceutically acceptable carrier.

15. A method of inhibiting the activity discontiuation (HDAC), comprising contacting HDAC or cells containing HDAC, with an effective inhibiting amount of a compound is of any one of claims 1 to 13 or a composition according to 14.

16. The method according to item 15, wherein the HDAC represents one or more of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, and HDAC11.

17. A method of treating diseases that are sensitive to the inhibitor of HDAC activity, including introduction to the needy in the specified treatment to the individual an effective amount of a compound according to any one of claims 1 to 13 or a composition according to 14.

18. The method according to 17, wherein the disease is sensitive to the inhibitor of one or more of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9, and HDAC11.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new benzodiazepine compounds of general formula , wherein each R1, R2, R3 and R4 independently represent hydrogen or alkyl, or R2 and R3 together represent lower alkylene; A1 is lower alkylene optionally substituted by hydroxy; and R5 is a fragment of formula , wherein each R6 and R7 independently represents hydrogen, lower alkyl, cycloalkyl, phenyl, furyl, thienyl, pyrazolyl, etc.; each XA and XB independently represents a bond, lower alkylene, -CO-, -SO2- etc., a pharmaceutical composition containing them, and using the above compound as the pharmaceutical composition or for preparing the same.

EFFECT: new compounds may be used for preventing and treating cardiac arrhythmia.

8 cl, 1047 ex, 78 tbl

Iap inhibitors // 2491276

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula: U1-M-U2, where U1 and U2 have general formula (I), where: G stands for: IVb IVd ive, and values M, X1, X2, R2, R3, R3', R4, R4', R5, R5', R6, R6', R7, Z7, Z2, Z3, Z4, Q2 are given in item 1 of the formula.

EFFECT: compounds can be applied for induction of apoptosis in cell.

37 cl, 13 dwg, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) or pharmaceutically acceptable salts thereof wherein A, R1, R2, R3 and m are specified in the patent claim. The present invention also refers to the number of specific compounds, and to a pharmaceutical composition containing the above compounds effective for inhibition of kinases, such as glycogen synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

EFFECT: preparing the specific compounds and pharmaceutical composition containing the above compounds effective for kinase inhibition.

18 cl, 393 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula (I) and salts thereof wherein R1 represents -A11-A12-; R2 represents tetrahydrofurylmethyl, tetrahydropyranylmethyl or tetrahydropyranyl; A11 represents a single bond, methylene or 3,2-ethylene; A12 represents C1-6 alkyl, C3-6 cycloalkyl or C3-6 cycloalkyl containing methyl; R3 represents methoxy, cyano, cyclobutyloxymethyl, methoxymethyl or ethoxymethyl; and R4 represents methoxy or chlorine. Also, the invention also refers to a pharmaceutical composition possessing corticotrophin-releasing factor (CRF) receptor antagonist activity, containing a compound of formula (I), to a therapeutic/preventive agent, and a method of treating the diseases specified in the patent claim.

EFFECT: there are presented the compounds of formula (I) as corticotropin-releasing factor (CRF) receptor antagonists.

20 cl, 2 dwg, 2 tbl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula 1 , where X and T are N or C, Q is a (3-7)-member aromatic ring which contains 0-3 nitrogen atoms as ring members, and which is optionally benzo-condensed and is substituted with oxo; C1-C6-alkyl; halogen- C1-C6-alkyl; hydroxy-C1-C6-alkyl; C1-C6-alkoxy; C6-C10-aryl; or a (3-7)-member heteroaryl containing 1-3 oxygen atoms, P is C1-C6-alkyl, optionally substituted with a halogen, and R is a group selected from: (i) -C1-C6-alkyl-R1, (ii) -NR2R3, (iii) -O-R4, (iv) -S-R5, (v) -C (=O))-R6, (vi) optionally substituted (3-7)-member heteroaryl containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vi) optionally substituted (3-7)-member heteroatom containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (vii) optionally substituted, saturated or partially unsaturated, separate or condensed (3-10)-member heterocyclic ring containing 1-4 heteroatoms selected from a nitrogen atom, an oxygen atom and a sulphur atom, (viii) azido; where each R1, R2, R3, R4, R3, R6, is as described in the claim. The invention also relates to a pharmaceutical composition for preventing and treating a vascular disease, which contains a compound of formula 1.

