New coumarins, carboxamide derivatives thereof, methods of production, compositions and use

FIELD: chemistry.

SUBSTANCE: invention relates to new coumarin derivatives and their carboxamides, with general formula (I) , where R3 is chosen from a group consisting of H, carboxyl, alkyloxycarbonyl, 5'-(phenyloxadiazol-2')-yl, 5'-(pyridyl-4"-oxadiazol-2')-yl, , CONHR9, where R9 is chosen from a group consisting of fatty acids C2-C8, benzoxamido, isonicotinamido, unsubstituted, or mono-, or polysubstituted phenyl, in which the substitute can be hydroxy, C1-C8-alkoxy, CF3, carboxyl, alkyloxycarbonyl, OCH2CO2H, NO2, halogen, SO3H, SO2NHR11, where R11 is chosen from a group consisting of hydrogen, amidino, 2"-thizolyl, 3"-(511-methylisooxazolyl), 2"-pyrimidinyl, 2"-(4",6"-dimethylpyrimidinyl), 4"-(5",6"-dimethoxypyrimidinyl); R4 is chosen from a group consisting of hydrogen, CONHR10, where R10 is chosen from a group consisting of C2-C8 fatty acids, unsubstituted phenyl; R5 is chosen from a group consisting of H, C1-C4 alkyl; R6 is chosen from a group consisting of H, C1-C12-alkyl, halogen, NO2, CONHR13, where R13 is substituted phenyl; R7 is chosen from a group consisting of H, hydroxyl, C1-C4alkyl or alkoxyl, carboxyalkyleneoxyl, OCH2CONHR14, where R14 is chosen from a group consisting of unsubstituted, mono-, or polysubstituted phenyl, in which the substitute can be hydroxyl, OCH3, CF3, CO2H, CO2C2H5, NO2; R8 is chosen from a group consisting of H, C1-C4-alkyl or alkoxyl, NO2; under the condition that, when R3, R5 and R6 are H, and R7 is OH, R4 and R7 are not groups, chosen from H, C1-C6-alkyl or C1-C6-alkoxy. The invention also relates to pharmaceutical compositions based on formula I compounds and their use as medicinal preparations for protecting kidneys, for curing hypertonia, cardio-cerebrovascular diseases, non-achrestic diabetes, tumours, precancerous diseases and oedema.

EFFECT: enhanced effectiveness of the composition and treatment method.

17 cl, 6 tbl, 51 ex

 

The text descriptions are given in facsimile form.

1. The connection represented by the following General formula (I)

where R3selected from the group consisting of N, carboxyl, allyloxycarbonyl, 5'-(phenyloxazol-2')-yl, 5'-(pyridyl-4 ' -oxadiazol-2')-Il,
CONHR9where R9selected from the group consisting of fatty acids2-C8benzoctamine, isonicotinamide, unsubstituted or mono-, or preparation of polysubstituted phenyl, in which the Deputy may be a hydroxyl,1-C8-alkoxy, CF3carboxyl, allyloxycarbonyl, co2CO2N, NO2, halogen, SO3H, SO2Other11where R11selected from the group consisting of hydrogen, amidino, 2"-thiazolyl, 3"-(5"-methylisoxazole), 2"-pyrimidinyl, 2"-(4",6"-dimethylpyrimidine), 4"-(5",6"-dimethoxypyrimidine);
R4selected from the group consisting of hydrogen, CONHR10where R10selected from the group consisting of C2-C8fatty acids, unsubstituted phenyl;
R5selected from the group consisting of H, C1-C4of alkyl;
R6selected from the group consisting of H, C1-the 12-alkyl, halogen, NO2, CONHR13where R13represents a substituted phenyl;
R7selected from the group consisting of H, hydroxyl, C1-C4the alkyl or alkoxyl, carboxymethyloxime, OCH2CONHR14where R14selected from the group consisting of unsubstituted, mono - or preparation of polysubstituted phenyl, in which the Deputy may be a hydroxyl, co3, CF3, CO2H, CO2C2H5, NO2;
R8selected from the group consisting of H, C1-C4-alkyl or alkoxyl, NO2;
provided that when R3, R5and R6represent H, a R7IT means, R4and R7are groups selected from H, C1-C6-alkyl or C1-C6-alkoxy.

2. The compound according to claim 1, where R3selected from the group consisting of H, COOH, CO2With2H5, 5'-(phenyloxazol-2')-yl, 5'-(pyridyl-4 ' -oxadiazol-2')-Il,
CONHR9where R9is a n-butyric acid, o-, m-, p - phenol, o-, m-, p-carboxyphenyl, o-, m-, p-allyloxycarbonyl, methoxyphenyl, 3'-hydroxy-4'-carboxyphenyl, 3'-salicylic, 3'-salicylal, m-CF3-phenyl, 3'-CF3-4'-NO2-phenyl, 2'-CO2N-4'-itfeel, isonicotinamide, benzoctamine, 3'-carboxymethyloxime, 4'-am is desulfonylation, 4'-guanidinonaltrindole, 4'-(2"-thiazoleethanol)phenyl, 4'-(5"-methylisoxazole-3"-aminosulfonyl)phenyl, 4'-(pyrimidinyl-2-aminosulfonyl)phenyl, 4'-(4",6"-dimethylpyrimidine-2"-aminosulfonyl)phenyl, 4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenyl;
R4selected from the group consisting of N, CONHR10where R10as stated above;
R5selected from the group consisting of N, CH3;
R6selected from the group consisting of H, C2H5the h6H13, NO2, NH2, Cl, Br, CONHR13in which R13selected from the group consisting of 4-benzoic acid ethyl ester 4-benzoic acid;
R7selected from the group consisting of H, HE, CH3The co3, OCH2CONH14where R14selected from the group consisting of phenyl, o-, m - and p-hydroxyphenyl, o-, m - and p-carboxyphenyl, m - and p-ethoxycarbonylphenyl, m-CF3-phenyl, m-CF3-p-NR2-phenyl, p-CH3O-phenyl, 4-salicylal, 3-salicylal;
R8selected from the group consisting of N, CH3The co3, NO2;
provided that when R3, R5and R6represent H, a R7IT means, R4and R7are groups selected from H, C1-C6-alkyl or C1-C6-alkoxy.

