Novel vanilloid receptor ligands and use thereof in producing medicinal agents

FIELD: chemistry.

SUBSTANCE: invention relates organic chemistry and specifically to novel pyridine amide derivatives of general formula I where n equals 1; R1 and R2 together denote a residue selected from a group consisting of -CH=N-NH- and -CH=CH-N=CH-, which is bonded in any desirable direction to the parent structure or R2 and R3 together denote a residue selected from a group consisting of -CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is bonded in any desirable direction to the parent structure, or R3 and R4 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, or R4 and R5 together denote a -CH=N-NH- residue, which is bonded in any desirable direction to the parent structure, and the rest of the residues R1, R2, R3, R4 and R5, mutually independently, in each case denote H; where R28 denotes F; Cl; Br or I; R29 and R30, mutually independently, in each case denote -NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34; where R31, R32, R33 and R34, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R6 denotes H or denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; R7 denotes hydrogen or -OH; R denotes -CF3; or denotes an unsubstituted tert-butyl residue; T denotes C-R35 and U denotes C-R36, V denotes N and W denotes C-R38; where R35 and R36 denote H; where R38 denotes -NR40R41; -OR42 or -SR43; where R40, R41, R42 and R43, mutually independently, in each case denote a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; or denote a saturated, unsubstituted 3-, 4-, 5-, 6-, 7-, 8- or 9-member cycloaliphatic residue, or where R40 and R41 in each case together with a nitrogen atom as a ring member which binds them together, form a saturated 6-member heterocycloaliphatic residue, optionally substituted with one R57 residue, where R57 denotes a straight or branched, saturated, unsubstituted aliphatic C1-10 residue; in each case in form of corresponding physiologically acceptable salts. The invention also relates to a method of producing a compound of formula I, a medicinal agent based on the compound of formula I and use of the compound of formula I.

EFFECT: obtaining novel amide derivatives of pyridine, useful in treating vanilloid receptor 1 mediated diseases.

25 cl, 1 tbl, 18 ex

 

The text descriptions are given in facsimile form.

1. Substituted compounds of General formula I,

in which
n takes a value of 1;
R1and R2together denote a residue selected from the group consisting of-CH=N-NH - and-CH=CH-N=CH-, which is attached in any desired direction to the parent structure,
or R2and R3together denote a residue selected from the group consisting of-CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N - which is attached in any desired direction to the parent structure,
or R3and R4together denote a residue-CH=N-NH-, which is attached in any desired direction to the parent structure,
or R4and R5together denote a residue-CH=N-NH-, which is attached in any desired direction to the parent structure,
and other residues R1, R2, R3, R4and R5mutually independently, in each case denote H;
where R28means F; Cl; Br or I;
R29and R30mutually independently, in each case, the mean-NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34;
where R31,R32, R33and R34mutually independently, in each case denote a linear or branched, saturated, unsubstituted aliphatic C1-10the rest;
R6means H or means linear or branched, saturated, unsubstituted aliphatic C1-10the rest;
R7means hydrogen or-OH;
R8means-CF3; means or unsubstituted tert-botilony the rest;
T means C-R35and U represents C-R36V denotes N, and W denotes C-R38;
where R35and R36denote H;
where R38means-NR40R41; -OR42or-SR43;
where R40, R41, R42and R43mutually independently, in each case denote a linear or branched, saturated, nezamedin the th aliphatic C 1-10the remainder; or means a saturated, unsubstituted 3-, 4-, 5-, 6-, 7-, 8 - or 9-membered cycloaliphatic residue,
or
where R40and R41in each case, together with the nitrogen atom as a ring member, connecting them together, form a saturated 6-membered geterotsiklicheskikh residue, optionally substituted with 1 remainder R57;
where R57means a linear or branched, saturated, unsubstituted aliphatic C1-10the rest;
in each case in the form of corresponding physiologically acceptable salts.

2. Compounds according to claim 1, characterized in that
n takes a value of 1;
R1and R2together denote a residue selected from the group consisting of-CH=N-NH - and-CH=CH-N=CH-, which is attached in any desired direction to the parent structure,
or R2and R3together denote a residue selected from the group consisting of-CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is attached in any desired direction to the parent structure,
or R3and R4together denote a residue-CH=N-NH-, which is attached in any desired direction to the parent structure,
or R4and R5together denote a residue-CH=N-NH-, which is attached in any desirable is upravlenii the parent,
and other residues R1, R2, R3, R4and R5mutually independently, in each case denote H;
R6means H or denotes an alkyl residue selected from the group consisting of isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, methyl, ethyl and n-propyl;
R7means hydrogen or-OH;
R8means-CF3; or means tert-botilony the rest;
T means C-R35and U represents C-R36V denotes N, and W denotes C-R38;
R28means F; Cl; I;
R29and R30mutually independently, in each case, the mean-NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34;
R31, R32, R33and R34mutually independently, in each case denote an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl and n-pentile;
R35and R36denote H;
R38means-NR40R41; -OR42or-SR43;
R40, R41, R42and R43mutually independently, in each case denote a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentile, 3-pentile, n-heptyl, 4-heptyl, n-octyle, n-Manila, 5-Manila, (2,6)-dimethyl-hept-4-yl, 3-methylbutyl, n-hexyl, (3,3)di is ethylbutyl;
mean residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
or
R40and R41in each case, together with the nitrogen atom as a ring member, joining them together form a residue selected from the group consisting of piperidinyl, piperazinil, morpholinyl and thiomorpholine, heterocyclizations of which in each case may be unsubstituted or substituted by 1 residue R57;
R57means an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl, sec-butyl, and isobutyl;
in each case in the form of corresponding physiologically acceptable salts.