EFFECT: compounds of formula 1 with inhibitory activity with reference to aggregation of thrombocytes.

7 cl, 7 dwg, 2 tbl, 519 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a 2-aza-bicyclo[3.3.0]octane derivative of formula , with stereogenic centres in a (1S,3S,5S)-configuration, where A is a thiazolyl which is unsubstituted or monosubstituted, where the substitute is independently selected from a group comprising C1-4alkyl, C3-6cycloalkyl and NH2; B is phenyl which is unsubstituted or mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, trifluoromethyl, NHC(O)CH3 and halogen; and R1 is an imidazo[2,1·b]thiazolyl or benzoisoxazolyl group, where said groups are independently unsubstituted or monosubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl; or R1 is a 2,3-dihydrobenzofuranyl group; or a pharmaceutically acceptable salt. The 2-aza-bicyclo[3.3.0]octane derivative of formula (I) is as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: obtaining novel 2-aza-bicyclo[3,3,0]octane derivatives as orexin receptor antagonists.

8 cl, 1 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of general formula:

or its pharmaceutically acceptable salt wherein the ring A represents a phenyl group which can contain 1-3 substitutes specified in a group of substitutes, or a thienyl group which can contain 1-3 substitutes specified in a group of substitutes α; L represents a single bond or a group of formula -NRC CO- (wherein Re represents a hydrogen atom), the ring B represents C6-14 aryl group which can contain 1-3 substitutes specified in a group of substitutes α, or a 5-10-member heterocyclic group which can contain 1-3 substitutes specified in a group of substitutes α; the X, Y, Z , R1 and R2 , R3, R4, R5 and R6 radical values are presented in cl.1 of the patent claim which possess an effect of Aβ protein production inhibition or an effect of BACE1 inhibition.

EFFECT: preparing the compound which is applicable as a preventive or therapeutic agent for neurodegenerative disease caused by Aβ.

13 cl, 35 tbl, 285 ex

FIELD: chemistry.

SUBSTANCE: invention relates to bicyclosulphonyl acid (BCSA) compounds of formula: where: where each of -Rpw, -Rpx, -RPY, and -RPZ independently denotes H or -RRS1; each -RRS1 independently denotes -F, -Cl, -Br, -I, -RA1, -CF3, -OH, -OCF3 or -ORA1; where each RA1 independently denotes C1-4alkyl, phenyl or benzyl; and additionally, two neighbouring -RRS1 groups can together form -OCH2O-, -OCH2CH2O- or -OCH2CH2CH2O-; -RAK independently denotes a covalent bond, -(CH2)- or -(CH2)2-; -RN independently denotes -RNNN, or -LN-RNNN; the rest of the values of the radicals are given in claim 1, which act as inhibitors of inhibitors of tumor necrosis factor-α converting enzyme (TACE).

EFFECT: compounds are useful in treating TNF-α mediated conditions.

36 cl, 303 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-aza-bicyclo[3.3.0]octane derivatives of formula , where R1 and R2 are hydrogen, C1-4alkyl or fluorine; R3 is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl, trifluoromethoxy group and halogen; 2,3-dihydrobenzofuranyl; 2,3-dihydrobenzo[1,4]dioxynyl; or isoxazolyl, pyridyl, indazolyl, benzofuranyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, pyrrolo[2,1b]thiazolyl, imidazo[ 1,2-a]pyridinyl or imidazo[2,1-b]thiazolyl, where said groups are unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, halogen and trifluoromethyl; A is or ; R4 is C1-4alkyl or -NR6R7; R6 is hydrogen or C1-4alkyl; R7 is hydrogen or C1-4alkyl; and D is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl and halogen; or a pharmaceutically acceptable salt of such a compound. 3-aza-bicyclo[3.3.0]octane derivatives or a pharmaceutically acceptable salt thereof are used as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: novel 3-aza-bicyclo[3,3,0]octane derivatives as nonpeptide antagonists of human orexin receptors.

