Derivatives of oxazolidine antibiotics

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula I in which R1 represents halogen, methoxy group or cyano group; each of Y1 and Y2 represents CH, and one or two from U, V, W and X represent N, and each remaining one represents CH, or in case X, cam also represent CRa, or Ra represents halogen; A represents CH2CH(OH), CH2CH(NH2), CH(OH)CH(NH2) or CH(NH2)CH2, B represents CH2CH2, CH2NH or CONH, and D represents CH2, or A represents CH(OH)CH2, and B represents CH2NH, N(R2)CO or CONH, and D represents CH2, or B represents N(R2a)CH2, and D represents CH(OH), or A represents CH(OH)CH(OH), B represents CH2NH or CONH and D represents CH2, or A represents CH2CH2, and B represents CH2CH2, CH2NR3, NHCO, CONR4, CH2O, COCH2 or CH2CH2NH, and D represents CH2, or B represents CH2NH, and D represents CO, or A also represents CH2CH2, B represents NR4bCH2 and D represents CH(OH), or A represents CH=CH, B represents CH2NR5 or CONR6, and D represents CH2, or A represents C≡C, B represents CH2NH and D represents CO, or A represents COCH2, B represents CONH and D represents CH2, or A represents CH2N(R7), and B represents CH2CH2, a D represents CH2, or B represents CH2CH(OH), a D represents CH(OH), or A represents NHCH2, and B represents CH2NH, a D represents CH2, or B represents CH2NH, a D represents CO, or A represents NHCO, B represents CH(R8)NH or CH2CH2, and D represents CH2, or A represents OCH2, B represents CH=CH or CONH, and D represents CH2; R2 represents (C1-C4)alkyl; R2a represents hydrogen; R3 represents hydrogen, CO-(CH2)p-COOR3', (CH2)p-COOR3, (C2-C5)acyl or amino(C1-C4)alkyl, or also R3 represents (C1-C4)alkyl, which can be one or two times substituted with hydroxygroup, p stands for integer number from 1 to 4, and R3 represents hydrogen or (C1-C4)alkyl; R4 represents hydrogen or (C1-C4)alkyl; R4b represents hydrogen; R5 represents hydrogen or (C2-C5)acyl; R6 represents hydrogen or (C1-C4)alkyl; R7 represents hydrogen or (C1-C4)alkyl, which can be one or two times substituted with group, independently selected from hydroxygroup and aminogroup, R8 represents hydrogen or (C1-C4)alkyl; E represents one of the following groups (a-a1) where Z represents CH or N, and Q represents O or S, or E represents phenyl group, which is one or two times substituted in meta- and/or para-position with substituents, each of which is independently selected from group, including halogen, (C1-C3)alkyl and trifluoromethyl; or pharmaceutically acceptable salt of such compound. Formula I compound or its pharmaceutically acceptable salt is applied for obtaining medication or pharmaceutical composition for prevention or treatment of bacterial infection.

EFFECT: derivatives of oxazolidine antibiotics for obtaining medication for treatment of bacterial infections.

15 cl, 2 tbl, 214 ex

 

The text descriptions are given in facsimile form.

1. The compound of the formula I

in which
R1represents a halogen, a methoxy group or a cyano;
each of the Y1and Y2represents CH, and one or two of U, V, W and X are N, and each of the remaining represents CH, or in the case of X, may also represent a CRaor
Rais a halogen;
And represents CH2CH(OH), CH2CH(NH2), CH(OH)CH(NH2) or CH(NH2)CH2In represents CH2CH2CH2NH or CONH and D is CH2or
And represents the CH(OH)CH2and represents CH2NH, N(R2)CO or CONH and D is CH2or represents-N(R2a)CH2and D is CH(OH), or
And represents the CH(OH)CH(OH), is a CH2NH or CONH and D is CH2or
And represents CH2CH2and represents CH2CH2CH2NR3, NHCO, CONR4CH2O COCH2or CH2CH2NH, and D represents CH2or p is ecstasy a CH 2NH, and D is CO, or a is a CH2CH2In represents NR4bCH2and D is CH(OH), or
And represents CH=CH, A represents CH2NR5or CONR6and D represents CH2or
But a With a≡C, b represents CH2NH and D represents CO or
And is a COCH2In represents CONH and D is CH2or
And represents CH2N(R7), and represents CH2CH2and D represents CH2or represents CH2CH(OH), D represents CH(OH), or
But is NHCH2and represents CH2NH, and D represents CH2or represents CH2NH, and D represents CO or
And represents NHCO, represents CH(R8)NH or CH2CH2and D represents CH2or
And represents OCH2In represents CH=CH or CONH and D is CH2;
R2is a (C1-C4)alkyl;
R2arepresents hydrogen;
R3represents hydrogen, CO-(CH2)p-COOR3', (CH2)p-COOR3', (C2-C5)acyl or amino(C1-C4)alkyl, or R3predstavljaet a (C 1-C4)alkyl, which may be one or two times substituted by a hydroxy-group, p denotes an integer from 1 to 4, and R3'represents hydrogen or (C1-C4)alkyl;
R4represents hydrogen or (C1-C4)alkyl;
R4brepresents hydrogen;
R5represents hydrogen or (C2-C5)acyl;
R6represents hydrogen or (C1-C4)alkyl;
R7represents hydrogen or (C1-C4)alkyl, which may be one or two times substituted by groups independently selected from hydroxy-group and amino group,
R8represents hydrogen or (C1-C4)alkyl;
E represents one of the following groups:

where Z represents CH or N, and Q represents O or S, or
E represents a phenyl group, which is once or twice substituted in the meta and/or para-position substituents, each of which is independently selected from the group comprising halogen, (C1-C3)alkyl and trifluoromethyl;
or pharmaceutically acceptable salt of such compounds.

