2-imidazobenzothiazoles as ligands of adenosine receptor

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

 

The text descriptions are given in facsimile form.

1. Compounds of General formula

,

in which R1denotes phenyl or 5-6-membered heterocycle containing one N atom and/or one atom Of;

R2denotes an imidazole or annelirovannymi an imidazole selected from the group including

,,

and,

R3denotes hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophene-3-yl, 3-methylbenzo[b]thiophene-2-yl, thiophene-2-yl, thiophene-3-yl or type the-2-ylmethyl,

R4denotes hydrogen or lower alkyl;

R5denotes hydrogen, lower alkyl, halogen, morpholinyl, -NR'r R", piperidinyl, optionally substituted by a hydroxy-group, or denotes pyrrolidin-1-yl;

R6denotes hydrogen or -(CH2)nO-lower alkyl,

R7denotes hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'r R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridine-4-yl ring which may contain as substituents of lower alkyl,

halogen-lower alkyl or pyrrolidin-1-ylmethyl, or represents -(CH2)n-C(O)-NR'r R";

R'/R" independently of one another denote hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl,

X denotes-CH2-, -NR'- or-O-;

R"' denotes hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3or benzyl;

n is 1 or 2;

and their pharmaceutically acceptable salts joining with acids.

2. The compounds of formula Ia according to claim 1

in which R1denotes phenyl or 5-6-membered heterocyclyl containing one N atom and/or one atom of O, and

R3 denotes hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophene-3-yl, 3-methylbenzo[b]thiophene-2-yl, thiophene-2-yl, thiophene-3-yl

or thiophene-2-ylmethyl,

and their pharmaceutically acceptable salts joining with acids.

3. The compounds of formula Ib according to claim 1,

in which R1denotes phenyl or 5-6-membered heterocyclyl containing one N atom and/or one atom of O, and

R4denotes hydrogen or lower alkyl,

and their pharmaceutically acceptable salts joining with acids.

4. The compounds of formula 1C according to claim 1,

in which R1denotes phenyl or 5-6-membered heterocyclyl containing one N atom and/or one atom Of;

R5denotes hydrogen, lower alkyl, halogen, morpholinyl, -NR'r R", piperidinyl, optionally substituted by a hydroxy-group, or denotes pyrrolidin-1-yl;

R6denotes hydrogen or -(CH2)nO-lower alkyl,

and their pharmaceutically acceptable salts joining with acids.

5. The compounds of formula Id according to claim 1,

in which R1denotes phenyl or 5-6-membered heterocyclyl containing one N atom and/or one atom Of;

X denotes-CH2-, -NR'-or-O-;

R"' denotes water is od -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3or benzyl;

and their pharmaceutically acceptable salts joining with acids.

6. The compounds of formula 1 according to claim 1,

in which R1denotes phenyl or 5-6-membered heterocyclyl containing one N atom and/or one atom Of;

R7denotes hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'r R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridine-4-yl ring which may contain as substituents of lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl, or represents -(CH2)n-C(O)-NR'r R";

R'/R" independently of one another denote hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl,

and their pharmaceutically acceptable salts joining with acids.

7. The compounds of formula I according to claim 1, in which R1denotes morpholinyl.

8. The compounds of formula 1A according to claim 2, represented by the following compounds:

2-(1H-imidazol-2-yl)-4-methoxy-7-morpholine-4-eventhorizon,

2-(1H-imidazol-2-yl)-4-methoxy-7-phenylbenzothiazole,

4-methoxy-7-morpholine-4-yl-2-(4-phenyl-1H-imidazol-2-yl)-benzothiazole,

2-[4-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-1H-imidazol-2-yl]-4-methoxy-7-morpholine-4-eventhorizon,

2-(5-benzo[b]thiophene-3-yl-1H-imidazol-2-yl)-4-methoxy-7-morpholine-4-eventhorizon,

4-methoxy-7-morpholine-4-yl-2-(4-thiophene-2-yl-1H-imidazol-2-yl)-benzothiazole,

4-methoxy-7-morpholine-4-yl-2-(4-thiophene-3-yl-1H-imidazol-2-yl)-benzothiazole

or

4-methoxy-7-morpholine-4-yl-2-(4-thiophene-2-ylmethyl-1H-imidazol-2-yl)-benzothiazole.