3. Compounds according to claim 1, characterized in that
n means 1;
R1and R2together denote a residue selected from the group consisting of-CH=N-NH - and-CH=CH-N=CH-, which is attached in any desired direction to the parent structure,
or R2and R3together denote a residue selected from the group consisting of-CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is attached in any desired direction to the parent structure,
or R3and R4together denote a residue-CH=N-NH-, which is attached in lubomilae direction to the parent structure,
or R4and R5together denote a residue-CH=N-NH-, which is attached in any desired direction to the parent structure,
and other residues R1, R2, R3, R4and R5mutually independently, in each case denote H;
R6means H or denotes an alkyl residue selected from the group consisting of isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, methyl, ethyl and n-propyl;
R7means hydrogen or-OH;
R8means-CF3; tert-butyl;
T means C-R35and U represents C-R36and V denotes N, and W denotes C-R38;
R28means F; Cl; Br or I;
R29and R30mutually independently, in each case, the mean-NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33; -S-R34;
R31, R32, R33and R34mutually independently, in each case denote an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, and n-pentile;
R35and R36denote H;
R38means-NR40R41; -OR42; -SR43;
R40, R41, R42and R43mutually independently, in each case denote a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentile-pentile, n-hexyl, (3,3)-dimethylbutyl;
mean residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl;
or
R40and R41in each case, together with the nitrogen atom as a ring member, joining them together form a residue selected from the group consisting of piperidinyl, piperazinil, morpholinyl and thiomorpholine, heterocyclizations of which in each case may be unsubstituted or substituted by 1 residue R57;
R57means an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl, sec-butyl, and isobutyl;
in each case in the form of corresponding physiologically acceptable salts.

4. Compounds according to claim 1, characterized in that
n means 1;
R1and R2together denote a residue selected from the group consisting of-CH=N-NH - and-CH=CH-N=CH-, which is attached in any desired direction to the parent structure,
or R2and R3together denote a residue selected from the group consisting of-CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is attached in any desired direction to the parent structure,
or R3and R4together denote a residue-CH=N-NH-,which is attached in any desired direction to the parent structure,
or R4and R5together denote a residue-CH=N-NH-, which is attached in any desired direction to the parent structure,
and other residues R1, R2, R3, R4and R5mutually independently, in each case denote H;
R6means H or denotes an alkyl residue selected from the group consisting of isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, methyl, ethyl and n-propyl;
R7means hydrogen or-OH;
R8means-CF3; tert-butyl;
T means C-R35and U represents C-R36and V denotes N, and W denotes C-R38;
R28means F; Cl; Br or I;
R29and R30mutually independently, in each case, the mean-NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33or-S-R34;
R31, R32, R33and R34mutually independently, in each case denote an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, and n-pentile;
R35and R36in each case denote H;
R38means-NR40R41; -OR42; -SR43;
R42and R43mutually independently, in each case denote a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentile, penttila, n-hexyl, and (3,3)-dimethylbutyl;
or denote a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;
R40and R41in each case, together with the nitrogen atom as a ring member, joining them together form a residue selected from the group consisting of piperidinyl, piperazinil and morpholinyl, heterocyclizations of which in each case may be unsubstituted or substituted by 1 residue R57;
R57means an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl, sec-butyl, and isobutyl;
in each case in the form of corresponding physiologically acceptable salts.

5. Compounds according to claim 1, characterized in that
n means 1;
R1and R2together denote a residue selected from the group consisting of-CH=N-NH - and-CH=CH-N=CH-, which is attached in any desired direction to the parent structure,
or R2and R3together denote a residue selected from the group consisting of-CH=N-NH-; -CR28=N-NH-; -S-C(=S)-NH-; -S-CR29=N-; -N=CR30-O-; -N=CH-NH-; -N=N-NH-; -O-CH2-O-; -CH2-CH2-CH2-NH, -O-CH2-CH2-O-; -N=CH-CH=N-; -CH=CH-CH=N-, which is attached in any desired direction to the parent structure,
or R3and R4together denote a residue-CH=N-NH-, to the which is attached in any desired direction to the parent structure,
or R4and R5together denote a residue-CH=N-NH-, which is attached in any desired direction to the parent structure,
and other residues R1, R2, R3, R4and R5mutually independently, in each case denote H;
R6means H or denotes an alkyl residue selected from the group consisting of isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, methyl, ethyl and n-propyl;
R7means hydrogen or-OH;
R8means-CF3; tert-butyl;
T means C-R35and U represents C-R36and V denotes N, and W denotes C-R38;
R28means F; Cl; Br or I;
R29means-NH-C(=O)-R31; -NH2; -NH-S(=O)2-R32; -NH-C(=O)-O-R33or-S-R34;
R30means-NH2;
R31, R32, R33and R34mutually independently, in each case denote an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, and n-pentile;
R35and R36in each case denote H;
R38means-NR40R41; -OR42; -SR43;
R42and R43mutually independently, in each case denote a residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentile, 3-pentile, n-hexyl is, and (3,3)-dimethylbutyl;
or denote a residue selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl;
R40and R41in each case, together with the nitrogen atom as a ring member, joining them together form a residue selected from the group consisting of piperidinyl, piperazinil and morpholinyl, heterocyclizations of which in each case may be unsubstituted or substituted by 1 residue R57;
R57means an alkyl residue selected from the group consisting of methyl, ethyl, n-propyl, isopropyl, tert-butyl, n-butyl, sec-butyl, and isobutyl;
in each case in the form of corresponding physiologically acceptable salts.

6. Compounds of General formula Ib according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8and R42matter according to claim 3;
in each case in the form of corresponding physiologically acceptable salts.

7. Compounds of General formula Ib according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8and R42matter according to claim 4;
in each case in the form of corresponding physiologically acceptable salts.

8. Compounds of General formula Ib according to claim 1,

in which
D is N; and
R1, R2, R3, R4, R5, R8and R42matter according to claim 5;
in each case in the form of corresponding physiologically acceptable salts.

9. Compounds of General formula Ic according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8and R43matter according to claim 3;
in each case in the form of corresponding physiologically acceptable salts.

10. Compounds of General formula Ic according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8and R43matter according to claim 4;
in each case in the form of corresponding physiologically acceptable salts.

11. Compounds of General formula Ic according to claim 1,

in which
D is N; and
R1, R2, R3, R4, R5, R8and R43matter according to claim 5;
in each case in the form of corresponding physiologically acceptable salts.

12. Compounds of General formula Id according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8, R40and R41matter according to claim 3;
in each case in the form of corresponding physiologically acceptable salts.

13. Soy is inane General formula Id according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8, R40and R41matter according to claim 4;
in each case in the form of corresponding physiologically acceptable salts.