2. The compound of formula I according to claim 1, which is a compound of formula ICE

where R1represents a halogen, a methoxy group is whether the cyano;
each of the Y1, Y2and V represents CH, X represents CH or CRaand each of U and W represents N, or each of the Y1, Y2and X represents CH, W represents CH and each of U and V represents N, or each of the Y1, Y2U and V represents CH and each of W and X represents N, or each of the Y1, Y2U and V represents CH, X represents CH or CRaand W represents N, or each of the Y1, Y2, U, W represents CH, X represents CH or CRaand V represents N, or each of the Y1, Y2, V, and W represents CH, X represents CH or CRaand U represents N,
Rais a halogen;
And represents CH2CH(OH), CH2CH(NH2), CH(OH)CH(NH2) or CH(NH2)CH2In represents CH2CH2CH2NH or CONH and D is CH2or
And represents the CH(OH)CH2and represents CH2NH, N(R2)CO or CONH, and D represents CH2or represents-N(R2a)CH2and D is CH(OH), or
And represents the CH(OH)CH(OH), is a CH2NH or CONH and D is CH2or
And represents CH2CH2and represents the FDS is th CH 2CH2CH2NR3, NHCO, CONR4CH2O the PINES2or CH2CH2NH, and D represents CH2or represents CH2NH, and D is a WITH, or a represents a CH2CH2In represents NR4bCH2and D is CH(OH), or
And represents CH=CH, A represents CH2NR5or CONR6and D represents CH2or
But is C≡C, represents a CH2NH and D represents CO or
And is a COCH2In represents CONH and D is CH2or
And represents CH2N(R7), and represents CH2CH2and D represents CH2or represents CH2CH(OH), D represents CH(OH), or
But is NHCH2and represents CH2NH, and D represents CH2or represents CH2NH, and D represents CO or
And represents NHCO, represents CH(R8)NH or CH2CH2and D represents CH2or
And represents OCH2In represents CH=CH or CONH and D is CH2;
R2is a (C1-C4)alkyl;
R2arepresents hydrogen;
R3the submitted is a hydrogen, CO-(CH2)p-COOR3', (CH2)p-COOR3', (C2-C5)acyl or amino(C1-C4)alkyl, or R3is also a (C1-C4)alkyl, which may be one or two times substituted by a hydroxy-group, p denotes an integer from 1 to 4, and R3'represents hydrogen or (C1-C4)alkyl;
R4represents hydrogen or (C1-C4)alkyl;
R4brepresents hydrogen;
R5represents hydrogen or (C2-C5)acyl;
R6represents hydrogen or (C1-C4)alkyl;
R7represents hydrogen or (C1-C4)alkyl, which may be one or two times substituted by groups independently selected from hydroxy-group and amino group;
R8represents hydrogen or (C1-C4)alkyl;
E represents one of the following groups

where Q represents O or S, or
E represents a phenyl group which is once or twice substituted in the meta and/or para-position substituents, each of which is independently selected from the group comprising halogen, (C1-C3)alkyl and trifluoromethyl;
or pharmaceutically acceptable salt of such compounds.

3. The compound of formula I is about to claim 1, which is such that when a represents CH2N(R7), then represents CH2CH2, and D represents CH2or represents CH2CH(OH), D represents CH(OH), R7represents hydrogen or (C1-C4)alkyl which may be substituted once or twice by hydroxy-group;
or pharmaceutically acceptable salt of such compounds.

4. The compound of formula I according to claim 1 or claim 2, in which
R1represents hydrogen or a methoxy group;
each of the Y1, Y2and V represents CH, X represents CH or CF, and each of U and W represents N, or each of the Y1, Y2and X represents CH, W represents CH, and each of U and V represents N, or each of the Y1, Y2U and V represents CH, X represents CH or CF, and W represents N, or each of the Y1, Y2, U, W represents CH, X represents CH or CF, a, V represents N, or each of the Y1, Y2, V, and W represents CH, X represents CH or CF, a U represents N,
And represents the CH(OH)CH2In represents the N(R2)CO and D represents CH2, R3denotes hydrogen or methyl, or a represents a CH2CH2In represents CH2H 2CH2NR3or NHCO, and D represents CH2or Rather it represents a CH2CH2In represents NHCH2and D is CH(OH), R3denotes hydrogen or (C1-C4)alkyl, which may be one or two times substituted by a hydroxy-group, or
And represents CH=CH, A represents CH2NH or CONR6and D represents CH2, R6denotes hydrogen or methyl, or a represents a CH2N(R7), Is a CH2CH2and D represents CH2, R7represents hydrogen or (C1-C4)alkyl, which may be one or two times substituted by a hydroxy-group, or
But is NHCH2In represents CH2NH and D represents CH2or
And represents NHCO, represents CH2NH or CH2CH2and D represents CH2;
E represents one of the groups shown below

where Q represents O or S;
or pharmaceutically acceptable salt of such compounds.

5. The compound of formula I according to claim 1 or claim 2, in which
R1represents hydrogen or a methoxy group;
each of the Y1, Y2and V represents CH, X represents CH or CF, is each of U and W represents N, or each of the Y1, Y2U and V represents CH, X represents CH or CF, and W represents N, or each of the Y1, Y2, U, W represents CH, X represents CH or CF, and V represents N, or each of the Y1, Y2, V, and W represents CH, X represents CH or CF, and U represents N;
And represents CH2CH2In represents CH2NR3and D represents CH2, R3represents hydrogen or (C1-C4)alkyl, which may be one or two times substituted by a hydroxy-group, or
And represents CH=CH, A represents CONH and D is CH2or
And represents CH2N(R7), Is a CH2CH2and D represents CH2, R7represents hydrogen or (C1-C4)alkyl, which may be one or two times substituted by a hydroxy-group, or
But is NHCH2In represents CH2NH and D represents CH2;
E represents a group

where Q represents O or S;
or pharmaceutically acceptable salt of such compounds.