9 cl, 1 tbl, 85 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new antibacterial compounds of formula I

wherein R1 represents halogen or alkoxy group; each U and W represents N; V represents CH, and R2 represents H or F, or each U and V represents CH; W represents N, and R2 represents H or F, or U represents N; V represents CH; W represents CH or CRa, and R2 represents H, or also when W represents CH, may represent F; Ra represents CH2OH or alkoxycarbonyl; A represents group CH=CH-B, a binuclear heterocyclic system D, phenyl group which is mono-substituted in the position 4 by C1-4 alkyl group, or phenyl group which is di-substituted in positions 3 and 4 wherein each of two substitutes is optionally specified in a group consisting of C1-4 alkyl and halogen; B represents mono- or di-substituted phenyl group wherein each substitute is a halogen atom; D represents group

wherein Z represents CH or N, and Q represents O or S; or to salts of such compounds.

EFFECT: compounds are used for treating bacterial infections.

13 cl, 2 tbl, 25 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyridin-2-one and pyridazin-3-one derivatives, having Btk inhibiting activity. In formulae I-IV:

,

R denotes -R1-R2-R3 or -R2-R3; R1 denotes a heteroaryl containing 6 ring atoms, including one N heteroatom; R2 denotes -C(=O), -C(=O)N(R2'), where R2' denotes H; R3 denotes R4; where R4 is a lower alkyl, heterocycloalkyl, (lower alkyl) heterocycloalkyl or heterocycloalkyl (lower alkyl), where the heterocycloalkyl contains 6 ring atoms, including two heteroatoms selected from N and O; and where R4 can be substituted with one or more substitutes selected from lower alkyl, oxo group and lower alkoxy group; X denotes CH or N; Y1 denotes lower alkyl; n and m are equal to 0; values of radicals Y2, Y4 are given in the claim.

EFFECT: improved properties of compounds.

6 cl, 2 tbl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or a pharmaceutically acceptable salt thereof, wherein G1 is phenyl or pyridyl, each of which is optionally additionally substituted by one substitute presented by T; G2 is phenyl, 1,3-thiazolyl or 1,3-oxazolyl, wherein G2 is bound to G1 in the para position in relation to a place of attachment of G1 to group NH in formula (I), wherein G2 means phenyl, G3 is bound to G2 in the para position of G2 in relation to G1, and wherein provided G2 represents 1,3-thiazolyl or 1,3-oxazolyl, G2 is bound to G1 in the position of 5 G2 and G3 is bound to G2 in the position of 2 G2; T in each case is independently specified in a group containing C1-6alkyl and halogen; G3 is presented by formula or by formula ; W1 is -C(R3)(R4)-C(R3)(R4)-, and W2 represents N; or W3 represents O; W4 is -C(R3)(R4) -; each R3 and R4 is hydrogen; each R5 and R6 kis hydrogen; Rc and Rd together with a carbon atom whereto attached, are a 4-5-member cycloalkyl or monocyclic heterocycle of formula ; wherein one hydrogen atoms attached to the carbon atom of the cycloalkyl ring and monocyclic heterocycle is optionally substituted by a radical specified in a group -C(O)O(R8); W5 is -CH2- or -CH2-CH2-; W6 is O or N(RX), wherein Rx is hydrogen, C1-6alkyl or -C(O)O(Rz); RZ in each case is independently C1-6alkyl; R8 is hydrogen; L1 is O; and X is hydrogen, C1-6alkyl, or - (CRgRh)u-C(O)O(R10); or L1 is -CH2- and X is -C(O)OH; R10 is hydrogen; or Q is G4 or Y1-Y3; or Q is described for formula wherein Z is phenyl; G4 is benzothiazole or benzoxazole optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of C1-6alkyl, halogen and -OR1; Y1 in each case is independently -C(O)-, -C(O)O- or -C(O)N(Rw)-, wherein the right side -C(O)O- and -C(O)N(Rw)- of the groups is attached to Y3 or (CRJRk)v, Y3 in each case is independently phenyl, benzyl, piperidinyl or bicyclo[4.2.0]octa-1,3,5-triene, wherein the phenyl and benzyl residues are optionally additionally substituted by 1 or 2 substitutes specified in a group consisting of halogen and haloC1-6alkyl; Rg and Rh in each case is independently hydrogen, or C1-6alkyl; R1 in each case is independently halogenC1-6alkyl; Rw is hydrogen; and u means 1.