14. Compounds of General formula Id according to claim 1,
,
in which
D is N; and
R1, R2, R3, R4, R5, R8, R40and R41matter according to claim 5;
in each case in the form of corresponding physiologically acceptable salts.

15. Compounds according to claim 1, selected from the group consisting of
[13] 2-(1H-benzo[d]imidazol-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[15] 2-(1H-benzo[d][1,2,3]triazole-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[22] 2-(1H-benzo[d][1,2,3]triazole-5-yl)-N-((2-butoxy-6-tert-butylpyridinium-3-yl)methyl)propanamide,
[23] 2-(1H-benzo[d]imidazol-5-yl)-N-((2-butoxy-6-tert-butylpyridinium-3-yl)methyl)propanamide,
[24] 2-(1H-benzo[d][1,2,3]triazole-5-yl)-N-((6-tert-butyl-2-(4-methylpiperidin-1-yl)pyridine-3-yl)methyl)propanamide,
[25] 2-(1H-benzo[d]imidazol-5-yl)-N-((6-tert-butyl-2-(4-methylpiperidin-1-yl)pyridine-3-yl)methyl)propanamide,
[26] 2-(1H-benzo[d][1,2,3]triazole-5-yl)-N-((6-tert-butyl-2-(cyclohexylthio)pyridine-3-yl)methyl)propanamide,
[27] 2-(1H-benzo[d]imidazol-5-yl)-N-((6-tert-butyl-2-(cyclohexylthio)PI is one-3-yl)methyl)propanamide,
[28] N-((2-butoxy-6-tert-butylpyridinium-3-yl)methyl)-2-(2-oxo-2,3-dihydrobenzo[d]thiazol-6-yl)propanamide,
[29] N-(2-butoxy-6-tert-butylpyridinium-3-ylmethyl)-2-(2-atlantarealestate-6-yl)-propionamide,
[30] N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(2-(methylthio)benzo[d]thiazol-6-yl)propanamide,
[31] N-((2-butoxy-6-tert-butylpyridinium-3-yl)methyl)-2-hydroxy-2-(2-(methylthio)benzo[d]thiazol-6-yl)propanamide,
[32] N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(2-thioxo-2,3-dihydrobenzo[d]thiazol-6-yl)propanamide,
[33] N-((6-tert-butyl-2-(4-methylpiperidin-1-yl)pyridine-3-yl)methyl)-2-(2-thioxo-2,3-dihydrobenzo[d]thiazol-6-yl)propanamide,
[34] N-((6-tert-butyl-2-(4-methylpiperidin-1-yl)pyridine-3-yl)methyl)-2-(2-(methylthio)benzo[d]thiazol-6-yl)propanamide,
[35] 2-(2-aminobenzo[d]oxazol-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[37] 2-(2-acetamidobenzoic[d]thiazol-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[38] 2-(2-aminobenzo[d]thiazol-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[39] N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(2-(methylsulfonyl)benzo[d]thiazol-6-yl)propanamide,
[40] tert-butyl-6-(1-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methylamino)-1-oxoprop-2-yl)benzo[d]thiazol-2-ylcarbamate,
[41] 2-(2-acetaminophen what about the[d]thiazol-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[42] 2-(2-acetamidobenzoic[d]thiazol-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[44] 2-(1H-indazol-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[45] 2-(3-fluoro-1H-indazol-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[46] N-((2-butoxy-6-tert-butylpyridinium-3-yl)methyl)-2-(1H-indazol-5-yl)propanamide,
[48] N-((6-tert-butyl-2-(cyclohexylthio)pyridine-3-yl)methyl)-2-(1H-indazol-5-yl)propanamide,
[49] N-(2-butoxy-6-tert-butylpyridinium-3-ylmethyl)-2-(2-thioxo-2,3-dihydrobenzofuran-6-yl)-propionamide,
[52] 2-(2-aminobenzo[d]thiazol-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[55] tert-butyl-6-(1-((6-tert-butyl-2-(4-methylpiperidin-1-yl)pyridine-3-yl)methylamino)-1-oxoprop-2-yl)benzo[d]thiazol-2-ylcarbamate,
[56] 2-(2-aminobenzo[d]thiazol-6-yl)-N-((6-tert-butyl-2-(4-methylpiperidin-1-yl)pyridine-3-yl)methyl)propanamide,
[58] 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)acetamide", she
[59] N-((2-(cyclohexylthio)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acetamide", she
[60] 2-(benzo[d][1,3]dioxol-5-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[62] 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[66] -((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(quinoline-6-yl)propanamide,
[67] N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-2-(cinoxacin-6-yl)propanamide,
[70] 2-(1H-indazol-4-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
[71] 2-(1H-indazol-6-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide and
[72] 2-(1H-indazol-7-yl)-N-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)propanamide,
in each case in the form of corresponding physiologically acceptable salts.

16. Compounds according to claim 1, characterized in that FLIPR analysis using cells CHO-K1, which were transliterowany human genome VR1, at a concentration of less than 2000 nm, preferably less than 1000 nm, particularly preferably less than 300 nm, more preferably less than 100 nm, still more preferably less than 75 nm, more preferably less than 50 nm and most preferably less than 10 nm, they lead to an approximately 50%increase substitution of capsaicin present in a concentration of 100 nm.