9. The compounds of formula Ib according to claim 3, represented by the following compounds:

2-(1H-benzimidazole-2-yl)-4-methoxy-7-morpholine-4-eventhorizon or 4-methoxy-2-(1-methyl-1H-benzimidazole-2-yl)-7-morpholine-4-eventhorizon.

10. The compounds of formula 1C according to claim 4, represented by the following compounds:

2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-5-methyl-3H-imidazo[4,5-b]pyridine,

5-chloro-2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3H-imidazo[4,5-b]pyridine,

5-chloro-3-methoxymethyl-2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3H-imidazo[4,5-b]pyridine,

3-methoxymethyl-2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-5-morpholine-4-yl-3H-imidazo[4,5-b]pyridine,

2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-5-morpholine-4-yl-3H-imidazo[4,5-b]pyridine,

3-methoxymethyl-2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-5-pyrrolidin-1-yl-3H-imidazo[4,5-b]pyridine,

2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-5-pyrrolidin-1 and is-3H-imidazo[4,5-b]pyridine,

[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3H-imidazo[4,5-b]pyridine-5-yl]-dimethylamine,

1-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3H-imidazo[4,5-b]pyridine-5-yl]-piperidine-4-yl or

[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3H-imidazo[4,5-b]pyridine-5-yl]-methyl-(tetrahydropyran-4-ylmethyl)-amine.

11. The compounds of formula Id according to claim 5, represented by the following compounds:

4-methoxy-7-morpholine-4-yl-2-(4,5,6,7-tetrahydro-1H-benzimidazole-2-yl)-benzothiazole,

2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3,4,6,7-tetrahydropyrido[3,4-4]imidazole,

tert-butyl ester 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-3,4,6,7-tetrahydroimidazo[4,5-C]pyridine-5-carboxylic acid,

hydrochloride of 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-C]pyridine,

[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-C]pyridine-5-yl]-o-trimeton,

1-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-C]pyridine-5-yl]-alanon or

ethyl ester of 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-1,4,6,7-tetrahydroimidazo[4,5-C]pyridine-5-carboxylic acid.

12. The compounds of formula 1 according to claim 6, represented by the following compounds:

tert-butyl ester 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-carboxylic acid is you,

hydrochloride of 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-1,4,5,6,7,8-hexahydrobenzo[4,5-d]azepine,

(4-forfinal)-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl]-methanon,

1-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl]-ethanol,

[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl]-o-trimeton,

1-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl]-2,2-DIMETHYLPROPANE-1-he,

cyclopropyl-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-4]azepin-6-yl]-methanon,

dimethylamide 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-carboxylic acid,

2-methoxy-1-[2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-yl]-Etalon,

ethyl ester of 2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-4,5,7,8-tetrahydro-1H-imidazo[4,5-d]azepin-6-carboxylic acid,

6-methanesulfonyl-2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-1,4,5,6,7,8-hexahydrobenzo[4,5-d]azepin or

6-(2-methoxyethyl)-2-(4-methoxy-7-morpholine-4-eventhorizon-2-yl)-1,4,5,6,7,8-hexahydrobenzo[4,5-d]azepin.

13. A drug that has affinity to the adenosine receptor And2Aand sat is aktivnosti against adenosine receptor And 1containing one or more compounds according to any one of claims 1 to 12 and a pharmaceutically acceptable inert fillers.

14. The drug is indicated in paragraph 13, intended for treatment of diseases associated with adenosine receptors And2Aand a1.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of formula (I) as well as to synthesis procedure and application for treatment of various disorders, including inflammatory and autoimmune disorders, and disorders caused by malignant growths or by increased angiogenesis where R1-R11, t, X, Y, Z and n have values specified in the description.