6. The compound of formula I according to claim 1, which is a compound of formula IP1
,
where R1/sup> represents a halogen, a methoxy group or a cyano;
one or two of U, V, W and X are N, and each of the remaining represents CH, or in the case of X, may also represent a CRa;
Rais a halogen;
each of the Y1and Y2represents CH,
And represents CH2CH(OH), CH2CH(NH2), CH(OH)CH(NH2) or CH(NH2)CH2In represents CH2CH2CH2NH or CONH and D is CH2or
And represents the CH(OH)CH2In represents CH2NH, N(R2)CO or CONH and D is CH2or
And represents the CH(OH)CH(OH), is a CH2NH or CONH and D is CH2or
And represents CH2CH2and represents CH2NR3, NHCO or CONR4and D represents CH2or represents CH2NH, and D represents CO or
And represents CH=CH, A represents CH2NR5or CONR6and D represents CH2or
But a With a≡C, b represents CH2NH and D represents CO or
And is a COCH2In represents CONH and D is CH2or
And represents CH2N(R7), Is a CH2CH2/sub> and D represents CH2or
But is NHCH2and represents CH2NH, and D represents CH2or represents CH2NH, and D represents CO or
And represents NHCO, represents CH(R8)NH or CH2CH2and D represents CH2;
R2is a (C1-C4)alkyl;
R3represents hydrogen, (C1-C4)alkyl, CO-(CH2)p-COOH, (C2-C5)acyl or amino(C1-C4)alkyl,
p denotes an integer from 1 to 4;
R4represents hydrogen or (C1-C4)alkyl;
R5represents hydrogen or (C2-C5)acyl;
R6represents hydrogen or (C1-C4)alkyl;
R7represents hydrogen or alkyl;
R8represents hydrogen or alkyl;
E represents a group of the formula

where R is a ring selected from the group comprising the following rings:
,
where Q represents O or S, or
E represents a phenyl group which is once or twice substituted in the meta and/or para-position substituents, each of which is independently selected from the group comprising ha of oven, (C1-C3)alkyl and trifluoromethyl;
or pharmaceutically acceptable salt of such compounds.

7. The compound of formula I according to claim 1, in which R1represents a methoxy group; or a pharmaceutically acceptable salt of such compounds.

8. The compound of formula I according to claim 1, in which E represents one of the following groups:
,
where Z represents CH or N, and Q represents O or S;
or pharmaceutically acceptable salt of such compounds.

9. The connection of claim 8, in which E represents a 2,3-dihydrobenzo[1,4]-dioxin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl or 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl; or a pharmaceutically acceptable salt of such compounds.

10. The compound of formula I according to claim 1, in which E represents a phenyl group which is once or twice substituted in the meta and/or para-position substituents, each of which is independently selected from the group comprising halogen, (C1-C3)alkyl and trifluoromethyl; or a pharmaceutically acceptable salt of such compounds.