17. The method of obtaining compounds of one or more of claims 1 to 16, characterized in that at least one compound of General formula II,
,
in which R8, U, T, V, and W have the values in accordance with one or more of claims 1 to 16, m is 0, 1, 2 or 3 and R is hydrogen or means linear or branched C 1-6the alkyl residue is converted into the reaction medium, in the presence of at least one reducing agent, preferably in the presence of at least one reducing agent selected from the group consisting of sodium hydride, potassium hydride, lithium aluminum hydride, sodium borohydride and hydride di(isobutyl)aluminum
obtaining at least one of the compounds of General formula III,
,
in which R8, U, T, V and W have the values in accordance with one or more of claims 1 to 16, and m is 0, 1, 2 or 3, and the specified connection does not necessarily cleaned and/or emit,
and at least one compound of General formula III is converted into the reaction medium in the presence of diphenylphosphinite or in the presence of HN3obtaining at least one of the compounds of General formula IV,
,
in which R8, U, T, V and W have the values in accordance with one or more of claims 1 to 16, and m is 0, 1, 2 or 3, and the specified connection does not necessarily cleaned and/or emit,
and at least one compound of General formula IV is converted into the reaction medium in the presence of at least one reducing agent, preferably in the presence of at least one reducing agent selected from the group consisting of sodium hydride, potassium hydride, aluminum is of lithium hydride, of sodium borohydride and hydride di(isobutyl)aluminum
or in the reaction medium in the presence of a catalyst, preferably in the presence of a catalyst based on platinum or palladium, particularly preferably in the presence of palladium on charcoal, and in the presence of hydrogen or in the presence of hydrazine
or in the reaction medium in the presence of triphenylphosphine
obtaining at least one of the compounds of General formula V,
,
in which R8, U, T, V and W have the values in accordance with one or more of claims 1 to 16, and m is 0, 1, 2 or 3, and the specified connection does not necessarily cleaned and/or emit,
or at least one compound of General formula VI,
,
in which R8, U, T, V and W have the values in accordance with one or more of claims 1 to 16, and m is 0, 1, 2 or 3, turn in the reaction medium
in the presence of at least one catalyst, preferably in the presence of at least one catalyst based on palladium or platinum, particularly preferably in the presence of palladium on charcoal, in an atmosphere of hydrogen, optionally in the presence of at least one acid, preferably in the presence of hydrochloric acid,
or in the presence of at least one reducing agent selected from the group consisting of the C BH 3S(CH3)2, lithium aluminum hydride and sodium borohydride, optionally in the presence of NiCl2,
obtaining at least one of the compounds of General formula V, optionally in the form of a corresponding salt, preferably in the form of the corresponding hydrochloride, and the specified connection does not necessarily cleaned and/or emit,
and at least one compound of General formula V is introduced into reaction with at least one compound of General formula VII,
,
in which R1, R2, R3, R4, R5, R6and R7have values in accordance with one or more of claims 1 to 16, in a reaction medium, optionally in the presence of at least one suitable agent combination, optionally in the presence of at least one base,
or at least one compound of General formula VIII,
,
in which R1, R2, R3, R4, R5, R6and R7have values in accordance with one or more of claims 1 to 16, and LG denotes a leaving group, preferably chlorine atom or bromine, in a reaction medium, optionally in the presence of at least one base, obtaining at least one of the compounds of General formula I,
,
in which T, U, V, W, R1, R2, R , R4, R5, R6R7and R8have values in accordance with one or more of claims 1 to 16, and n denotes 1, 2, 3 or 4, and the specified connection does not necessarily purified and/or isolated.

18. The method of obtaining at least one compound according to one or more of claims 1 to 16, characterized in that at least one compound of General formula X,
,
in which R8, U, T, V and W have the values in accordance with one or more of claims 1 to 16, enter into a reaction with at least one compound of General formula VII,
,
in which R1, R2, R3, R4, R5, R6and R7have values in accordance with one or more of claims 1 to 16, in a reaction medium, optionally in the presence of at least one suitable agent combination, optionally in the presence of at least one base, obtaining at least one of the compounds of General formula Im,
,
in which T, U, V, W, R1, R2, R3, R4, R5, R6, R7and R8have values in accordance with one or more of claims 1 to 16, and this compound is optionally purified and/or isolated.

19. Medicine to use for the treatment of disorders or diseases which are at least an hour is ichno mediated by vanilloideae receptors 1 (VR1/TRPV1 receptors), containing at least one compound according to one or more of claims 1 to 16, and optionally one or more physiologically acceptable auxiliary substances.

20. Drug in claim 19 for the treatment or prevention of one or more diseases selected from the group consisting of pain, preferably of pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and visceral pain; joint pain; hyperalgesia; allodynia; causalgia and migraines.

21. Drug in claim 19 for the treatment or prevention of one or more diseases selected from the group consisting of depression; neuropathy; nerve damage; neurodegenerative diseases, preferably selected from the group consisting of multiple sclerosis, Alzheimer's disease, Parkinson's disease and horei Huntington; cognitive dysfunctions, preferably cognitive States insufficiency, particularly preferably memory disorders; epilepsy.

22. Drug in claim 19 for the treatment or prevention of one or more diseases selected from the group consisting of respiratory diseases, preferably selected from the group consisting of asthma, bronchitis and pneumonia; coughing; urinary incontinence; hyperactivity bladder (GUMP); C the illnesses and/or injuries of the gastrointestinal tract; ulcers duodenal ulcers; gastric ulcers; irritable bowel syndrome; stroke; eye irritation; skin irritation; neurotic skin conditions; allergic skin diseases; psoriasis; vitiligo; herpes simplex; inflammations, preferably inflammations of the intestine, the eyes, the bladder, the skin or the mucous membrane of the nose; diarrhea; pruritus; osteoporosis; arthritis; osteoarthritis; rheumatic diseases; eating disorders, preferably selected from the group consisting of bulimia, cachexia, anorexia and obesity; dependency on medicines; misuse of drugs; withdrawal symptoms associated with dependency on medicines; development of resistance to medicines, preferably to natural or synthetic opioids; drug dependence; drug abuse; withdrawal symptoms associated with drug dependency; alcohol dependence; alcohol abuse and withdrawal symptoms associated with dependency on alcohol; to stimulate diuresis; to reduce excessive excretion of sodium in the urine; for influencing the cardiovascular system; for increasing focus; for treatment of wounds and burns; for treatment of ruptures of the nerves; for increasing libido; for modulating locomotor activity; and is of cialisis; for local anesthesia; and/or suppression of undesirable side effects, preferably selected from the group consisting of hyperthermia, high blood pressure and spasm of the bronchial tubes caused by the introduction agonists vanilloideae receptor 1 (VR1/TRPV1 receptor), preferably selected from the group consisting of capsaicin, resiniferatoxin, olvanil, arvanil, assuming your-249665, assuming your-249482, novania and capivara.

23. The use of at least one compound according to one or more of claims 1 to 16 for the manufacture of a medicine for treating or preventing one or more diseases selected from the group consisting of pain, preferably of pain selected from the group consisting of acute pain, chronic pain, neuropathic pain and visceral pain; joint pain; hyperalgesia; allodynia; causalgia and migraines.