EFFECT: production of macrocyclic compounds used for treatment of various disorders, including inflammatory and autoimmune disorders, and disorders caused by malignant growths or by increased angiogenesis.

41 cl, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns new tricyclic derivatives of the formula (I) and their pharmaceutically acceptable salts, where: 1 to 3 of A1, A2, A3 and A4 are nitrogen atoms, while the rest are -CH- groups; G1 is a group selected out of -CH2-O-, -CH2-CH2-, - CH=CH-; -N(C1-C4alkyl)-CH2; G2 is a group selected out of -O-CH2-, -CH=CH-, -CH2- CH2-; R4 can be identical or different and are selected out of a group including hydrogen or halogen atoms; p are independently equal to 0, 1 or 2; Y is and optionally substituted residuum selected out of the group of alkyl, cycloalkyl, alkylaryl, alkylcycloalkylalkyl; Z is a tetrazolyl, -COOR5, -CONR5R5, NHSO2R5 or -CONHSO2R5 group, where R5 is hydrogen or optionally substituted alkyl or aryl. The invention also concerns a method of obtaining the claimed compounds.

EFFECT: possible application in treatment and prophylactics of inflammation and allergy diseases.

20 cl, 2 tbl, 46 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the bonds consistent with the general formula (I) or the general formula (II) where: R1 = H; Z = O or S; P1 = CR5R6, P2 = CR7R8, Q = CR9R10; each of R5, R6, R7, R8, R9 and R10 denotes H; Y = CR12R13-CO, where R12, R13 is selected from C0-7-alkyl; C3-6-cycloalkyl or phenyl-C0-7-alkyl; and where the phenyl ring doesn't have to be substituted R19, specified below; in the group (X)0, X = CRI4R15, where R14 and R15 are independently selected from C0-7-alkyl, and o represents a number from zero to three; (W)n, W = O, S, C(O), S(O) or S(O)2 or NR16, where R16 denotes H, and n equals zero or one; (V)m, V = C(O), NHC(O), C(O)NH or CR17R18, where R17 and R18 denotes H, and m represents a number from zero to three, on condition that, when m is more than one, (V)m contains a maximum of one carbonyl group; U = a stable 5-7-member monocyclic or 8-11-member dicyclic ring, which is saturated or non-saturated and which has from zero to four heteroatoms selected from: , where R19 represents: C0-7-alkyl, C3-6-cycloclkyl, Ar-C0-7-alkyl, O-C0-7-aklyl, NH-C0-7-alkyl, N(C0-7-alkyl)2, O-phenyl, S-phenyl; or, as a part of CHR19 or CR19 group, R19 can represent a halogen; where Ar represents a stable 5- or 6- member monocyclic or stable 9- or 10- member dicyclic ring, which is unsaturated as determined earlier for U, and where Ar doesn't have to be substituted R19, which is of importance specified above; C0-7-alkyl represents a stable linear or a branched aliphatic carbon chain, which contains from 0 to 7 carbon atoms, which doesn't have to be substituted with one, two or three halogen atoms and doesn't have to contain one or few heteroatoms selected from O, N and S, where the heteroatom is present only when C0-7-alkyl contains as a minimum one carbon atom; C3-6-cycloalkyl relates to C0-7-alkyl, certainly higher than the additionally contained carboxyl ring, which doesn't have to be substituted with one or more halogens, selected from F, Cl, Br and I or heteroatoms, selected from N, O, S; A represents O; B, D and G are independently selected from: CR19, where R19 is as specified above or N; E represents O or S; J, L, M, R, T, T2, T3 and T4 which are independently selected from: CR19 and N, where R19 is as specified above; T5 represents N; q represents a number from one to three, determining in this way a 5-, 6- or 7- member ring or its salt, hydrate or solvate. The bonds of the general formula (I) or the general formula (II), represent cruzipain inhibitors and inhibitors of other cisteinproteases and can be used as therapeutic agents, for example, in cases of Chagas disease or for confirmation of target oriented therapeutic bonding.