3. The compound according to claim 1, having the following about the second formula (Ia):

in which R4, R5, R6, R7, R8defined in claim 1,
R is (CH2)3CO2N
,,;

4. The compound according to claim 1, which has the following General formula (Ib):

in which R4, R5, R6, R7, R8defined in claim 1,
R'2selected from the group consisting of H, HE, CO2N;
R'3selected from the group consisting of H, HE, CO2N, CF3The co2CO2N;
R'4selected from the group consisting of H, HE, CO2N, CO2C2H5, iodine, NO2, OCH3, SO3H, SO2NH2, SO2NH(C=NH)NH2,
,,
,,
each R'5and R'6represents N.

5. The compound according to claim 2, where R3, R4, R5, R6, R7, R8accordingly, choose from one of the combinations in the following group consisting of:
R3means p-CO2N-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means m-CO2N-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co ;
R3means o-CO2N-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means on-HE-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means m-HE-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means p-HE-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R5=R6=R8=H, R7=Co3;
R3means o-CO2N-p-iodinization, R4=R5=R6=R8=H, R7=OCH3;
R3=4'-ethoxycarbonylpyrimidine, R4=R5=R6=R8=H, R7=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3=4'-aminosulphonylphenyl, R4=R5=R6=R8=H, R7=OCH3;
R3=4'-guanidinonaltrindole, R4=R5=R6=R8=H, R7=OCH3 ;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=R5=R6=R8=H; R7=OCH3;
R3=4'-(2"-(4",6"-dimethylbenzenesulfonyl))phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3=4'-(5"-methylisoxazol-3"-aminosulfonyl)phenylenecarbonyl; R4=R5=R6=R8=H, R7=OCH3;
R3means p-och3-phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3means p-SO3N-phenylenecarbonyl, R4=R5=R6=R8=H, R7=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means m-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means o-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means p-HE-phenylenecarbonyl, R 4
=R5=R8=H, R6=C2H5, R7=OCH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=Co3;
R3=4'-ethoxycarbonylpyrimidine, R4=R5=R8=H, R6=R7=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R8=H, R6=R7=OCH3;
R3means m-CF3-4-NR2-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=4'-aminosulphonylphenyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=4'-guanidinonaltrindole, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=R5=R8=H
R6=C2H5, R7=OCH3;
R3=4'-(4",6"-dimethylpyrimidine-2'-aminosulfonyl)phenylenecarbonyl; R4=R 5
=R8=H, R6=C2H5, R7=OCH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl; R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=4'-(5"-methylisoxazol-3"-aminosulfonyl)phenylenecarbonyl; R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means p-och3-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means p-SO3N-phenylenecarbonyl, R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means m-CO2N-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means o-CO2N-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3; R8=CH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means o-CO2N-p-iodinization, R4=R5=R6 =H, R7=OCH3, R8=CH3;
R3=p-ethoxycarbonylpyrimidine, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-aminosulphonylphenyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-guanidinonaltrindole, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-(4",6"-dimethylpyrimidine-2"-aminosulfonyl)phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=4'-(5"-methylisoxazol-3"-aminosulfonyl)phenylenecarbonyl; R4=R5=R6=H, R7=OCH38
=CH3;
R3means p-och3-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means p-SO3N-phenylenecarbonyl, R4=R5=R6=H, R7=OCH3, R8=CH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=R6=H, R7=R8=OCH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R6=H, R7=R8=OCH3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R5=R6=H, R7=R8=OCH3;
R3means p-ethoxycarbonylpyrimidine, R4=R5=R6=H, R7=R8=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R6=H, R7=R8=OCH3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R5=R6=H, R7=R8=OCH3;
R3mean m BUT2CLO2O-phenylenecarbonyl, R4=R5=R6=N, R7=R8=Co3;
R3=4'-aminosulphonylphenyl, R4=R5=R6=N, R7=R8=OCH3;
R3=4'-guanidinonaltrindole, R4=R5=R6=N, R7=R8=OCH3;
R3means p-CO2 N-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means m-CO2N-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means o-CO2N-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means on-HE-phenylenecarbonyl, R4=R6=R8=H, R5=Snz, R7=Co3;
R3means m-HE-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means p-HE-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=p-ethoxycarbonylpyrimidine, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means m-CF3-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R6=R8=H, R7=OCH3, R5=CH3;
R3means 4 which is-aminosulphonylphenyl, R4=R6=R8=H, R5=CH3,
R7=OCH3;
R3=4'-guanidinonaltrindole, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R6=R8=H
R5=CH3, R7=OCH3;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=4'-(4",6"-dimethylpyrimidine-2"-aminosulfonyl)phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=Co3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=4'-(5"-methylisoxazol-3"-aminosulfonyl)phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3means p-och3-phenylenecarbonyl, R4=R6=R8=H, R5=CH3, R7=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R5 =R8=H, R6=Cl, R7=OCH3;
R3means p-ethoxycarbonylmethylene, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3=4'-aminosulphonylphenyl, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3=4'-guanidinonaltrindole, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R5=R8=H, R6=Cl, R7=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means o-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means o-CO2N-p-iodinization, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means p-ethoxycarbonylpyrimidine, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R8=H, R6=Br, R7=OCH3; R3=4'-aminosulphonylphenyl, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means p-och3-phenylenecarbonyl, R4=R5=R8=H, R6=Br, R7=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3means o-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=n-hexyl, R7=Co3;
R3=m-HE-p-CO2N-phenylenecarbonyl, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3=o-CO2N-p-iodinization, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3=p-ethoxycarbonylpyrimidine, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3means 4'-aminosulphonylphenyl, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3means p-och3-phenylenecarbonyl, R4=R5=R8=H, R6=n-hexyl, R7=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means m-CO N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means m-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means on-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=p-ethoxycarbonylpyrimidine, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means m-CO2N-p-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=4'-aminosulphonylphenyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=4'-(2"-pyrimidinyl idealfor)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3means m-HE-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3means on-HE-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=p-ethoxycarbonylpyrimidine, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=m-HE-p-CO2N-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=m-CO2N-p-HE-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3means m-CF3-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=4'-aminosulphonylphenyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3means 4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3means p-CO2N-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=Co3, R8=NO2;
R3means p-HE-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=Co3, R8=NO2;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=C2H5, R7=Co3, R8=NO2;
R3=p-ethoxycarbonylpyrimidine, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=C2H5, R7=OCH3R8=NO2;
R3=p-CO2H-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=o-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3 ;
R3means p-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means m-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means on-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=p-ethoxycarbonylpyrimidine, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=m-HE-p-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=m-CO2N-p-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=4'-aminosulphonylphenyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=4'-(2'what-pyrimidinemethanol)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means o-CO2N-p-iodinization, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3means p-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means m-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means o-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means p-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means m-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means on-HE-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6 =NO2, R7=OCH3, R8=CH3;
R3=p-ethoxycarbonylpyrimidine, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means m-CF3-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means m-CF3-p-NR2-phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3,
R8=CH3;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=NO2, R7=OCH3,
R8=CH3;
R3=4'-aminosulphonylphenyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl,
R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3means p-CO2N-phenylenecarbonyl, R4= 5=H, R6=R8=NO2, R7=OH;
R3means p-HE-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3means m-HE-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3means on-HE-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3=p-ethoxycarbonylmethylene, R4=R5=H, R6=R8=NO2, R7=OH;
R3means CF3-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3=4'-aminosulphonylphenyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=R8=NO2, R7=OH;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3=4'-(5",6"-dimethoxypyrimidine-4"-aminosulfonyl)phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3means of With the 2N-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3means p-HE-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3=p-ethoxycarbonylmethylene, R4=R5=H, R6=R8=NO2, R7=OH;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=R8=NO2, R7=OH;
R3means p-och3-phenylenecarbonyl, R4=R5=H, R6=Cl, R7=OH, R8=NO2;
R3=4'-guanidinonaltrindole, R4=R5=H, R6=Cl, R7=OH, R8=NO2;
R3means m-HE-p-CO2N-phenylenecarbonyl, R4=H, R5=CH3, R6=Cl, R7=OH, R8=NO2;
R3means p-CO2N-phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3means m-CO2N-phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3means o-CO2N-phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3means p-och3-phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3=p-ethoxycarbonylpyrimidine, R4=H, R5=CH 3
, R7=OH, R6=R8=NO2;
R3=p-aminosulphonylphenyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3=p-guanidinonaltrindole, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3=4'-(2"-pyrimidinemethanol)phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3=4'-(2"-thiazoleethanol)phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3=4'-(4",6"-dimethylpyrimidine-2"-aminosulfonyl)phenylenecarbonyl, R4=H, R5=CH3, R7=OH, R6=R8=NO2;
R3means CONH(CH3) COOH, R4=R5=R6=R8=H, R7=OCH3;