24. The use of at least one compound according to one or more of claims 1 to 16 for the manufacture of a medicine for treating or preventing one or more diseases selected from the group consisting of depression; neuropathy; nerve damage; neurodegenerative diseases, preferably selected from the group consisting of multiple sclerosis, Alzheimer's disease, Parkinson's disease and horei Huntington; cognitive dysfunction, preferably SOS is ojani cognitive failure, particularly preferably memory disorders; epilepsy.

25. The use of at least one compound according to one or more of claims 1 to 16 for the manufacture of a medicine for treating or preventing one or more diseases selected from the group consisting of respiratory diseases, preferably selected from the group consisting of asthma, bronchitis and pneumonia; coughing; urinary incontinence; hyperactivity bladder (GUMP); diseases and/or injuries of the gastrointestinal tract; duodenal ulcers; gastric ulcers; irritable bowel syndrome; stroke; eye irritation; skin irritation; neurotic skin conditions; allergic skin diseases; psoriasis; vitiligo; herpes simplex; inflammations, preferably inflammations of the intestine, the eyes, the bladder, the skin or the mucous membrane of the nose; diarrhea; pruritus; osteoporosis; arthritis; osteoarthritis; rheumatic diseases; eating disorders, preferably selected from the group consisting of bulimia, cachexia, anorexia and obesity; dependency on medicines; misuse of drugs; withdrawal symptoms associated with dependency on medicines; development of resistance to medicines, preferably to natural or synthetic opioids; is depending on the drug; drug abuse; withdrawal symptoms associated with drug dependency; alcohol dependence; alcohol abuse and withdrawal symptoms associated with dependency on alcohol; to stimulate diuresis; to reduce excessive excretion of sodium in the urine; for influencing the cardiovascular system; for increasing focus; for treatment of wounds and burns; for treatment of ruptures of the nerves; for increasing libido; for modulating locomotor activity; for anxiolysis; for local anaesthesia; and/or suppression of undesirable side effects, preferably selected from the group consisting of hyperthermia, high blood pressure and spasm of the bronchial tubes caused by the introduction agonists vanilloideae receptor 1 (VR1/TRPV1 receptor), preferably selected from the group consisting of capsaicin, resiniferatoxin, olvanil, arvanil, assuming your-249665, assuming your-249482, novania and capivara.



 

Same patents:

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: chemistry.

SUBSTANCE: invention refers to organic chemistry, more specifically to a method for preparing N-(1,5,3-dithiazocynan-3-yl)amides of formula , wherein R=p-C5H4N (a), (CH3)3CO (b), o-CH3OC6H4 (c), which can find application as biologically active compounds, selective sorbents and precious metal extractants. Substance of the method consists in the reaction of N1,N1,N7,N7 - tetramethyl-2,5-dithiaheptane-1,7-diamine with hydrazides RC(O)NHNH2 in the presence of the catalyst samaric nitrate crystallohydrate Sm(NO3)3·6H2O at temperature 65-75°C for 20-26 h.

EFFECT: what is developed is a method for preparing new high-selectivity N-(1,5,3-dithiazocynan-3-yl)amides.

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention describes a compound of formula I , in which X1, X2, X3, X4 and X5 independently denote -CH- or N; or X3, X4 and X5 independently denote -CH- or N, and X1 and X2 independently denote C and are part of an additional 6-member aromatic ring; in which R1 denotes methyl or ethyl, or R1 denotes hydrogen; R2 denotes methyl, ethyl, propyl, tert-butoxy carbonylmethyl, allyl, difluoromethyl, ethylbenzene, methylbenzene, butenyl, hydroxyethyl, tolyl, pentenyl, methoxyethyl, butynyl, propynyl, methylcarbonyloxy, cyclopentyl, each of which can be substituted with one or more identical or different substitutes selected from R5; or R2 denotes hydrogen; R3 denotes alkyl, cycloalkyl, alkenyl, cycloalkenyl, alkynyl, halogenalkyl, hydroxyalkyl, heterocycloalkenyl, alkylaryl, arylalkyl, alkylalkoxycarbonyl, alkylcarbonyloxy or alkoxyalkyl, each of which can be substituted with one or more identical or different substitutes selected from R6; or R3 denotes hydrogen, -CH2-C(O)-heterocycloalkyl or -CH2-C(O)NR9-R12; R11 denotes one or more identical or different substitutes selected from hydrogen, halogen, cyano, amino, alkyl, methylthionyl, methylsulphonyl, amino, cyano or alkoxy; where R5, R6, R9, R12 are as indicated in claim 1, under the condition that R1, R2 and R3 cannot be methyl at the same time; under the condition that when R2 and R3 both denote hydrogen, R1 cannot be methyl or hydrogen; under the condition that when R1 denotes methyl or hydrogen, R2 denotes methyl and R3 denotes hydrogen when ring B cannot be phenyl; and pharmaceutically acceptable salts and N oxides thereof. The invention also describes a pharmaceutical composition for use in case of skin diseases, said composition containing a compound of formula I, and use of said compound in preparing a medicinal agent for preventing conditions associated with skin wounds.

EFFECT: novel compounds which can be useful in treating skin diseases are obtained and described.

19 cl, 304 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula 1:

or pharmaceutically acceptable salts thereof, where values of Cy1; Cy2; L1; L2, R; R1; Rx and Ry and R2 are given in claim 1.

EFFECT: compounds are suitable for use as Raf protein kinase inhibitors.

36 cl, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds, which represent (4,5-dihydrooxazol-2-yl)-(5,6,7,8-tetrahydroquinoxylan-5-yl)-amino and (4,5-dihydrooxazol-2-yl(-(5,6,7,8-tetrahydroquinolin-5-yl)-amino or their pharmaceutically acceptable salt. Said compounds are applied in methods of intraocular pressure reduction and treatment of pain in mammals who require it.

EFFECT: obtaining compounds, which are alpha-adrenergic agonists.