EFFECT: compounds being the type 1 diacylglycerol O-acyltransferase (DGAT-1) enzyme inhibitors.

7 cl, 1 tbl, 61 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new benzodiazepine compounds of general formula , wherein each R1, R2, R3 and R4 independently represent hydrogen or alkyl, or R2 and R3 together represent lower alkylene; A1 is lower alkylene optionally substituted by hydroxy; and R5 is a fragment of formula , wherein each R6 and R7 independently represents hydrogen, lower alkyl, cycloalkyl, phenyl, furyl, thienyl, pyrazolyl, etc.; each XA and XB independently represents a bond, lower alkylene, -CO-, -SO2- etc., a pharmaceutical composition containing them, and using the above compound as the pharmaceutical composition or for preparing the same.

EFFECT: new compounds may be used for preventing and treating cardiac arrhythmia.

8 cl, 1047 ex, 78 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds being aspartyl protease inhibitors applicable for treating cardiovascular, neurodegenerative disorders and fungal infection of formula , wherein W represents -C(=O)-; X represents -NH-; U represents -C(R6)(R7)-; R1 represents methyl, R2, R3 and R6 represent H, R4 and R7 represent optionally substituted phenyl, as well as tautomers and pharmaceutically acceptable salts thereof.

EFFECT: there are presented new effective aspartyl protease inhibitors specified in rennin, cathepsin D, BACE-1, for treating cardiovascular diseases, cognitive and neurodegenerative diseases, as well as fungal infections.

67 cl, 1 tbl, 4393 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to indolyl-substituted derivatives of thiadiazinones prepared from oxamic acid thiohydrazide of general formula: , wherein R represents H; R1 represents pyridinyl; phenyl substituted by alkyl C1-C5, Hal, CF3; R2 represents H; alkyl C1-C5; -CH2COOR4; benzyl substituted by Hal, OR4; benzoyl substituted by Hal, OR4, while R4 represents unsubstituted alkyl C1-C4.

EFFECT: there are prepared new compound which can find application in medicine for developing the therapeutic agent possessing pathogenic bacteria inhibitory activity.

2 cl, 2 dwg, 2 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel heterocyclic nitrogen- and oxygen-containing compounds having insecticidal activity. In formulae (A) (B) (C) (D) R1 is a 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/ or sulphur atom, a halogen-substituted 5- or 6-member heterocyclic ring containing a nitrogen, oxygen and/or sulphur atom, a substituted or unsubstituted phenyl, where the substitutes are one or more groups selected from a group consisting of halogen atoms, C1-4 halogen alkyl or C1-4 chloroalkoxyl; R5, R6, R7, R8 and R9 are H, saturated or unsaturated C1-4 alkyl, halogen atom, saturated or unsaturated C1-4 alkoxyl, saturated C1-4 halogenalkoxyl, C1-4 alkylcarbonyl, C1-8 alkyl ester, C1-4 alkylsulphonyl, phenyl, benzyl or trifluoromethane sulphonyl ether group; Y is nitro, cyano, trifluoromethyl, trifluoroacetyl or trifluoromethylsuphonyl. Values of radicals R, R2-R4 are given in the claim.