EFFECT: new bonds which posses helpful biological properties have been discovered.

27 cl, 156 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to the bonds consistent with the general formula (I) or the general formula (II) where: R1 = H; Z = O or S; P1 = CR5R6, P2 = CR7R8, Q = CR9R10; each of R5, R6, R7, R8, R9 and R10 denotes H; Y = CR12R13-CO, where R12, R13 is selected from C0-7-alkyl; C3-6-cycloalkyl or phenyl-C0-7-alkyl; and where the phenyl ring doesn't have to be substituted R19, specified below; in the group (X)0, X = CRI4R15, where R14 and R15 are independently selected from C0-7-alkyl, and o represents a number from zero to three; (W)n, W = O, S, C(O), S(O) or S(O)2 or NR16, where R16 denotes H, and n equals zero or one; (V)m, V = C(O), NHC(O), C(O)NH or CR17R18, where R17 and R18 denotes H, and m represents a number from zero to three, on condition that, when m is more than one, (V)m contains a maximum of one carbonyl group; U = a stable 5-7-member monocyclic or 8-11-member dicyclic ring, which is saturated or non-saturated and which has from zero to four heteroatoms selected from: , where R19 represents: C0-7-alkyl, C3-6-cycloclkyl, Ar-C0-7-alkyl, O-C0-7-aklyl, NH-C0-7-alkyl, N(C0-7-alkyl)2, O-phenyl, S-phenyl; or, as a part of CHR19 or CR19 group, R19 can represent a halogen; where Ar represents a stable 5- or 6- member monocyclic or stable 9- or 10- member dicyclic ring, which is unsaturated as determined earlier for U, and where Ar doesn't have to be substituted R19, which is of importance specified above; C0-7-alkyl represents a stable linear or a branched aliphatic carbon chain, which contains from 0 to 7 carbon atoms, which doesn't have to be substituted with one, two or three halogen atoms and doesn't have to contain one or few heteroatoms selected from O, N and S, where the heteroatom is present only when C0-7-alkyl contains as a minimum one carbon atom; C3-6-cycloalkyl relates to C0-7-alkyl, certainly higher than the additionally contained carboxyl ring, which doesn't have to be substituted with one or more halogens, selected from F, Cl, Br and I or heteroatoms, selected from N, O, S; A represents O; B, D and G are independently selected from: CR19, where R19 is as specified above or N; E represents O or S; J, L, M, R, T, T2, T3 and T4 which are independently selected from: CR19 and N, where R19 is as specified above; T5 represents N; q represents a number from one to three, determining in this way a 5-, 6- or 7- member ring or its salt, hydrate or solvate. The bonds of the general formula (I) or the general formula (II), represent cruzipain inhibitors and inhibitors of other cisteinproteases and can be used as therapeutic agents, for example, in cases of Chagas disease or for confirmation of target oriented therapeutic bonding.

EFFECT: new bonds which posses helpful biological properties have been discovered.