3 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described macrocyclic phenylcarbamates of formula (I), wherein A represents -C(=O)OR1 or -C(=O)-NH-SO2-R2, wherein R1 represents hydrogen or C1-C6alkyl; R2 represetns C3-7cycloalkyl, phenyl, thiazolyl or pyridyl each of which is optionally substituted by one or more substituted specified in C1-6alkyl, C1-6alkoxy, trifluoromethyl and halogen; X represents N or CH; E represents NR5; R5 represents hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl or C3-7cycloalkyl; n is equal to 4 or 5; wherein a dash line -----, adjoining the fragment -(CH2)n-, represents a double bond; and wherein the dash line in a five-merous cycle including X, represents a single bond, and R7 represents hydrogen; R8 is such as specified in the patent claim, or N-oxide thereof, a pharmaceutically acceptable additive salt or a pharmaceutically acceptable solvate possessing antiviral activity, and used as HCV inhibitors; as well as pharmaceutical compositions containing the above compounds as an active ingredient.

EFFECT: preparing the pharmaceutically acceptable additive salt or pharmaceutically acceptable solvate possessing antiviral activity.

10 cl, 23 ex, 1 tbl

FIELD: biotechnologies.

SUBSTANCE: invention relates to derivatives of [1-(benzyl)piperydine-4-yl]-([1,3,4]thiadiazole- 2-yl)amine and [1-(benzyl)piperydine-4-yl]-(thiazole-2-yl)amine of the formula (I) or their pharmaceutically acceptable salts, or their pharmaceutically acceptable salts, where R means hydrogen; R1 means phenyl, substituted with 1, 2 or 3 substitutes, each of them is independently selected from a group containing halogen, cyano, C1-4alkyl, perfluoroC1-4alkyl and perfluoroC1-4alkoxy; R2 means hydrogen or C1-4alkyl; R3 means hydrogen, trifluoromethyl or cyano; X means N or CR4, where R4 is trifluoromethyl. Also the invention relates to a pharmaceutical composition containing compounds of the formula as an active ingredient. The following derivatives are presented: derivatives of [1-(benzyl)piperydine-4-yl]-([1,3,4]thiadiazole-2-yl)amine and [1-(benzyl)piperydine-4-yl]-(thiazole-2-yl)amine of the formula (I) representing quick-dissociating antagonists of dopamine 2 receptors and used as medicinal agents for treatment or prevention of central nervous system.

EFFECT: improved properties of compounds.

7 cl, 22 ex

FIELD: chemistry.

SUBSTANCE: invention relates to bicyclosubstituted pyrazolon azo derivatives of formula

or pharmaceutically acceptable salts thereof, intermediate compounds of formula ,

as well as methods for production thereof, a pharmaceutical composition containing a compound of formula (II), and use thereof as a therapeutic agent, which is a thrombopoietin (TPO) mimetic, as well as use thereof as agonists of the thrombopoietin receptor. Values of substitutes in formulae (I) and (IA) are given in the claim.

EFFECT: obtaining bicyclosubstituted pyrazolon azo derivatives.

12 cl, 58 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel cyclic 5-nitropyridin-2-yl-thioalkenyl-4-dithiocarbamate derivatives of general formula (I) or pharmaceutically acceptable acid- or base addition salts thereof. The compounds have antifungal activity even in case of deep, subcutaneous and surface mycoses in humans, caused by strains (including those resistant to existing drugs) of mycosis causative agents. In general formula , R denotes nitro, cyano, halide-substituted C1-C6 alkyl group, n=1, 2 or 3. The invention also relates to use of compounds of formula (I), a method of producing said compounds, a pharmaceutical composition and a method for treatment using said compounds.

EFFECT: improved method.

12 cl, 2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), stereoisomers, trans- and cis-isomers, racemates or pharmaceutically acceptable salts thereof, having modulating activity on histamine H3-receptors. In formula (I) m equals 0; one of R1 and R2 is selected from a group which includes hydrogen, C1-10alkoxycarbonyl, amido-, carboxy-, C3-8cycloalkyl, halogen, -NRARB, (NRARB)carbonyl, or a group of formula -L2-R6; the other of R1 and R2 is selected from a group which includes hydrogen, halogen; each of R3a and R3b is independently selected from a group which includes hydrogen; each of R4 and R5 is independently selected from a group which includes C1-10alkyl and C1-10hydroxyalkyl; or R4 and R5, taken together with a nitrogen atom to which each is bonded, form a heteroaromatic ring of the type (a) or (b), where Q1 is O or C; Q2 is -N(R20)-; R20 is selected from a group which includes hydrogen and C1-10alkoxycarbonyl; each of p1 and p2 is independently equal to 1, 2 or 3; each of q1, q2, q3, q4 and q5 are independently equal to 0, 1 or 2; and wherein each carbon atom in the ring is substituted with hydrogen or 0, 1 or 2 substitutes, independently selected from a group which includes hydrogen, hydroxy group, fluorine, C1-10alkyl, C1-10hydroxyalkyl and C1-10fluoroalkyl; R6 is a phenyl, heterocycle or heterocycloC1-4alkyl, wherein the heterocycle is a 4-6-member aromatic or non-aromatic ring which contains 1 or 2 heteroatoms independently selected from N, O and S, optionally condensed with a benzene ring, wherein the phenyl or heterocycle can be unsubstituted or optionally substituted with one or more substitutes independently selected from a group which includes C1-4alkoxy, C1-4alkyl, cyano, halogen and oxo-; L is a bond or C1-4alkylene; L2 is a bond, C1-4alkylene, -C(=O)-, -SO2N(R14a)-, -N(R14a)SO2-, -C(O)N(R14a)-, -N(Rl4a)C(O)- or -N(R15)-; R10 is selected from a group which includes hydrogen; R14a is selected from a group which includes hydrogen; R15 is selected from a group which includes hydrogen; and RA and RB are independently selected from a group which includes hydrogen, C1-10alkyl, C1-10acyl, C1-4halogenalkyl, C1-10alkoxycarbonyl, C3-8cycloalkyl and C3-8cycloalkylcarbonyl. The invention also relates to a pharmaceutical composition which contains compounds of formula (I), a method for selective modulation of effects of histamine H3-receptors, use of said compounds in producing a medicament for treating a condition or disorder modulated by histamine H3-receptors, as well as specific compounds of formula (I).

EFFECT: improved properties of compounds.