EFFECT: invention also relates to an agrochemical composition containing said compounds, use of the agrochemical composition in pest control and a method of producing said compounds.

12 cl, 7 tbl, 36 ex

Azole compounds // 2493154

FIELD: chemistry.

SUBSTANCE: invention relates to compounds which are pyridin-3-yl 4-(3-phenyl-1H-1,2,4-triazol-5-yl)piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-[3-(4-fluoromethyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-[5-(4-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate, 2,6-dimethylpyridin-3-yl 4-[5-(3,4-difluorophenyl)-1,2,4-oxadiazol-3-yl]piperidine-1-carboxylate, 2-methylpyridin-3-yl 4-[3-(2-fluorophenyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate, 6-methylpyridin-3-yl 4-(3-phenyl-1H-pyrazol-1-yl)piperidine-1-carboxylate, 2-methylpyridin-3-yl 4-[5-(3-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate and 6-methylpyridin-3-yl 4-[4-(4-fluorophenyl)-1,3-oxazol-2-yl]piperidine-1-carboxylate or to a pharmaceutically acceptable salt thereof. The invention also relates to a pharmaceutical composition based on said compounds, having inhibiting effect on fatty acid amide hydrolase (FAAH).

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine for treating neuropathic pain.

13 cl, 38 tbl, 159 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound, which is N3-1H-indol-5-yl-5-pyridin-4-ylpyrazine-2,3-diamine, or a pharmaceutically acceptable salt thereof, which can act as inhibitors of protein kinase, especially FLT3 tyrosine kinase. The invention also relates to a pharmaceutical composition which contains said compound in combination with another molecularly directed (target) agent, which is a traditional cytotoxic agent or a compound used after chemotherapy, supporting therapy targeted on stem cells and in case of MLL rearrangement acute lymphoblastic leukaemia in children.

EFFECT: obtaining a novel compound which can be used in medicine for preventing or treating haematological malignant growths such as AML, MLL, T-ALL, B-ALL and CMML, myeloproliferative diseases, autoimmune diseases and skin diseases, such as psoriasis and atopic dermatitis.

16 cl, 2 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to antibacterial compounds of formula (I) , where one or two of U, V, W and X represent N, the remaining ones represent CH or, in case X, can also represent CRa, where Ra represents fluorine; R1 represents alcoxygroup, halogen or cyanogroup; R2 represents H, CH2OH, CH2N3, CH2NH2, alkylcarbonylaminomethyl or triazol-1-ylmethyl; R3 represents H or, when n=1, R3 can also represent OH, NH2, NHCOR6 or triazol-1-yl; A represents CR4; K represents O, NH, OCH2, NHCO, NHCH2; CH2NH5 CH2CH2, CH=CH, CHOHCHOH or CHR5; R3 represents H or together with R5 forms bond, or R4 can also represent OH, when K is not O, NH, OCH2 or NHCO; R5 represents OH or together with R4 forms bond; R6 represents alkyl; m=0 or 1 and n=0 or 1; and G is specified in i.1 of the formula; and to salt of such compound.

EFFECT: obtaining antibacterial compounds.

19 cl, 1 tbl, 44 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel pyridine derivatives pyridine1-A-pyridine2 of formula (1), where pyridine1 represents