11. The compound of formula I according to claim 1, which is selected from the following compounds:
- (E)-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)acrylamide;
- (E)-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-d the hydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]acrylamide;
- (E)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-(3-methoxyaniline-5-yl)acrylamide;
- (E)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-(3-methoxyaniline-5-yl)acrylamide;
- (E)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-N-ethyl-3-(6-methoxy[1,5]naphthiridine-4-yl)acrylamide;
- (E)-3-(3-methoxyaniline-5-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]acrylamide;
- (E)-3-(3-methoxyaniline-5-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]acrylamide;
- (E)-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methyl-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]acrylamide;
- (E)-N-[(R)-3-(3-fluoro-4-were)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)acrylamide;
- (E)-N-[(R)-3-(3-fluoro-4-were)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methylacrylamide;
- (E)-N-[(R)-3-(4-ethylphenyl)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methylacrylamide;
- (E)-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methyl-N-[(R)-2-oxo-3-(4-propylphenyl)oxazolidin-5-ylmethyl]acrylamide;
- (E)-3-(2-cyanohydrin-8-yl)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]acrylamide;
- (E)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-(6-ftorhinolon-4-yl)acrylamide;
- (E)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxy the-6-yl)-2-oxoacridine-5-ylmethyl]-3-(2-methoxyquinoline-8-yl)acrylamide;
- (E)-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methyl-N-[(R)-3-(4-methyl-3-triptoreline)-2-oxoacridine-5-ylmethyl]acrylamide;
- (E)-N-[(R)-3-(3-bromo-4-were)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methylacrylamide;
- (E)-N-[(R)-3-(4-bromo-3-were)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methylacrylamide;
- (E)-N-[(R)-3-(4-bromo-3-forfinal)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-methylacrylamide;
- (E)-N-[(S)-3-(4-ethylphenyl)-2-oxoacridine-5-ylmethyl]-3-(3-methoxyaniline-5-yl)-N-methylacrylamide;
- N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-(6-methoxy[1,5]naphthiridine-4-yl)propionamide;
- 3-(3-methoxyaniline-5-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]propionamide;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(E)-3-(6-methoxy[1,5]naphthiridine-4-yl)allylamino]methyl}oxazolidin-2-he;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[3-(6-methoxy-[1,5]naphthiridine-4-yl)propylamino]methyl}oxazolidin-2-he;
- N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-N-[(E)-3-(6-methoxy[1,5]naphthiridine-4-yl)allyl]ndimethylacetamide;
- 6-((R)-5-{[(E)-3-(6-methoxy[1,5]naphthiridine-4-yl)allylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 6-((R)-5-{[3-(6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 6-((R)-5-{[3-(3-methoxyaniline-5-yl)propyl) - Rev. Mino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-N-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]ndimethylacetamide;
- N-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]succineidae acid;
- N-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]propionamide;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-({ethyl[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}methyl)oxazolidin-2-he;
- (R)-5-({(2-amino-ethyl)[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}methyl)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)oxazolidin-2-he;
- 6-[(R)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
- (R)-3-(3-fluoro-4-were)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)oxazolidin-2-he;
- (R)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)-3-(4-methyl-3-triptoreline)oxazolidin-2-he;
- (R)-3-(4-ethylphenyl)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)oxazolidin-2-he;
- (R)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)-3-(4-propylphenyl)oxazolidin-2-he;
- (R)-3-(3-bromo-4-were)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)oxazolidin-2-he;
- (R)-3-(4-bromo-3-were)-5-({[3-(3-methoxyaniline-5-yl)propyl]methylamino}methyl)oxazolidin-2-he;
- (R)-3-(4-bromo-3-forfinal)-5-({[3-(3-methoxyaniline-5-the l)propyl]methylamino}methyl)oxazolidin-2-he;
- [3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
- (2R,3S)-2,3-dihydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]propionamide;
- (2S,3R)-2,3-dihydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]propionamide;
- N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)propionamide;
- (R)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)propionamide;
- (S)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)propionamide;
- (Z)-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)acrylamide;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[3-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}oxazolidin-2-he;
- N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-2-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)propionamide;
- 2-hydroxy-3-(6-methoxy[1,5]naphthiridine-4-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]propionamide;
- 2-amino-N-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-3-(6-m is toxi[1,5]naphthiridine-4-yl)propionamide;
- (5R)-5-{[2-amino-3-(6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)oxazolidin-2-he;
- [3-(6-methoxy[1,5]naphthiridine-4-yl)prop-2-inyl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
- [2-(6-methoxy[1,5]naphthiridine-4-ylamino)ethyl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
- (S)-2-{[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]amino}-N-(6-methoxy[1,5]naphthiridine-4-yl)propionamide;
- 2-{[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]amino}-N-(6-methoxy[1,5]naphthiridine-4-yl)ndimethylacetamide;
- 2-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-yl]-N-2-(6-methoxyquinoline-4-yl)ethyl]ndimethylacetamide;
- N-[(R)-3-(3-fluoro-4-were)-2-oxoacridine-5-ylmethyl]-3-(3-methoxyaniline-5-yl)-N-methylpropionamide;
- 2-[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-yl]-N-[(R)-2-hydroxy-2-(3-methoxyaniline-5-yl)ethyl]-N-methylacetamide;
- 6-((R)-5-{[2-amino-3-(6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- N-(6-methoxy[1,5]naphthiridine-4-yl)-2-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]amino}ndimethylacetamide;
- N-[(R)-2-hydroxy-2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]-N-methyl-2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-yl]ndimethylacetamide;
- (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5[3-(6-methoxy[1,5]naphthiridine-4-yl)propoxymethyl]oxazolidin-2-he;
- N-[2-(6-methoxy[1,5]naphthiridine-4-yl)ethyl]-2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-yl]ndimethylacetamide;
- 6-((S)-5-{(S)-1-hydroxy-2-[2-(6-methoxy[1,5]naphthiridine-4-yl)ethylamino]ethyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{(S)-1-hydroxy-2-[2-hydroxy-2-(3-methoxyaniline-5-yl)ethylamino]ethyl}oxazolidin-2-he;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[(E)-4-(6-methoxyquinoline-4-yloxy)but-2-enyl]oxazolidin-2-he;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[4-(6-methoxy[1,5]naphthiridine-4-yl)butylamino]methyl}oxazolidin-2-he;
- 6-((R)-5-{[4-(6-methoxy[1,5]naphthiridine-4-yl)butylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[5-(6-methoxy[1,5]naphthiridine-4-yl)pentyl]oxazolidin-2-he;
- 6-{(R)-5-[5-(6-methoxy[1,5]naphthiridine-4-yl)pentyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
- 6-((R)-5-{[3-(6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 6-((R)-5-{[3-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 6-((R)-5-{[3-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[3-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)propylamino]methyl}oxazolidin-2-he;
- (R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-({((S)-2,3-dihydroxy who ropyl)-[3-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}methyl)oxazolidin-2-he;
- 6-[(R)-5-({((S)-2,3-dihydroxypropyl)-[3-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
- 6-[(R)-5-({((R)-2,3-dihydroxypropyl)-[3-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]oxazin-3-one;
- 6-[(R)-5-({((R)-2,3-dihydroxypropyl)-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]oxazin-3-one;
tert - butyl ester {[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}acetic acid;
methyl ether 3-{[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}propionic acid;
- ethyl ester 4-{[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}butyric acid;
- {[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}acetic acid;
- 3-{[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]-[3-(6-methoxy[1,5]naphthiridine-4-yl)propyl]amino}propionic acid;
- 6-((R)-5-{3-[(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 6-((R)-5-{3-[((S)-2,3-dihydroxypropyl)-(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo is[1,4]oxazin-3-one;
- 6-((R)-5-{3-[((R)-2,3-dihydroxypropyl)-(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 6-((R)-5-{3-[(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)-(2-hydroxyethyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{(1R,2S)-1,2-dihydroxy-3-[(6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}oxazolidin-2-he;
- (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{(1R,2S)-3-[(3-fluoro-6-methoxyquinoline-4-ylmethyl)amino]-1,2-dihydroxypropyl}oxazolidin-2-he;
- (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{(1R,2S)-1,2-dihydroxy-3-[(3-methoxyaniline-5-ylmethyl)amino]propyl}oxazolidin-2-he;
- 6-((S)-5-{(1R,2S)-1,2-dihydroxy-3-[(6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 6-((S)-5-{(1R,2S)-3-[(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]-1,2-dihydroxypropyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 6-((S)-5-{(1R,2S)-3-[(3-fluoro-6-methoxyquinoline-4-ylmethyl)amino]-1,2-dihydroxypropyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{(1S,2R)-1,2-dihydroxy-3-[(6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}oxazolidin-2-he;
- 6-((S)-5-{(1S,2R)-3-[(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]-1,2-dihydroxypropyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 6-((S)-5-{(1S,2R)-3-[(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]-1,2-dihydroxypropyl the}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 2-(6-methoxy[1,5]naphthiridine-4-yloxy)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]ndimethylacetamide;
- 6-((R)-5-{[2-(6-methoxy[1,5]naphthiridine-4-ylamino)ethylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
- 6-((R)-5-{[2-(6-methoxy[1,5]naphthiridine-4-ylamino)ethylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 6-((R)-5-{[3-(6-methoxy[1,5]naphthiridine-4-ylamino)propylamino]methyl}-2-oxoacridine-3-yl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
- 6-((R)-5-{3-[(3-aminopropyl)-(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
- 6-((R)-5-{3-[(3-fluoro-6-methoxy[1,5]naphthiridine-4-ylmethyl)-(3-hydroxypropyl)amino]propyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
or pharmaceutically acceptable salt of such compounds.