R3=,R4=R5=R6=R8=H, R7=OCH3;
R3=,R4=R5=R6=R8=H, R7=OCH3;
R3=,R4=R5=R 6=R8=H, R7=OCH3;
R3means CONH(CH3)COOH, R4=R5=R8=H, R5=C2H5, R7=OCH3;
R3=,R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=,R4=R5=R8=H, R6=C2H5, R7=OCH3;
R3=,R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=,R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=,R4=R6=R8=H, R5=CH3, R7=OCH3;
R3=,R4=R6=R8=H, R5=CH37=Co3;
R3=,R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=,R4=R5=R6=H, R7=OCH3, R8=CH3;

R3=,R4=R5=R6=H, R7=OCH3, R8=CH3;
R3=,R4=R5=R8=H, R6=Br, R7=OCH3;
R3=,R4=R5=R8=H, R6=Br, R7=OCH3,
R3=,R4=R5=R8=H, R6=Br, R7=OCH3;
R3=,R4=R5 =R8=H, R6=hexyl, R7=OCH3;
R3=,R4=R5=R8=H, R6=hexyl, R7=OCH3;
R3=,R4=R5=R8=H, R6=hexyl, R7=OCH3;
R3=,R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=,R4=R5=H, R6=NO2, R7=OCH3, R8=CH3;
R3=,R4=R5=H, R6=NO2, R7=R8=OCH2;
R3=,R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=CO2C2H5, R4=R5=H, R6=NO, R7=R8=OCH3/sub> ;
R3=CO2H, R4=R5=H, R6=NO2, R7=R8=OCH3;
R3=CO2C2H5, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=CO2H, R4=R5=H, R6=NO2, R7=OH, R8=CH3;
R3=CO2C2H5, R4=R5=H, R6=NH2, R7=OH, R8=CH3;
R3=CO2H, R4=R5=H, R6=NO2, R7=OCH3, R8=CH3