27 cl, 156 ex, 2 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to heterocycle-substituted tricyclic compounds of the formula (I): or their pharmaceutically acceptable salts wherein R means hydrogen atom; R1 and R2 are chosen independently from group comprising hydrogen atom or alkyl comprising 1-6 carbon atoms; R3 means hydrogen atom; n1 and n2 = 0-3 independently under condition that they both do not mean 0; Het means pyridyl wherein pyridyl is added to B through cyclic carbon atom and it comprises from 1 to 4 substitutes (W) chosen independently from group comprising -NR4R5, -NHCOR26, -NHSO2R16; R21 means aryl and R21 means heteroaryl wherein heteroaryl represents furyl, thienyl, pyridyl, thiazolyl, pyrrolidinyl, azethidinyl; R4 and R5 mean hydrogen atom or alkyl comprising 1-6 carbon atoms, or R4 and R5 mean in common -(CH2)3-, -(CH2)4-, -(CH2)5- or -(CH2)2NR7-(CH2)2- wherein R7 means hydrogen atom or alkyl comprising 1-6 carbon atoms; R8, R, R10 and R11 mean hydrogen atom; B means -(CH2)n4CR12=CR12a(CH2)n5 wherein n4 and n5 = 0-2 independently; R12 and R12a are chosen independently from group comprising hydrogen atom or alkyl comprising 1-6 carbon atoms; R21 means from 1 to 3 substitutes chosen independently from group comprising hydrogen atom, trifluoromethyl, trifluoromethoxy, halogen atom, cyano, alkyl comprising 1-6 carbon atoms, alkoxy group comprising 1-6 carbon atoms, or -CR29(=NOR28); R22 means -COR23, -S(O)R31, -S(O)2R31 or -COOR27; R23 means cycloalkyl comprising 3-7 carbon atoms, (C3-C7)-cycloalkyl-(C1-C6)-alkyl, cycloalkyl comprising 3-7 carbon atoms containing from 1 to 3 substitutes chosen from group comprising halogen atom, (C1-C3)-alkoxy-(C1-C3)-alkyl, hydroxy group and alkoxy group comprising 1-6 carbon atoms, aryl, aryl-(C2-C6)-alkyl; R27 means alkyl comprising 1-6 carbon atoms, phenyl or benzyl; R28 and R29 are chosen independently from group comprising hydrogen atom or alkyl comprising 1-6 carbon atoms; R31 means alkyl comprising 1-6 carbon atoms, halogenalkyl comprising 1-6 carbon atoms, aryl, aryl-(C1-C6)-alkyl. Also, invention relates to pharmaceutical compositions containing these substances and their using for preparing a drug used in treatment of thrombosis, atherosclerosis, restenosis, hypertension, stenocardia, arrhythmia, heart failure and cancer.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

10 cl, 11 tbl, 9 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

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

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

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

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

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

35 cl, 16 sch, 13 tbl, 43 ex

FIELD: synthesis of biologically active compounds.

SUBSTANCE: invention provides novel condensed furan compounds of general formula I: , wherein circle X represents benzene, pyridine, or the like; Y optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted piperidyl, oxo-substituted pyrrolydyl, or oxo-substituted morpholino group; R3 hydrogen and the like; and R4 is hydrogen, or a pharmaceutically acceptable salt thereof, which are useful as drugs, especially as inhibitor of activated blood coagulation factor A, as well as intermediate compounds.

EFFECT: expanded synthetic possibilities in furan series and increased choice of biologically active compounds.

16 cl, 85 tbl, 481 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: medicine.

SUBSTANCE: new derivatives of pyrrol[2,1-c][1,4]benzodiazepine of the general formula where n=2-10 are described. A pharmaceutical composition, containing them, and the method of obtaining are also described.

EFFECT: compounds possess antitumoral activity and can be applied in medicine.

18 cl, 3 ex, 2 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention relates to pyperidine derivatives of formula (I) , where R represents galogen or C1-4alkyl; R1 represents C1-4alkyl; R2 or R3 independently represent hydrogen or C1-4alkyl; R4 represents trifluorinemethyl or galogen; R5 represents hydrogen, C1-4alkyl or C3-7cycloalkyl; R6 represents hydrogen, R7 represents radical of formula (W), or R7 represents radical of formula (W) and R7 represents hydrogen; X represents CH2, NR5 or O; Y represents nitrogen, and Z represents nitrogen; or Y represents CH, and Z represents nitrogen; A represents C(O), m is zero or whole number from 1 to 3; t is whole number from 1 to 3; and p and q are whole number from 1 to 2; or to their pharmaceutically acceptable salts and solvates. Claimed invention also relates to method of obtaining said derivatives and to their application for treating condition with tachyquininamia.

EFFECT: obtaining pyperidine derivatives, which can be used for treating tachyquininamia.