12. The compound of formula I according to one of claims 1 to 11, or its pharmaceutically acceptable salt as a medicine to prevent or treat bacterial infections.

13. Pharmaceutical composition for preventing or treating a bacterial infection where the specified pharmaceutical composition comprises as an active ingredient a compound of the formula I according to one of claims 1 to 11, or its pharmaceutically acceptable salt and at least one therapeutically inert excipient.

14. The use of the compounds of formula I according to one of claims 1 to 11 or f is matemticas acceptable salts for receiving medicines to prevent or treat bacterial infections.

15. The compound of formula I according to one of claims 1 to 11, or its pharmaceutically acceptable salt for use to prevent or treat bacterial infections.



 

Same patents:

Antiviral compounds // 2505540

FIELD: biotechnologies.

SUBSTANCE: invention pertains to new compounds that have the properties of HCV virus replication inhibitor. In expression I: , A1 is C6aryl, substituted by -X1-R7; X1 is -S-; R7 is C6aryl, not necessarily substituted by one RA; Z1 is -N(RB)-; each of W1 and W2 is N; R1 is hydrogen; R3 and R4 together with carbon atoms, to which they are connected, form 6-member heterocyclic ring containing N as heteroatom, where 6-member heterocyclic ring is not necessary substituted by one RA; A2 represents C6aryl or 5-member heterocyclyl containing N as heteroatom; R2 represents -N(Rb)C(O)C(R5R6)N(R8)-T-Rd, or -LK-B; R6 and R8 together with atoms, to which they are connected, form 5-member heterocyclic ring; the values of radicals RA, R5, T, RC, RD, RD' and RD", LK, B are given in the invention's expression. Invention also pertains to pharmaceutical composition containing the said compounds, method for inhibiting HCV virus replication, method for HCV infection curing and method for obtaining the said compounds.

EFFECT: improving compound application efficiency.

25 cl, 6 tbl, 18 ex

Antiviral compounds // 2505539

FIELD: chemistry.

SUBSTANCE: in formula III:

,

each of X1 and X2 is independently selected from a bond, -CH2-, -O- or -S- and at least one of X1 and X2 is selected from -CH2-, -O- or -S-; each of R7 and R8 is independently selected from hydrogen or C6aryl, optionally substituted with one or more Ra and at least one of R7 and R8 is selected from C6aryl, optionally substituted with one or more Ra; each of Z1 and Z2 is selected from -N(RB)-, each of W1, W2, W3, W4, W5, W6, W7 and W8 is independently selected from N or C(Rd), where Rd in each case is selected from hydrogen; each of R1, R2, R9, R11, R12, R14, R15 and R16 in each case is independently selected from hydrogen or Ra; each of m and n is 0; Ra in each case is independently selected from halogen, hydroxy group, amino group, -LA and -Ls-Re; La in each case is selected from C1-C6-alkyl; values of radicals T, Rb, Rb', Re are given in the claim. The invention also relates to a pharmaceutical composition containing said compounds, a method of inhibiting HCV replication, a method of treating HCV infection and a method of producing said compounds.

EFFECT: high efficiency of using compounds.