R3=CO2C2H5, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=CO2H, R4=R5=H, R6=C2H5, R7=OH, R8=NO2;
R3=CO2C2H5, R4=R5=H, R6=C2H5, R7=OCH3, R8=NO2;
R3=CO2H, R4=R5=H, R6=C2H5 , R7=OH, R8=NO2;
R3=CO2C2H5, R4=R5=H, R6=R8=NO2, R7=OH;
R3=CO2H, R4=R5=H, R6=R8=NO2, R7=OH,
R3=CO2C2H5, R4=R5=H, R6=R8=NO2, R7=OCH3;
R3=CO2H, R4=R5=H, R6=R8=NO2, R7=OCH3;
R3=CO2C2H5, R4=R5=H, R6=Cl, R7=OH, R8=NO2;
R3=CO2H, R4=R5=H, R6=Cl, R7=OH, R8=NO2;
R3=CO2H, R4=H, R5=CH3, R6=R8=NO2, R7=OH;
R3=CO2C2H5, R4=H, R5=CH3, R6=R8=NO2, R7=OH;
R4=,R3=R5=R6=R8=H, R7=CH3;
R4=,R3=R5=R6=R8=H, R7=CH3;
R4=,R3=R5=R6=R8=H, R7=CH3;
R3=R5=R6=R8=HR4=CH3R7=;
R3=R5=R6=R8=HR4=CH3R7=;
R3=R5=R6=R8=HR4=CH3R7=;
R3=R5=R6=R8=HR4=CH3R7=;
R4=CH3R7=;
R3=R5=R6=R8=HR4=CH3R7=;

R3=R5=R6=R8=HR4=CH3R7=;
R3=R5=R6=R8=HR4=CH3R7=
R3=R5=R6=R8=HR4=CH3R7=
R3=R5=R6=R8=HR4=CH3R7=;
R3= 5=R6=R8=HR4=CH3R7=;
R3=R5=R6=R8=HR4=CH3R7=
R3=R5=R6=R8=HR4=CH3R7=
R3=R5=R6=R8=HR4=CH3R7=
R3=R5=R6=HR4=R8=CH3R7=;
R3=R5=R6=HR4=R8=CH3R7=
R3=R5=R4=HR4=R8=CH3R7
R3=R4=R5=R7=R8=HR6=;
R3=R4=R5=R7=R8=HR6=.

6. The compound according to claim 1, characterized in that the compound includes pharmaceutically acceptable salts and hydrates or esters.

7. Method of preparing compounds according to any one of claims 1 to 6, comprising the reaction of condensation of 3-carboxy-, 4-carboxy-, 6-carboxy-coumarin or 7-carboxymethoxy is a derivative of coumarin with the appropriate substituted amine or hydrazine and the amidation process, and reagents for the amidation process selected from the group consisting of trichloride phosphorus oxychloride phosphorus, pentachloride phosphorus, thionyl chloride, 1,3-dicyclohexylcarbodiimide, piperidinylcarbonyl (2-DPC), 1,3-diisopropylcarbodiimide (DIPC) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI)and used in a method of catalytic agents are selected from tertiary amines, pyridine, 4-dimethylaminopyridine and personalkristine, and preferably used in the method of organic solvents on the given sulfoxide, toluene, dichloromethane, 1,2-dichloroethane, dimethyl ether of ethylene glycol, tetrahydrofuran, and N,N-dimethylformamide.

8. The method according to claim 7, in which 3-carboxy-, 4-carboxy-, 6-carboxy-coumarin or 7 - carboxymethoxy-coumarin derivative is condensed with the appropriate substituted hydrazine followed by cyclization of the thus obtained hydrazide to form heterocyclic derivative.

9. Pharmaceutical composition having inhibitory activity against transforming growth factor β1(TGF-β1), containing a pharmaceutically effective dose of a compound according to any one of claims 1 to 6 and a pharmaceutically acceptable carrier.

10. The composition according to claim 9 in the form of tablets, capsules, pill, aerosol, injection, drug delayed release, controlled release, or in the form of a supply system of small particles.

11. The use of compounds according to any one of claims 1 to 6 to obtain inhibitors of the transforming growth factor β1(TGF-β1).

12. The use of compounds according to any one of claims 1 to 6 to obtain antagonists enzyme that turns the receptor of angiotensin II (AngII).

13. The use of compounds according to any one of claims 1 to 6 to obtain drugs for the treatment of chronic renal disorders.

14. The use of compounds according to any one of claims 1 to 6 to obtain a drug is drugs for the treatment of cardio-cerebral-vascular diseases.
15 the Use of compounds according to any one of claims 1 to 6 to obtain drugs for the treatment of ainsliezubaida diabetes.

16. The application 14, in which these cardio-cerebral-vascular diseases are hypertension, cerebral and coronary embolism, myocardial infarction, stroke, apoplectically kick and their complications.

17. The use of compounds according to any one of claims 1 to 6 to obtain drugs for treatment or prevention of cancer and precancerous lesions.



 

Same patents:

FIELD: chemistry; medicine.

SUBSTANCE: invention relates to 3-phenylpropionic acid derivatives of formula (I) as ligand of peroxisome proliferator-activated gamma-receptor (PPARγ), to their pharmaceutically acceptable salts, as well as to their application, treatment method and based on them pharmaceutical composition. Compounds can be applied for treatment and prevention of diseases mediated by peroxisome proliferator-activated gamma-receptor (PPARγ), for instance type 2 diabetes, insulin-resistance, metabolic syndrome, complications resulting from or connected with diabetes, cardio-vascular dysfunctions, atherosclerosis, obesity, cognition disturbances and lipid metabolism derangements. In general formula (I): W represents COOH or -COO-C1 - C4-alkyl group; Y represents NH; Z represents S or O; X represents O; R1 - R8 each independently represents hydrogen atom or halogen atom; A represents mono-, bi- or tri-cyclic 5-13-member heteroaryl with 1 or 2 heteroatoms selected from N, S or O, aryl, selected from phenyl and naphtyl, or -N(C1-C4-alkyl)-CO-C3-C7-cycloalkyl, where heteroaryl is optionally substituted with 1-3 substituents, independently selected from group, consisting of C1-C4-alkyl, CN, phenyl halogen and phenyl, optionally substituted with 1-3 substituents, independently selected from C1-C4alkoxy, halogen and ethylenedioxy-group; and n represents integer number from 0 to 3 including; and their pharmaceutically acceptable salts.

EFFECT: increased efficiency of composition and treatment method.