14 cl, 29 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine derivatives of formula I and their pharmaceutically acceptable salts, which are selective inhibitors of kinases KDR, FGFR and PDGFR and can be used for treatment of oncological diseases. Compound of formula I corresponds to structural formula , where R1 is selected from group, including H, COR4 and COOCHR5OCOR4; R2 and R3 are independently selected from group, including C1-6alkyl, C1-6alkyl, substituted with not more than 4 groups, which are independently selected from group, including -NR5R6,-R5, -OR5-phenyl,-phenyl, substituted with not more than 2 groups, which are independently selected from group, including OR5 and -C1-4alkyl and heteroaryl, representing aromatic heterocyclic ring system, which contains not more than two rings and includes from 1 to 3 nitrogen atoms, and heterocyclyl, representing saturated cyclic radical, which includes from 1 to 3 nitrogen atoms; R5 and R6 are independently selected from group H and C1-5alkyl. Invention also relates to pharmaceutical compositions, containing said compounds of formula I and intermediate products.

EFFECT: obtaining new pyrimidine derivatives, which can be used for treating oncological diseases.

17 cl, 2 tbl, 27 ex

FIELD: agriculture.

SUBSTANCE: description is given to fungicide based on triazolpyrimidine derivatives with general formula of I , R1 - is possibly substituted by haloid C1-8alkyl or C3-6cycloalkyl possibly substituted by C1-6alkyl; R2 stands for hydrogen or C1-8alkyl; or R1 and R2, together with nitrogen atom to which they are bound, form 5-7-membered N-containing heterocyclic ring, possibly substituted by C1-6alkyl; R3 - phenyl substituted by haloid, C1-6alkyl, C1-6alkoxy or simultaneously by haloid and C1-6alkoxy; R4 - haloid for preserving wood from basidiomycetes destroying it, and to the method of preservation wood and woody materials.

EFFECT: producing substance for effective preservation of wood and woody materials.

2 cl

FIELD: chemistry.

SUBSTANCE: invention describes new heterocyclic compounds of the general formula I where A is -(CH)-, -N- or -CH2-N-; B is -(CH2)-, -(CH2-CH2)-; D is -(CH2)- or -(C=O)-; W is -(C=O)- or is absent; X is -NH(C=O)- or is absent; Y is oxygen or sulfur; L is hydrogen, -C(O)NHR3 or -C(=O)OR4; R1 is C1-12alkyl; C6-10aryl; C1-6alkoxy; C6-10aralkyl; C6-10aralkyloxy; R2 is saturated or non saturated C1-10alkyl, possibly substituted; C1-10alkenyl; C6-10aralkyloxy; C1-10alkanedienyl; C6-10aryl, possibly substituted; C6-10aralkyl, possibly substituted; benzodioxolyl; piperonyl; chromenonyl; alkyl-C(=O)-; 5-6-membered heteroaryl with one or two nitrogen atoms, or oxygen atom, or sulfur atom, and possibly substituted; R3 is a radical of the formula or benzene; where Ra is C1-10alkyl, possibly substituted; C1-10alkenyl; C3-10cycloalkyl; amino; C6-10aralkyl; possibly substituted; Rd is hydrogen; C6-10aralkyl, possibly substituted; R4 is C6-10aralkyl; on the condition that if A is -(CH)- then B is -(CH2)-, D is -(CH2)-, X is -NH(C=O)- and L is -C(=O)NHR3; if A is N then B is -(CH2-CH2)- and X is absent; if A is -CH2-N- then B is -(CH2)-, D is -(CH2)-, W is -(C=O)-, X is absent and L is hydrogen; the invention also describes a pharmaceutical composition containing the claimed compounds.

EFFECT: obtaining compound with NF-kB transcription inhibition effect, applicable in medicine.