18 cl, 2 tbl, 154 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (1) or salts thereof, where in formula (1) R1 is a lower C1-C6alkyl group, a lower C3-C6cycloalkyl group, a phenyl group, a heterocyclic group, which relates to a residue formed by removing a hydrogen atom from a saturated or unsaturated monocyclic heterocyclic ring containing one, two or three heteroatoms in the ring, selected from a nitrogen atom, an oxygen atom and a sulphur atom, or a phenyl(C1-C6alkyl) group; in cases when R1 is a lower C1-C6alkyl group, that lower C1-C6alkyl group can have, as substitute(s), one, two or three groups selected from a halogen atom, a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one or two heteroatoms in the ring, selected from a nitrogen atom and an oxygen atom, a carboxyl group, a lower C1-C6alkoxycarbonyl group, a lower C1-C6alkylamino group, a lower C1-C6alkylamino group, substituted with a lower C1-C6alkylamino group, a lower C1-C6alkylamino group, substituted with a phenyl group; in cases when R1 is a phenyl group, a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated or unsaturated monocyclic heterocyclic ring containing one, two or three heteroatoms in the ring, selected from a nitrogen atom, an oxygen atom or a sulphur atom, or a phenyl(C1-C6alkyl) group, that phenyl, heterocyclic or phenyl(C1-C6alkyl) group can contain, as substitute(s), one, two or three groups selected from a halogen atom, a lower C1-C6alkyl group, a hydroxyl group or a lower C1-C6alkoxy group; R2 is a hydrogen atom or a lower C1-C6alkyl group; R3 is a hydrogen atom or a lower C1-C6alkyl group; R4 and R5 can be identical or different and are a hydrogen atom or a lower C1-C6alkyl group; R6 is a hydrogen atom or a lower C1-C6alkyl group; R7 is a phenyl group or a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one heteroatom in the ring, selected from an oxygen atom and a sulphur atom; in cases where R7 is a phenyl group or a heterocyclic group which relates to a residue formed by removing a hydrogen atom from a saturated monocyclic heterocyclic ring containing one heteroatom in the ring, selected from an oxygen atom and a sulphur atom, that phenyl or heterocyclic group can contain, as substitute(s), one or two groups selected from a halogen atom, a lower C1-C6alkyl group, a hydroxyl group, a lower C1-C6alkoxy group and a nitro group; W is an oxygen atom or NR8; R8 is a hydrogen atom or a lower C1-C6alkyl group; X is an oxygen atom or a sulphur atom; Y is a lower C1-C6alkylene group; Z is an oxygen atom, a sulphur atom, NR9 or OCO; R9 is a hydrogen atom or a lower C1-C6alkyl group. The invention also relates to a pharmaceutical composition based on said compounds, having GR binding activity.

EFFECT: obtaining novel compounds and a pharmaceutical composition based on said compounds, which can be used in medicine as glucocorticoid receptor modulators.

10 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I and formula IV wherein the radical values are such as specified in cl. 1 and 4 of the patent claim, as well as to their therapeutically acceptable salts. Besides, the invention refers to a composition for treating cancer on the basis of the compounds of formula I, to using the compounds of formula I for preparing the therapeutic agent for treating cancer, as well as to using it for treating cancer.

EFFECT: there are prepared and described the new compounds which inhibit anti-apoptotic Bcl-2 and Bcl-x protein activity.

17 cl, 481 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: prevent invention refers to organic chemistry, namely to new quinolinone derivatives of general formula (I) or a pharmaceutically acceptable slat, hydrate or solvate thereof, wherein the above compound contains a flexible fragment specified in a group consisting of amide and an ester, directly conjugated with the substitute R1, and wherein A represents -O-(CH2)n-, wherein n represents an integer from 2 to 4; R1 represents phenyl substituted by one or two substitutes specified in a group consisting of halogen, OH and OCH3; R2, R3, R4 and R5 independently represents hydrogen, C1-4 alkyl or C1-4 alkoxy; R6 represents hydrogen or C1-4alkyl. Also, the invention refers to the compound of formula (II) and to a method of treating schizophrenia, acute mania, bipolar disorder or depression.

EFFECT: there are prepared new compounds showing the effective biological properties.

12 cl, 1 tbl, 68 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: invention refers to naphthalene carboxamide derivatives of general formula I which possess the properties of protein kinase or histone deacetylase inhibitors. The compounds can find application for preparing a drug for treating inflammatory diseases, autoimmune diseases, oncological disease, diseases of the nervous system and neurodegenerative diseases, allergies, asthma, cardiovascular diseases and metabolic diseases or disease related to hormonal diseases. In general formula I: , Z represents CH or N; each of the groups R1, R2 and R3 represents hydrogen, halogen, alkyl, alkoxy or trifluoromethyl; R4 represents or X represents a benzene ring or a pyridine ring; R5 represents one or more substitutes specified in a group consisting of hydrogen, halogen, alkyl, alkoxy or trifluoromethyl. The invention also refers to a method for preparing the above compounds, a pharmaceutical preparation and using them.

EFFECT: preparing the compounds which possess the properties of protein kinase or histone deacetylase inhibitors.

13 cl, 10 tbl, 6 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a piperazine compound presented by formula , wherein R1 represents C1-6 alkyl; R2 represents hydroxy, C1-6 alkyl which can contain a substitute specified in saturated or unsaturated 5-6 member heterocycle with 1-3 heteroatoms specified in oxygen and nitrogen, -(C=O)-N(R3)(R4) or -(C=O)-OR5; R3 and R4 may be identical or different, and each represents hydrogen or C1-6 alkyl which can contain a substitute specified in saturated or unsaturated 5-6 member heterocycle with 1-3 heteroatoms specified in oxygen and nitrogen, or R3 and R4 bound through a nitrogen atom whereto R3 and R4 are attached, can form a saturated heterocyclic group specified in 5-6 member heterocycle with 1-3 heteroatoms specified in oxygen and nitrogen; R5 represents hydrogen or C1-6 alkyl; and n represents 1 or 2; or a salt thereof. Also, the invention refers to a pharmaceutical compositions and an agent exhibiting prostaglandin-D-synthase activity and based on the compound of formula I, as well as to a method of preventing and treating a disease wherein prostaglandin D2 is involved.

EFFECT: there are prepared and described new compounds which may be effective in treating the diseases wherein prostaglandin D2 is involved.