20 cl, 14 dwg, 10 ex

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 ex

FIELD: chemistry.

SUBSTANCE: invention can be applied in medicine and concerns inhibitors of MaR-kinase p38 of formula where W represents N or O, when Y represents C, and W represents C, when Y represents N; U represents CH or N; V represents C-E or N; X represents O, S, SO, SO2, NH, C=O,-C=NOR1 or CHOR1; B represents H or NH2; R1, E and A stands for H or various alkyl, heteroalkyl, aromatic and heteroaromatic substitutes.

EFFECT: production of new biologically active compounds.

48 cl, 138 ex, 54 dwg

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (I) where R1 stands for hydrogen or linear, branched, saturated or unsaturated hydrocarbon radical; D stands for nitrogen atom or C-R2; E stands for nitrogen atom or C-R3; F stands for nitrogen atom or C-R4; G stands for nitrogen atom or C-R5; R2, R3, R4 and R5 are identical or different and individually represent hydrogen, halogen, alkoxy, linear or branched, saturated or unsaturated hydrocarbon radical; W stands for oxygen atom; X stands for radical of formula radical -(CH2)k-C(O)-(CH2)m-, -(CH2)n- or -(CH2)r-O-(CH2)s-, where k, m, r and s are equal to integers 0 to 6, and n is equal to an integer 1 to 6. Said radicals are optionally substituted with one or more substitutes independently chosen from the group consisting of R7; Y stands for radical of formula radical -(CH2)i-NH-C(O)-(CH2)j-, -(CH2)n-, -(CH2)r-O-(CH2)s-, -(CH2)t-NH-(CH2)u-, where i, j, n, r, s, t and u are equal to integers 0 to 6. Said radicals are optionally substituted C1-3alkyl, or C1-3alkyl-C1-3alkylsulphonylamino; radicals R7, B, R8, A, R9 are as it is presented in the patent claim. The invention also describes the pharmaceutical composition possessing inhibitory activity of receptor tyrosine kinase to KDR receptor including described compounds.

EFFECT: compounds possess inhibitory activity of receptor tyrosine kinase to KDR receptor and can be effective in therapy of the diseases associated uncontrolled angiogenesis.

29 cl, 746 ex, 6 tbl

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to novel 2,4-pyridindiamine compounds of formula (1). In structural formula (I) L1 is direct bond; L2 is direct bond; R2 is phenyl group, three times substituted with three groups R8; R4 is X represents N; Y is selected from group consisting of O, NH, S, SO and SO2; Z is selected from group consisting of O, NH; on condition that if Y is selected from group consisting of NH, S, SO and SO2, Z is not the same as Y; R5 is selected from group consisting from R6, halogen; each R6 is independently selected from group consisting of hydrogen, halogen; R8 is selected from group consisting from Ra, Rb, Ra substituted with one or several similar or different groups Ra or Rb, -ORa, -O-CHRaRb; each R35 independently on others is selected from group consisting of hydrogen and R35, or in alternative case, two groups R35, bound to one and the same carbon atom are taken together with formation of oxogroup (=O), and the remaining two groups R35 each independently on each other are selected from group consisting from hydrogen and R8; each Ra is independently selected from group consisting of hydrogen, (C1-C6) alkyl, (C3-C8) cycloalkyl; each Rb is suitable group which is independently selected from group consisting of -ORd, halogen, -CF3, -C(O)NRcRc, and -OC(O)ORd; each Rc is independently protective group or Ra; each Rd is independently protective group or Ra; each index m is independently integer number from 1 to 3.

EFFECT: novel compounds can be used for treatment or prevention of autoimmune diseases, for instance such as rheumatoid arthritis and/or related to it symptoms, systemic lupus erythematosus and/or related to it symptoms, as well as and/or related to it symptoms.

41 cl, 14 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel compounds of formula I: , where M is macrolide subunit of substructure II: , L is chain of substructure III: -X1-(CH2)m-Q-(CH2)n-X2-, D is steroid or non-steroid subunit derived from steroid or non-steroid NSAID medicines (nonsteroid anti-inflammatory drug) with anti-inflammatory effect; pharmaceutically acceptable salts and solvates of claimed compounds; methods and intermediary compounds for obtainment of claimed compounds.

EFFECT: improved therapeutic effect, application in inflammatory disease and state treatment for humans and animals.

37 cl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compound represented by formula I, where R1 and R2 are similar or different and each represents: (I) C1-10alkyl group optionally substituted with 1-3 substituents selected from C3-10cycloalkyl group, C1-6alkoxycarbonyl group b C1-6alkoxygroup; (2) C6-14aryl group optionally substituted with 1-3 substituents selected from halogen atom, carboxyl group, C1-6alkoxycabonyl group b carbamoyl group; or (3) C7-13aralkyl group; R3 represents C6-14aryl group optionally substituted with 1-3 substituents selected from C1-6alkyl group, optionally substituted with 1-3 halogen atoms, halogen atom, C1-6alkoxycarbonyl group, carboxyl group, hydroxy group, C1-6alkoxygroup, optionally substituted with 1-3 halogen atoms; R4 represents amino group; L represents C1-10alkylene group; Q represents bond, C1-10alkylene group or C2-10alkenylene group; and X represents: (1) hydrogen atom; (2) cyanogroup; (3) (3a) carboxyl group; (3b) carbamoyl group; and further as presented in invention formula. Invention also describes medication for treating diabetes, peptidase inhibitor, application of formula I compound, method of prevention or treatment of diabetes, method of peptidase inhibiting and method of obtaining formula I compounds.

EFFECT: obtaining novel compounds which have peptidase-inhibiting activity and are useful as medication for prevention and treatment of diabetes.

16 cl, 433 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: described is novel compound of formula (I)

or its pharmaceutically acceptable salt, values of radicals are given in invention formula Compound has ability to inhibit receptor mGluR5, which intends it for prevention and/or treatment of receptor mGluR5- associated disturbances. Also described is pharmaceutical composition, method of inhibiting activation of receptors mGluR5, using compound of formula (I). Described is method of obtaining compound of formula 1a or 1b structure.