, , or , ,

where asterisks stand for bond, which contains pyridine1 ring with A; R1 represents C1-5alkyl, C1-4alkoxygroup, C3-6-cycloalkyl, hydroxymethyl or NR1aR1b, R1a represents C1-4alkyl; R1b represents hydrogen or C1-3alkyl; or R1a and R1b, together with nitrogen atom, which is bound to pyridine, form pyrrolidine ring; R2 represents hydrogen or C1-4alkyl, or in case, when R1 represents C1-5alkyl or C3-6-cycloalkyl, R2 can additionally represent methoxygroup; R3 represents C1-4alkyl, C1-4alkoxygroup, C3-6-cycloalkyl or NR3aR3b; R3a represents C1-4alkyl; R3b represents hydrogen or C1-3alkyl; R4 represents C1-4alkyl or hydrogen; R5 represents C1-5alkyl, methoxygroup or NR5aR5b; and R6 represents C1-2alkyl; R5a represents C1-4alkyl; R5 represents hydrogen or C1-3alkyl; or R5 represents C1-2alkyl or methoxygroup; and R6 represents C1-5alkyl or NR6aR6b; R6a represents C1-4alkyl; R6b represents hydrogen or C1-3alkyl; R7 represents C1-5alkyl; R8 represents C1-2alkyl or methoxygroup; R9 represents C1-5alkyl; R10 represents C1-2alkyl; A represents

, , or ,

where asterisks stand for bond, binding pyridine1 ring with A; pyridine2 represents

, , or , ,

where asterisks stand for bond, which binds pyridine ring with A; R11 represents C1-4alkyl; C1-3alkyloxy group, hydroxymethyl or NR11aR11b; R,1a represents C1-3alkyl; R11b represents hydrogen or C1-2alkyl; R12 represents hydrogen or C1-4alkyl; R13 represents C1-4alkyl or NR13aR13b; R13a represents C1-4alkyl; R13b represents hydrogen or C1-2alkyl; R14 represents C1-2alkyl; R15 represents C1-4alkyl or NR15aR15b; and R16 represents C1-2alkyl; R15a represents C1-3alkyl; R15b represents hydrogen or C1-3alkyl; or R15 represents C1-2alkyl; and R16 represents C1-4alkyl or NR16aR16b; R16a represents C1-3alkyl; R16b represents hydrogen or C1-2alkyl; R17 represents C1-4alkyl; R18 represents C1-2alkyl or methoxygroup; R19 represents C1-4alkyl; and R20 represents C1-2alkyl; with exception of 3-(2-ethyl-4-pyridyl)-5-(2-ethyl-4-pyridyl)-1,2,4-oxadiazole; or pharmaceutically acceptable salt of such compound.

EFFECT: obtaining pyridine derivatives, which possess agonistic activity with respect to S1P1/EDG1.

15 cl, 2 tbl, 131 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel phenylaminopyrimidine compounds of formula I, which are JAK kinase inhibitors. In particular, these compounds selectively act on JAK2 kinase. The compounds can be used to treat diseases such as immunological and inflammatory diseases; hyperproliferative diseases, myeloproliferative diseases; viral diseases; metabolic diseases; and vascular diseases. In the compound of formula I , Q and Z are independently selected from N and CR1; R1 is independently selected from hydrogen, halogen, R2, OR2, OH, R4, OR4, CN, CF3, (CH2)nN(R2)2, where n equals 1,2 or 3, NO2, R2R4, NR2SO2R3, COR4, NR2COR3, CO2H, CO2R2, NR2COR4, R2CN, R2OH, R2OR3 and OR5R4; or two substitutes R1 together with carbon atoms with which they are bonded form an unsaturated 5- or 6-member heterocyclic ring containing 1-4 N atoms; R2 is C1-4alkyl; R4 is R2, C2-4alkenyl or phenyl; R4 is NH2, NHR2, N(R1)2, substituted or unsubstituted morpholine, CH2morpholine, substituted or unsubstituted thiomorpholine, substituted or unsubstituted thiomorpholino-1-oxide, substituted or unsubstituted thiomorpholino-1,1-dioxide, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted imidazolyl, substituted or tetrahydrofuranyl unsubstituted and substituted or unsubstituted tetrahydropyranyl; R5 is C2-4alkylene; R6-R9 are independently selected from H, RXCN, halogen, substituted or unsubstituted C1-4alkyl, OR1, CO2R1, N(R1)2, NO2 and CON(R1)2, wherein at least one of R6-R9 is RXCN; the rest of the values of the radicals are given in the claim.

EFFECT: high efficiency of treatment.

29 cl, 7 dwg, 2 tbl, 93 ex

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