11 cl, 19 ex, 4 tbl

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: invention refers to new uracil derivatives possessing human dUTPase inhibitory activity. In formula (I) n is equal to an integer 1 to 3; X member a bond, an oxygen atom, a sulphur atom, an alkenyl group containing 2 to 6 carbon atoms, a bivalent aromatic hydrocarbon group containing 6 to 14 carbon atoms, or a bivalent 5-7-merous saturated or unsaturated heterocyclic group containing 1 nitrogen or sulphur atom; Y means a bond or a linear or branched alkylene group containing 1 to 8 carbon atoms optionally having a cycloalkylydene structure containing 3 to 6 carbon atoms on one carbon atom; and Z means -SO2NR1R2 or -NR3SO2-R4, wherein R4 means an aromatic hydrocarbon group containing 6 to 14 carbon atoms which is optionally substituted by 1-2 substitutes, or an unsaturated 5-7-member heterocyclic group containing 1 nitrogen or sulphur atom which is optionally substituted by 1-2 halogen atoms; the radical values R1, R2 and the substitutes of the group R4 are presented in the patent claim.

EFFECT: invention relates to a pharmaceutical compositions comprising said compounds, to a human dUTPase inhibitor and a method of treating a human dUTPase-associated disease.

10 cl, 85 tbl, 179 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel carboxyl- or hydroxyl-substituted benzimidazole derivatives of formula (I), or pharmaceutically acceptable salts thereof, where R1 is selected from and , R2 is hydrogen; R3 is cyclohexyl or bicyclo[2.2.1]heptyl; R4 is phenyl, which is substituted in the 4th position with a halogen or a lower fluoroalkyl, or a pyridyl, which is substituted with 1 or 2 substitutes independently selected from halogen and a lower alkoxy group; R5 and R6 independently denote hydrogen or fluorine; R7 and R9 are independently selected from a group consisting of hydrogen, lower alkyl, halogen, lower alkoxy group, lower fluoroalkyl, lower fluoroalkoxy group and cyano group; R8 is -(CR12R13)n-COOH, where n equals 0, 1 or 2, and R12 and R13 are independently hydrogen or lower alkyl, or -O-(CR14R15)p-COOH, where p equals 1 or 2, and R14 and R15 are independently hydrogen or lower alkyl, or R14 and R15 together with the carbon atom with which they are bonded form a cycloalkyl ring, or R8 is tetrazole; R10 is a hydroxy group or -(CH2)p-COOH, where p equals 0 or 1; m equals 0 or 1; R11 is -COOH. The invention also relates to specific carboxyl- or hydroxyl-substituted benzimidazole derivatives and a pharmaceutical composition based on a compound of formula (I).

EFFECT: novel carboxyl- or hydroxyl-substituted benzimidazole derivatives, having selective activity with respect to farnesoid X receptor, are obtained.

26 cl, 126 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel of 2,4-pyrimidine diamine compounds of formula I, which inhibit degranulation of immune cells and can be used in treating cell reactions mediated by FcεRI or FcγRl receptors. In formula (I) each R2 and R4 is independently phenyl substituted with one or more R8 groups or a heteroaryl selected from a group consisting of , where the heteroaryl is optionally substituted with one or more R8 groups and at least one of R2 and R4 is a heteroaryl; R5 is selected from a group consisting of (C1-C6)alkyl, optionally substituted with one or more identical or different R8 groups, -ORd, -SRd, fluorine, (C1-C3)halogenalkyloxy, (C1-C3)perhalogenalkyloxy, -NRcRc, (C1-C3)halogenalkyl, -CN, -NO2, -C(O)Rd, -C(O)ORd, -C(O)NRcRc, -C(NH)NRcRc, -OC(O)Rd, -OC(O)ORd, -OC(O)NRcRc; -OC(NH)NRcRc, - [NHC(O)]nORd, R35 is hydrogen or R8; each Y is independently selected from a group consisting of O, S and NH; each Y1 is independently selected from a group consisting of O, S and NH; each Y2 is independently selected from a group consisting of CH, CH2, S, N, NH and NR37. Other values of radicals are given in the claim.

EFFECT: improved efficiency.

19 cl, 6 tbl.

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula III and their pharmaceutically acceptable salts, A represents (C1-C6)alkyl-O-, phenyl-(C1-C6)alkyl-O-; aryl, selected from phenyl, naphthyl, and which is possibly substituted by 1-3 substituents, given in the invention formula; or heteroaryl, which has four or five carbon atoms and one heteroatom, selected from oxygen, nitrogen and sulphur, which is possibly substituted by 1-3 substituents, given in the invention formula; B represents phenyl, possibly substituted by 1-3 substituents, where substituents are selected from (C1-C6)alkyl, (C3-C7)cycloalkyl, (C1-C6)alkyl-O-, hydroxy, amino and halogeno; and R1 and R2 independently represent (C1-C6)alkyl, phenyl-(C1-C6)alkyl-, hydroxy-(C1-C6)alkyl, (C3-C7)cycloalkyl, (C2-C6)alkenyl or (C2-C6)alkynyl; on condition that R1 is different from R2; where absolute configuration of asymmetric R1 and R2 -carrying carbon atom is mainly R-configuration. Invention also relates to pharmaceutical composition, possessing ability to modulate gene expression, methods of modulation of gene expression in host cell, method of regulating expression of endogenous or heterologous gene in transgenic subject, method of regulating transgenic expression in transgenic subject, method of polypeptide production and to method of obtaining formula IV compound. Method includes stages: a) interaction of formula V compound with formula IV compound with obtaining formula VII compound; b) reduction of formula VII compound with obtaining formula VIII compound, b) interaction of formula VIII compound with formula B-CO-LG compound, where B has values, given above, and LG is leaving group representing -F, -Cl or -Br, with formation of formula IX compound, d) removal of group R7CO2- from formula IX compound with obtaining formula X compound, e) interaction of formula X compound with formula A-CO-LG compound, where A has values, given above, and LG is leaving group, representing -F, -Cl or -Br, with obtaining formula IV compound ( compounds of formulas V, VI, VII, VIII, IX, X are given in the invention formula).

EFFECT: obtaining formula III compounds, possessing ability to modulate gene expression.

19 cl, 4 ex, 2 tbl, 78 ex

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