EFFECT: increasing output of suitable product.

18 cl, 825 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new 2-pyridone derivatives of formula (I): where R1, R2, R4, R5, G1, G2, L, Y and n are as specified in the invention formula, and their pharmaceutically acceptable salts, pharmaceutical compositions containing these compounds, and their application in therapy. These compounds have neutrophil elastase inhibition effect.

EFFECT: new compounds with useful biological properties.

7 cl, 1 tbl, 150 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine derivatives with general formula (I), their tautomeric or stereoisomeric form, in free form, in form of pharmaceutically acceptable salt or C1-6alkyl ester which are effective antagonists of CRTH2 (G-protein-associated chemoattractant receptor, ex prone on Th2 cells) and can be used for preventing and treating diseases related to CRTH2 activity, particularly in treatment of allergic diseases such as asthma, allergic rhinitis, atopic dermatitis, diseases related to eosinophil. In formula (I) R1 is hydrogen, or in which n is an integer from 0 to 6; -Q1- is -NH-, -N(C1-6alkyl)- or -O; Y is hydrogen, C1-6alkyl, C3-6cycloalkyl, optionally substituted with C1-6alkyl, C3-6cycloalkyl, condensed with a benzene ring, phenyl, naphthyl or 5-6-member heteroaryl, possibly condensed with a benzene ring, and containing at least one heteroatom, chosen from a group consisting of oxygen and nitrogen, where the said phenyl, naphthyl or heteroaryl are optionally substituted on the displaceable position with one or several substitutes, chosen from a group consisting of cyano, halogen, nitro, guanidine, pyrroyl, sulfamoyl, phenyloxy, phenyl, di(C1-6)alkylamino, C1-6alkanoylamino, C1-6alkyl, optionally mono-, di- or tri-substituted with halogen, C1-6alkoxy, optionally mono-, di- or tri-substituted with halogen and C1-6alkylthio, optionally mono-, di- or tri-substituted with halogen; or phenyl, condensed with 1,3-dioxolane; R2 is hydrogen or C1-6alkyl; R3 is a halogen, C1-6alkoxy, optionally mono-, di- or tri-substituted with halogen, or , R3a and R3b are independently C3-8cycloalkyl or C1-6alkyl, this C1-6alkyl is optionally substituted with hydroxyl, carboxy, C3-6cycloalkylcarbamoyl, C5-6heterocyclocarbonyl containing a heteroatom in form of nitrogen, or C1-6alkoxy, q is an integer from 1 to 3; R3c is hydrogen, hydroxyl or carboxy; Xa is -O-; R4 is hydrogen, halogen, di(C1-6alkyl) amino or C1-6alkyl, optionally substituted C1-6alkoxy or mono- , di- or tri-substituted with halogen; R5 is hydrogen or C1-6alkyl; and R6 is carboxy, carboxamide, nitrile or tetrazolyl.

EFFECT: wider field of use of compounds.

32 cl, 9 tbl, 13 ex

FIELD: chemistry.

SUBSTANCE: invention is related to the compound of general formula 1 or its tautomer or pharmaceutically acceptable salt, where W selected from N and CR4; X is selected from CH(R8), O, S, N(R8), C(=O), C(=O)O, C(=O)N(R8), OC(=O), N(R8)C(=O), C(R8)-CH and C(=R8); G1 - bicyclic or tricyclic condensed derivative of azepin, selected from general formulas 2-9 , or derivative of aniline of common formula 10 , where A1, A4, A7 and A10 are independently selected from CH2, C=O, O and NR10; A2, A3, A9, A11, A13, A14, A15, A19 and A20 are independently selected from CH and N; or A5 stands for covalent connection, and A6 represents S; or A5 stands for N=CH, and A6 represents covalent connection; A8 , A12 , A18 and A21 are independently selected from CH=CH, NH, NCH3 and S; A16 and A17 both represent CH2, or one from A16 and A17 represents CH2, and the one another is selected from C=O, CH(OH), CF2, O, SOc and NR10; Y is selected from CH=CH or S; R1 and R2 are independently selected from H, F, Cl, Br, alkyl, CF3 and group O-alkyl; R3 is selected from H and alkyl; R4-R7 are independently selected from H, F, Cl, Br, alkyl, CF3, OH and group O-alkyl; R8 is selected from H, (CH2)bR9 and (C=O)(CH2)bR9; R9 is selected from H, alkyl, possibly substituted aryl, possibly substituted heteroaryl, OH, groups O-alkyl, OC(=O)alkyl, NH2, NHalkyl, N(alkyl)2, CHO, CO2H, CO2alkyl, CONH2, CONHalkyl, CON(alkyl)2 and CN; R10 is selected from H, alkyl, group COalkyl and (CH2)dOH; R11 is selected from alkyl, (CH2)dAr, (CH2)dOH, (CH2)dNH2, group (CH2)aCOOalkyl, (CH2)dCOOH and (CH2)dOAr; R12 and R13 are independently selected from H, alkyl, F, CI, Br, CH(OCH3)2, CHF2, CF3, groups COOalkyl, CONHalkyl, (CH2)dNHCH2Ar, CON(alkyl)2, CHO, COOH, (CH2)dOH, (CH2)dNH2, N(alkyl)2, CONH(CH2)dAr and Ar; Ar is selected from possibly substituted heterocycles or possibly substituted phenyl; a is selected from 1, 2 and 3; b is selected from 1, 2, 3 and 4; c is selected from 0, 1 and 2; and d is selected from 0, 1, 2 and 3. Besides, the invention is related to pharmaceutical compound and to method for activation of vasopressin receptors of type 2.