7 cl, 6 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1) or a salt thereof, where D1 is a single bond, -N(R11)- or -O-, where R11 is a hydrogen atom or C1-C3 alkyl; A1 is C2-C4 alkylene, or any of divalent groups selected from the following formulae , and ,

where n1 equals 0 or 1; n2 equals 2 or 3; n3 equals 1 or 2; R12 and R13 are each independently a hydrogen atom or C1 -C3 alkyl; v is a bond with D1; and w is a bond with D2; D2 is a single bond, C1-C3 alkylene, -C(O)-, S(O)2-, -C(O)-N(R15)-, or -E-C(O)-, where E is C1-C3 alkylene, and R15 is a hydrogen atom; R1 is a hydrogen atom, C1-C6 alkyl, a saturated heterocyclic group which can be substituted with C1-C6 alkyl groups, an aromatic hydrocarbon ring which can be substituted with C1-C3 alkyl groups, C1-C4 alkoxy groups, halogen atoms, cyano groups, a monocyclic aromatic heterocyclic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, or the following formula ,

where n1 equals 0, 1 or 2; m2 equals 1 or 2; D12 is a single bond, -C(O)- or -S(O)2-; R18 and R19 denote a hydrogen atom; R17 is a hydrogen atom or C1-C3 alkyl; and x is a bond with D2; under the condition that when R17 denotes a hydrogen atom, D12 denotes a single bond; under the condition that when D1 denotes a single bond, A1 denotes a divalent group of said formula (1a-5) or (1a-6); when D1 denotes -N(R11)-, -O-, or -S(O)2-, A1 denotes a single bond, C2-C4 alkylene, or any of divalent groups selected from formulae (1a-1)-(1a-3), where, when A1 denotes a single bond, D2 denotes -E-C(O)-; and D3 is a single bond, -N(R21)-, -N(R21)-C(O) - or -S-, where R21 is a hydrogen atom; and R2 denotes a group of formula ,

where Q denotes an aromatic hydrocarbon ring, a monocyclic aromatic heterocyclic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, a condensed polycyclic aromatic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, or a partially unsaturated monocyclic or a condensed bicyclic carbon ring and a heterocyclic ring; and y denotes a bond with D3; and R23, R24 and R25 each independently denotes a hydrogen atom, a halogen atom, a cyano group, C1-C3 alkyl, which can be substituted with hydroxyl groups, halogen atoms or cyano groups, C1-C4 alkoxy group, which can be substituted with halogen atoms, alkylamino group, dialkylamino group, acylamino group, or the formula ,

where D21 denotes a single bond or C1-C3 alkylene; D22 denotes a single bond or -C(O)-; R26 and R27 each independently denotes a hydrogen atom or C1-C3 alkyl; and z denotes a bond with Q; under the condition that when D22 denotes a single bond, R27 is a hydrogen atom. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula , a IKKβ inhibitor, a method of inhibiting IKKβ, a method of preventing and/or treating an NF-kB-associated or IKKβ-associated disease, and intermediate compounds of formulae and .

EFFECT: obtaining novel isoquinoline derivatives, having useful biological properties.

46 cl, 3 dwg, 38 tbl, 89 ex

FIELD: chemistry.

SUBSTANCE: invention relates to use of novel pyrrolopyrazine derivatives of formula , where variables Q and R are as defined in the claim, which inhibit JAK and SYK.

EFFECT: high effectiveness when treating autoimmune and inflammatory diseases.

11 cl, 59 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to 7-benzoyl-8-hydroxy-6-phenyl-9-(3-phenyl-2-quinoxalinyl)-10H-pyrido[1,2-a]quinoxalin-10-one of formula (1)

EFFECT: obtaining a novel compound which can be used in medicine as a drug having analgesic activity.

3 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to novel imidazopyridine or imidazopyrimidine derivatives of formula (I) and to pharmaceutically acceptable salts and esters thereof, where A is N or C(R6); R1 is hydrogen, lower alkyl; R2 is halogen, C(O)NR7R8 or C(O)OR9; R3 is hydrogen, NR10R11; R4 is hydrogen, lower alkyl; R5 is phenyl or thiazolyl or pyridine, which can be substituted with one substitute independently selected from a group consisting of halogen; R6 is hydrogen, halogen, CN, C3-C6cycloalkyl; R7 and R8 are independently selected from a group consisting of hydrogen, lower alkyl, lower alkoxy-lower alkyl, fluoro-lower alkyl, C3-C6cycloalkyl, N(H,lower alkyl)-lower alkyl, hydroxy- lower alkyl, hydroxy-lower alkoxy- lower alkyl, N(lower alkyl2)C(O)- lower alkyl, lower alkoxy, hydroxy-lower alkyl-oxetanyl- lower alkyl, oxo-tetrahydrofuranyl, tetrahydrofuranyl-lower alkyl, hydroxy-fluoro-lower alkyl, tetrahydrofuranyl, phenyl and thiazolyl or pyridine, or R7 and R8 together with a nitrogen atom with which they are bonded form a heterocyclyl selected from a group consisting of pyrrolidinyl, azetidinyl, morpholinyl, 5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazinyl, 3,4-dihydro- 1H-pyrrolo[1,2-a]pyrazinyl, 2-oxa-6-aza-spiro[3.3]heptyl, 5,6-dihydro- 8H-imidazo[1,2-a]pyrazinyl, [1,4]oxazepanyl, piperazinyl, thiomorpholinyl and 2-oxa-5-aza-bicyclo[2.2.1]heptyl, where the heterocyclyl is optionally substituted with 1 or 2 substitutes independently selected from a group consisting of halogen, lower alkyl, lower alkyl-C(O), lower alkoxy-lower alkyl, oxo, hydroxy, hydroxy-lower alkyl, N(lower alkyl2); R9 is lower alkyl; R10 and R11 together with a nitrogen atom with which they are bonded form a heterocyclyl selected from a group consisting of piperidinyl, morpholinyl. The invention also relates to a pharmaceutical composition based on the compound of formula (I), a method of treating said pathological conditions and use of the compound of formula (I).

EFFECT: obtaining novel imidazopyridine or imidazopyrimidine derivatives which are PDE10A inhibitors.