7 cl, 3 tbl, 10 ex, 4 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to the new compounds of formula I which can be used in photopolymer composition hardening with catalyst, possible during rays, and as photoinitiators for coating preparation. In formulas (I) and (II) $ , in which R1 denotes phenyl, naphthyl, phenanthryl, anthryl, pyrenil 5,6,7,8-tetrahydro-2-naphthyl,5,6,7,8-tetrahydro-1-naphthyl, thienyl, tiantrenyl, anthraquinonyl, xantenyl, thioxantyl, phenoxantyinyl, carbazol, phenantridinyl, akridinyl, fluorenyl or phenoxazinyl, besides radicals is unsubstituted or once or several times substituted by C1-C18alkyl, C2-C18alkenyl, C1-C18haloalkyl, NO2, NR10R11, CN, OR12, SR12, halogen atom or radical of formula II or radical R1 denotes radical of formula III . R2 and R3 independently denote a hydrogen atom; R10, R11 R12 independently denote a hydrogen atom or C1-C18alkyl; R4 and R6 form C2-C12alkylen bridge, which is not substituted or substituted by or several C1-C4alkyl radicals; R15 denotes H or radical of formula II.

EFFECT: production of the nitrogen bases that can be used as a photopolymer composition, hardening with catalyst, and as photoinitiator for coating.

11 cl, 4 tbl, 21 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new pyrazolopyrimidines with general formula (I) with fungicidal and bactericidal activity for fighting harmful organisms as well as medium theirs base. In the compounds with formulae (I) R1 represents an amino group, unsubstituted or substituted C1-6alkyl, in which substitutes are chosen from a group, containing amino, cyano, haloid, hydroxy, C1-6alkylthio, C1-6alkyloxy, C1-6alkoxycarbonyl, C3-6cycloalkyl, haloid- C1-6alkyl, haloid-C3-6cycloalkyl, C2-8dialkylamino, 5-member heterocyclyl, in which the heteroatoms are chosen from 1-2 atoms of oxygen or sulphur; C2-6alkenyl, C2-4alkynyl, C3-6cycloalkyl, possibly substituted with a halogen atom or haloidC1-6alkyl, C1-6alkylamino, di-C1-6 alkylamino, C2-6alkenylamino, C3-6cycloalkylamino, R2 represents hydrogen or C1-6alkyl, or R1 and R2 together with a nitrogen atom, to which they are bonded, form an unsubstituted or substituted by halogen, C1-4alkyl, 5-6-member heterocylcle, containing one nitrogen atom and 1-2 oxygen atoms, annelated phenyl ring or ethylene cross-link; C1-4alkoxycarbonylamino group, 5-6-member heterocyclic ring, containing 1-2 heteroatoms, chosen from nitrogen, oxygen and sulphur, R3 represents unsubstituted or substituted phenyl, in which the substitutes are chosen from halogen atoms, haloid-C1-6alkyl, X1 represents hydrogen or haloid and X2 represents haloid, cyano-, nitro, C1-6alkyl, C1-6alkyl halide, C3-6cycloalkyl, formyl, thiocarbamoil, alkoxycarbonyl or C1-6alkoxyaminoalkyl, as well as salts of formula (I) compounds, where R1 represents an amino group, with acids. The invention also relates to new intermediate compounds with general formulae (II) and (VI), where Y1 represents haloid, which can be used for obtaining formula (I) compounds.

EFFECT: obtaining pyrazolopyramidines with fungicidal and bactericidal activity for fighting harmful organisms.

4 cl, 3 dwg, 13 tbl, 475 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: description is given of new pyrrolo[2,1-f][1,2,4]triazine with general formula I , where Z represents O or N, under the condition that, when Z represents O, R41 is absent, and when Z represents N, R41 represents hydrogen; Y is absent; X represents O, NHCO2 or is absent; R1 and R6 represent hydrogen; R3 represents inferior alkyl; R42 represents a radical with formula , where R43 represents hydrogen or fluorine; R44 represents methyl or hydrogen; R2 represents hydrogen or inferior alkyl, possibly single or multi-substituted; if X is absent, R2 represents 1,3,4-oxadiazolyl, substituted with an alkyl halide, under the condition that, R2 cannot represent hydrogen, if X represents -NHCO2-, concrete representatives of the given series, pharmaceutical compositions, and methods of treating proliferative diseases and cancer.

EFFECT: obtaining new kinase inhibitors for treating proliferative diseases and cancer.

11 cl, 83 ex, 5 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

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