EFFECT: compounds according to invention represent agonists of receptor of vasopressin V2, which stipulates for their application (another object of invention) for preparation of medicine for treatment of condition selected from polyuria, including polyuria, which is due to central diabetes insipidus, nocturnal enuresis of nocturnal polyurea, for control of enuresis, to postpone bladder emptying and for treatment of disorders related to bleeds.

21 cl, 228 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new nitroxide compounds with formula I: where one of A, B and D represents N-O and others represent CR6; R1 represents alkyl, containing 1 to 4 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; R2 represents alkyl, containing 1 to 12 carbon atoms, which is branched or straight and which is unsubstituted or substituted once or several times with a halogen; cycloalkylalkylk, containing 3 to 10 carbon atoms, which is unsubstituted or substituted once or several times with oxo, aryl, containing 6 to 14 carbon atoms, which is unsubstituted or substituted once or several times with OCF3; or a heterocyclic group, which is saturated, partially saturated or unsaturated, with 5 to 10 atoms in the ring, where at least 1 atom in the ring is an atom of N, O, or S; R3 represents cycloalkyl, containing 3 to 10 carbon atoms, which is unsubstituted once or several times with oxo, aryl, containing from 6 to 14 carbon atoms or which is unsubstituted or substituted once or several times with OCF3; or heteroaryl, with 5 to 10 atoms in the ring, in which at least 1 atom in the ring is a heteroatom; R represents H or alkyl, containing 1 to 4 carbon atoms. The invention also relates to pharmaceutically used salts of these compounds, pharmaceutical compositions containing these compounds, method of inhibiting PDE4 enzyme and to methods treatment using these compounds.

EFFECT: new compounds with useful biological properties.

62 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel amidomethyl-substituted derivatives of 2-(4-sulfonylamino)-3-hydroxy3,4-dihydro-2N-chromen-6-yl of the general formula (I) where R1 is C1-C4alkyl, R2 is C1-C4alkyl, R3 is phenyl optionally once or twice substituted or substituted by halogen, C1-C4alkyl, C1-C4alkoxy group or trifluoromethyl, naphthyl or biphenyl, R4 is hydrogen, C1-C6alkyl or C3-C7cycloalkyl-C1-C4alkyl, R5 is hydrogen, and R6 is C1-C6 alkyl, phenyl-C1-C4alkyl, phenyl group optionally substituted by halogen, furyl-C1-C4alkyl or tetrahydronaphthyl, or R5 and R6 together with nitrogen atom linking them form piperazine ring optionally substituted by phenyl.

EFFECT: also invention claims method of obtaining claimed compounds, and intermediary products used in method implementation, as well as medicines containing compounds of the formula (I) with antiarrhythmic effect, and application of these medicines.

11 cl, 6 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention describes novel compound represented by formula I, where R1 and R2 are similar or different and each represents: (I) C1-10alkyl group optionally substituted with 1-3 substituents selected from C3-10cycloalkyl group, C1-6alkoxycarbonyl group b C1-6alkoxygroup; (2) C6-14aryl group optionally substituted with 1-3 substituents selected from halogen atom, carboxyl group, C1-6alkoxycabonyl group b carbamoyl group; or (3) C7-13aralkyl group; R3 represents C6-14aryl group optionally substituted with 1-3 substituents selected from C1-6alkyl group, optionally substituted with 1-3 halogen atoms, halogen atom, C1-6alkoxycarbonyl group, carboxyl group, hydroxy group, C1-6alkoxygroup, optionally substituted with 1-3 halogen atoms; R4 represents amino group; L represents C1-10alkylene group; Q represents bond, C1-10alkylene group or C2-10alkenylene group; and X represents: (1) hydrogen atom; (2) cyanogroup; (3) (3a) carboxyl group; (3b) carbamoyl group; and further as presented in invention formula. Invention also describes medication for treating diabetes, peptidase inhibitor, application of formula I compound, method of prevention or treatment of diabetes, method of peptidase inhibiting and method of obtaining formula I compounds.

EFFECT: obtaining novel compounds which have peptidase-inhibiting activity and are useful as medication for prevention and treatment of diabetes.

16 cl, 433 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention concerns new 2-pyridone derivatives of formula (I): where R1, R2, R4, R5, G1, G2, L, Y and n are as specified in the invention formula, and their pharmaceutically acceptable salts, pharmaceutical compositions containing these compounds, and their application in therapy. These compounds have neutrophil elastase inhibition effect.

EFFECT: new compounds with useful biological properties.

7 cl, 1 tbl, 150 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to application of indazole derivatives of general formula (I) , in which: R stands for O; R3 stands for radical (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, said radicals being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R4, R5, R6 and R7, independently on each other are selected from following radicals; hydrogen atom, halogen, CN, NO2, NH2, NHSO2R9, trifluoromethyl, trifluoromethoxygroup, (C1-C6)-alkyl, phenyl, phenyl-(C1-C6)-alkyl, pyridyl, possibly substituted with amino or hydroxygroup, thienyl, furanyl, morpholino, phenyl being unsubstituted or substituted with one or several substitutes, given in item 1 of the formula; R8, R9, R10, R11, independently on each other, stand for hydrogen atom, (C1-C6)-alkyl, phenyl possibly substituted with halogen; their racemates, enantiomers, diastereoisomers and their mixtures, their tautomers and their pharmaceutically acceptable salts for obtaining medication, inhibiting phosphorylation of Tau-protein. Invention also relates to novel compounds of formula (I), particular indazole derivatives, their racemates, enantiomers, tautomers and pharmaceutically acceptable salts, pharmaceutical composition and based on them medication which inhibits Tau-protein phosphorylation, as well as to method of obtaining compounds of formula (I).

EFFECT: obtaining medication based on indazole derivatives, inhibiting Tau-protein phosphorylation.