24 cl, 94 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to pyrazolo[3,4-b]pyridine compounds and a method for production thereof. Described are 2-(6-aryl-4-aroyl-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridin-5-yl)-2-oxo-N-arylacetamides of formula ,

where Ar1=Ph, C6H4Me-4; Ar2=Ph, C6H4Me-4, C6H4Br-4, and a method for production thereof by boiling 1-aryl-4,5-diaroyl-1H-pyrrole-2,3-diones with 5-amino-3-methyl-1-phenyl-1H-pyrazole in a medium of inert aprotic solvent.

EFFECT: obtaining novel compounds which can be used as primary products for synthesis of novel heterocyclic systems and in pharmacology as potential medicinal agents with analgesic activity.

4 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where "----" denotes a bond or is absent; R1 is a C1-4alkoxy group or halogen; R1b is H or C1-3alkyl; U and V each independently denote CH or N; W is CH or N, or, if "----" is absent, W is CH2 or NH; under the condition that at least one of U, V and W is CH or CH2; A is -CH2-CH(R2)-B-NH-* or -CH(R3)-CH2-N(R4)-[CH2]m-*; where asterisks indicate a bond which binds said fragments through a CH2-group with an oxazolidinone fragment; B is CH2 or CO; and R2 is hydrogen, OH or NH2; R3 and R4 both denote hydrogen, or R3 and R4 together form a methylene bridge; m equals 0, 1 or 2; and G is a phenyl which is monosubstituted in position 3 or 4, or disubstituted in positions 3 and 4, where each substitute is independently selected from a group comprising C1-4alkyl, C1-3alkoxy group and halogen; or G is a group selected from groups G1 and G5 where M is CH or N; Q' is S or O; Z1 is N, Z2 is CH and Z3 is CH; or Z1 is CH, Z2 is N and Z3 is CH or N; or Z1 is CH, Z2 is CR5 and Z3 is CH; or Z1 is CH, Z2 is CH and Z3 is N; and R5 is hydrogen or fluorine; or a pharmaceutically acceptable salt thereof. The compound of formula (I) or a pharmaceutically acceptable salt thereof are used as a medicinal agent for preventing or treating bacterial infections.

EFFECT: oxazolidinone derivatives used as antimicrobial agents.

15 cl, 2 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted 4-aminocyclohexane derivatives of general formula I: where: R1 and R2 independently denote C1-3-alkyl, H or R1 and R2 together with an N tom form a (CH2)3, (CH2)4 ring; R3 optionally denotes a phenyl or thienyl linked through a C1-3-alkyl chain, each unsubstituted; or an unsubstituted C1-6-alkyl; R4 denotes indole, pyrrolo[2,3-b]pyridine, pyrrolo[2,3-c]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[3,2-b]pyridine, optionally mono- or multi-substituted with a substitute selected from a group comprising F, CI, Br, CN, CH3, C2H5,' NH2, tert-butyl, Si(ethyl)3, Si(methyl)2(tert-butyl), SO2CH3, SO2-phenyl, C(O)CH3, NO2, SH, CF3, OCF3, OH, OCH3, OC2H5, N(CH3)2; in form of a racemate; enantiomers, diastereomers, mixtures of enantiomers or diastereomers or separately an enantiomer or diastereomers; bases and/or salts of physiologically compatible acids or cations; as well as a drug based on compounds I for treating neuropathic pain.

EFFECT: improved properties.

14 cl, 73 ex

FIELD: chemistry.

SUBSTANCE: invention relates to imidazopyridines of formula I and to a pharmaceutically acceptable salt thereof, where Z1 is CR1; R1 is H; R1' is H; Z2 is CR2; Z3 is CR3; R2 and R3 are H; R4 is H; Y is W-C(O)-; W is or ; R5 is H; X1 is selected from R11' and -OR11'; R11 is independently H or C1-C6 alkyl, optionally substituted -(CR19R20)nCOR16; X4 is ; R6 is halogen, carbocyclyl or -(CR19R20)n-SR16, wherein said carbocyclyl is cyclopropyl or cyclobutyl; R6' is halogen; p equals 1, 2; n equals 0, 1; each R16 is independently H or C1-C6 alkyl; R19 and R20 are independently selected from H or C1-C6 alkyl. The invention also relates to a pharmaceutical composition based on the compound of formula I and a method of inhibiting anomalous cell growth or treating a hyperproliferative disorder, based on use of the compound of formula I.

EFFECT: obtaining novel imidazopyridine derivatives of formula I, which are useful in treating hyperproliferative disorders.

7 cl, 14 ex

FIELD: chemistry.

SUBSTANCE: described are 1,2-disubstituted heterocyclic compounds of formula (I) where HET, X, Y and Z values are presented in description, which are phosphodiesterase 10 inhibitors. Also described are pharmaceutical composition and methods of treating central nervous system (CNS) disorders and other disorders, which can influence CNS function.

EFFECT: among disorders that can be subjected to treatment, there are neurological, neurodegenerative and psychiatric disorders, which include, but are not limited by them, disorders, associated with impairment of cognitive ability or schizophrenic symptoms.