9 cl, 118 ex, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention concerns to new diamides of pyrimidine-4,6-dicarboxylic acid of I formula, selective inhibitors of collagenases possessing properties which concern to the metalloproteinase superfamily and the matrix metalloproteinases. The bonds render influence on hyperactivity of the matrix metalloproteinase-13 (MMP-13) and thus do not render influence on MMP-3 and MMP-8. In the formula I R1 means an atom of hydrogen, R2 means - (C1-C6)-alkyl where alkyl is unitary replaced by phenyl where phenyl is replaced 1) -(C0-C6)-alkyl-C(O)-N(R9)-(R10), where R9 and R10 identical or different and independently from each other mean i) atom of hydrogen or ii) - (C1-C6)-alkyl or R9 and R10 together with atom of nitrogen to which they are bound, form 5, 6-links the sated cycle, and instead of one or two other atoms of carbon there can be also a heteroatom from an oxygen row, sulphur and nitrogen, and in case of nitrogen atoms of nitrogen independently from each other can be unsubstituted or substituted with (C1-C6)-alkyl, 2) -(C0-C6)-alkyl-C(O)-NH-SN, 3) -O-(C0-C6)-alkyl-C(O)-N(R9)-(R10) where R9 and R10 have the specified above value, 4) -(C0-C6)-alkyl-C(O)-N (R8)-(C0-C6)-alkyl-N(R9)-(R10) where R8 means hydrogen, R9 and R10 have the specified above value, 5) -(C0-C6)-alkyl-C(O)-N(R8)-(C0-C6)-alkyl-Het, and R8 has the specified above value, and Het means the sated or nonsaturated monocyclic heterocyclic system with number of links from 3 to 6 which contains in a cycle of 1 or 2 identical or different heteroatoms from a number nitrogen, oxygen and sulphur and unsubstituted or one-, two- or triple independently from each other is replaced by halogen, b) hydroxy,) -(C1-C6)-alkyl, and alkyl is unsubstituted or one-, two- or triple is substituted by halogen, d)=0,e)-Het, R4 and R5 or R5 and R6 together with atom of Carboneum to which they are bound, independently from each other form 5 or 6-unit cycle which is sated and contains one or two heteroatoms from an oxygen row.

EFFECT: obtaining of bonds which can find application for treatment of degenerate diseases of joints, such as osteoarthritis, rheumatic disease.

7 cl, 3 tbl, 117 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to water-free crystalline form 6-[[(3S,4R)-3,4-dihydro-3-hydroxi-6-[(3-hydroxiphenyl)sulfonyl]-2,2,3-trimethyl-2H-1-benzopyrane-4-yl]oxy]-2-methyl-3(2H)-pyridasinon, whose powder radiograph is in fact similar to radiograph, presented in Figure I, and on which there is at least one characteristic pinnacle with approximate values 2θ, selected from group, which consists of 10.5°, 15.0°, 17.2° and 22.8°, a well as to method of obtaining it and method of hair growing stimulation by introducing composition which is based on said crystalline form into mammal.

EFFECT: obtaining effective means, which stimulate hair growing.

9 cl, 8 dwg, 4 ex

FIELD: chemistry, pharmacology.

SUBSTANCE: invention relates to novel compounds of formula (I), its pharmaceutically acceptable salts, possessing qualities of chemokine receptor modulators. Compounds can be applied for asthma, allergic rhinitis, COLD, inflammatory intestinal disease, irritated intestine syndrome, osteoarthritis, osteoporosis, rheumatoid arthritis, psoriasis or cancer. In compound of formula (I) , R1 represents group selected from C1-8alkyl, said group is possibly substituted with 1, 2 or 3 substituents, independently selected from -OR4 , -NR5R6 , phenyl, phenyl is possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4,-NR5R6,-SR10,C1-6alkyl and trifluoromethyl; R2 represents group selected from C1-8alkyl, said group is substituted with 1, 2 or 3 substituents, independently selected from hydroxy, amino, C1-6alkoxy, C1-6alkylamino, di(C1-6alkyl)amino, N-(C1-6alkyl)-N-(phenyl)amino; R3 represents hydrogen, R4 represents hydrogen or group selected from C1-6alkyl and phenyl, R5 and R6, independently, represent hydrogen or group selected from C1-6alkyl and phenyl, said group being probably substituted with 1, 2 or 3 substituents, independently selected from -OR14, -NR15R16, -COOR14,-CONR15R16, or R5 and R6 together with nitrogen atom, to which they are bound, form 4-7-member saturated heterocyclic ring system, possibly containing additional heteroatom, selected from oxygen and nitrogen atoms, ring possibly being substituted with 1, 2 or 3 substituents, independently selected from -OR14, -COOR14,-NR15R16,CONR15R16 and C1-6alkyl; R10 represents hydrogen or group selected from C1-6alkyl or phenyl; and each from R7, R8, R9, R14, R15, R16 independently represents hydrogen, C1-6alkyl or phenyl; X represents hydrogen, halogeno; Rx represents trifluoromethyl, -NR5 R6 , phenyl, naphtyl, heteroaryl, heteroring can be partly or fully saturated, and one or more ring carbon atoms can form carbonyl group, each phenyl or heteroaryl group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, cyano, -OR4, -NR5R6, -CONR5R6, -COR7, -COOR7, -NR8COR9, -SR10, -SO2R10, -SO2NR5R6, -NR8SO2R9, C1-6alkyl or trifluoromethyl; or Rx represents group selected from C1-6alkyl, said group being possibly substituted with 1, 2 or 3 substituents, independently selected from halogeno, -OR4, -NR5R6, phenyl or heteroaryl, where heteroaryl represents monocyclic or bicyclic aryl ring, containing from 5 to 10 ring atoms, from which 1, 2 or 3 ring atoms are selected from nitrogen, sulfur or oxygen. Invention also relates to methods of obtaining compounds, versions, pharmaceutical composition and application for manufacturing medications using compounds of invention.

EFFECT: obtaining novel compounds of formula (I), its pharmaceutically acceptable salts, possessing properties of chemokine receptor moduators.

25 cl, 138 ex

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