14 cl, 824 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1) or a salt thereof, where D1 is a single bond, -N(R11)- or -O-, where R11 is a hydrogen atom or C1-C3 alkyl; A1 is C2-C4 alkylene, or any of divalent groups selected from the following formulae , and ,

where n1 equals 0 or 1; n2 equals 2 or 3; n3 equals 1 or 2; R12 and R13 are each independently a hydrogen atom or C1 -C3 alkyl; v is a bond with D1; and w is a bond with D2; D2 is a single bond, C1-C3 alkylene, -C(O)-, S(O)2-, -C(O)-N(R15)-, or -E-C(O)-, where E is C1-C3 alkylene, and R15 is a hydrogen atom; R1 is a hydrogen atom, C1-C6 alkyl, a saturated heterocyclic group which can be substituted with C1-C6 alkyl groups, an aromatic hydrocarbon ring which can be substituted with C1-C3 alkyl groups, C1-C4 alkoxy groups, halogen atoms, cyano groups, a monocyclic aromatic heterocyclic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, or the following formula ,

where n1 equals 0, 1 or 2; m2 equals 1 or 2; D12 is a single bond, -C(O)- or -S(O)2-; R18 and R19 denote a hydrogen atom; R17 is a hydrogen atom or C1-C3 alkyl; and x is a bond with D2; under the condition that when R17 denotes a hydrogen atom, D12 denotes a single bond; under the condition that when D1 denotes a single bond, A1 denotes a divalent group of said formula (1a-5) or (1a-6); when D1 denotes -N(R11)-, -O-, or -S(O)2-, A1 denotes a single bond, C2-C4 alkylene, or any of divalent groups selected from formulae (1a-1)-(1a-3), where, when A1 denotes a single bond, D2 denotes -E-C(O)-; and D3 is a single bond, -N(R21)-, -N(R21)-C(O) - or -S-, where R21 is a hydrogen atom; and R2 denotes a group of formula ,

where Q denotes an aromatic hydrocarbon ring, a monocyclic aromatic heterocyclic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, a condensed polycyclic aromatic ring containing one or two heteroatoms selected from a group consisting of a nitrogen atom, a sulphur atom and an oxygen atom, or a partially unsaturated monocyclic or a condensed bicyclic carbon ring and a heterocyclic ring; and y denotes a bond with D3; and R23, R24 and R25 each independently denotes a hydrogen atom, a halogen atom, a cyano group, C1-C3 alkyl, which can be substituted with hydroxyl groups, halogen atoms or cyano groups, C1-C4 alkoxy group, which can be substituted with halogen atoms, alkylamino group, dialkylamino group, acylamino group, or the formula ,

where D21 denotes a single bond or C1-C3 alkylene; D22 denotes a single bond or -C(O)-; R26 and R27 each independently denotes a hydrogen atom or C1-C3 alkyl; and z denotes a bond with Q; under the condition that when D22 denotes a single bond, R27 is a hydrogen atom. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula , a IKKβ inhibitor, a method of inhibiting IKKβ, a method of preventing and/or treating an NF-kB-associated or IKKβ-associated disease, and intermediate compounds of formulae and .

EFFECT: obtaining novel isoquinoline derivatives, having useful biological properties.

46 cl, 3 dwg, 38 tbl, 89 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) where "----" denotes a bond or is absent; R1 is a C1-4alkoxy group or halogen; R1b is H or C1-3alkyl; U and V each independently denote CH or N; W is CH or N, or, if "----" is absent, W is CH2 or NH; under the condition that at least one of U, V and W is CH or CH2; A is -CH2-CH(R2)-B-NH-* or -CH(R3)-CH2-N(R4)-[CH2]m-*; where asterisks indicate a bond which binds said fragments through a CH2-group with an oxazolidinone fragment; B is CH2 or CO; and R2 is hydrogen, OH or NH2; R3 and R4 both denote hydrogen, or R3 and R4 together form a methylene bridge; m equals 0, 1 or 2; and G is a phenyl which is monosubstituted in position 3 or 4, or disubstituted in positions 3 and 4, where each substitute is independently selected from a group comprising C1-4alkyl, C1-3alkoxy group and halogen; or G is a group selected from groups G1 and G5 where M is CH or N; Q' is S or O; Z1 is N, Z2 is CH and Z3 is CH; or Z1 is CH, Z2 is N and Z3 is CH or N; or Z1 is CH, Z2 is CR5 and Z3 is CH; or Z1 is CH, Z2 is CH and Z3 is N; and R5 is hydrogen or fluorine; or a pharmaceutically acceptable salt thereof. The compound of formula (I) or a pharmaceutically acceptable salt thereof are used as a medicinal agent for preventing or treating bacterial infections.

EFFECT: oxazolidinone derivatives used as antimicrobial agents.

15 cl, 2 tbl, 44 ex

FIELD: chemistry.

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

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

18 cl, 18 dwg, 10 tbl, 19 ex

FIELD: chemistry.

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

,

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

EFFECT: improved properties of compounds.

6 cl, 2 tbl, 42 ex

FIELD: medicine, pharmaceutics.

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

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

7 cl, 1 tbl, 61 ex

FIELD: medicine, pharmaceutics.

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

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

8 cl, 1047 ex, 78 tbl

FIELD: medicine, pharmaceutics.

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

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

67 cl, 1 tbl, 4393 ex

FIELD: medicine, pharmaceutics.

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

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

2 cl, 2 dwg, 2 tbl, 13 ex

FIELD: chemistry.

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

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

12 cl, 7 tbl, 36 ex

FIELD: chemistry.

SUBSTANCE: described are 1,2-disubstituted heterocyclic compounds of formula (I) where HET, X, Y and Z values are presented in description, which are phosphodiesterase 10 inhibitors. Also described are pharmaceutical composition and methods of treating central nervous system (CNS) disorders and other disorders, which can influence CNS function.

EFFECT: among disorders that can be subjected to treatment, there are neurological, neurodegenerative and psychiatric disorders, which include, but are not limited by them, disorders, associated with impairment of cognitive ability or schizophrenic symptoms.

14 cl, 824 ex

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