Oxazolidine antibiotics

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to derivatives of antibiotics, which represent compounds of formula (I) and their pharmaceutically acceptable salts, where U, V, W, X, R1, R2, R3, R4, R5, R6, A, B, D, E, G, m and n are determined in description. Invention also relates to pharmaceutical composition, containing said compounds and their application for obtaining medication for prevention or treatment of bacterial infections.

EFFECT: obtaining useful antimicrobial agents, efficient against various pathogens of people and animals.

23 cl, 1 tbl, 186 ex

 

The text descriptions are given in facsimile form.

1. The use of the compounds of formula (I)
,
where R1represents hydrogen, alkoxygroup, halogen or cyano;
one or two of U, V, W and X are N, and each of the remaining represents CH, or, in case X represents CRa;
Rarepresents hydrogen or halogen;
R6represents hydrogen or (C1-C4)alkyl;
And is represented by N, A represents N, D represents a bond, E represents CH2or, R2, R3, R4and R5each represent H, m represents 2, n represents 1;
or
And is represented by N, A represents N, D represents a bond, E represents CH2or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, or R4and R5represent H, a R2and R3VM is the wall with the carbon atom, to which they are attached, form a carbonyl group, or R2and R3represent H, a R4and R5together with the carbon atom to which they are attached, form a carbonyl group, or R2and R4represent H, a R3and R5together form a methylene bridge, a m and n each represent 1; or
And is represented by N, is(OH), D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
And is represented by N, A represents CH, D represents NRbE represents CH2, R2, R3, R4and R5each represent H, Rbrepresents H or (C1-C4)alkyl, a m and n each represent 1; or
And is represented by N, A represents CH, D represents NH, E represents CH2, R2, R3, R4and R5each represent H, m represents 2, n represents 0; or
And is(HE)represents N, D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
And is represented by N, A represents CH, D represents NRc, Predstavljaet a CH 2WITH or CH2CH2, R2, R3, R4and R5each represent H, a Rcrepresents H or (C1-C4)alkyl, or Rc, R3, R4and R5each represent H, and R2represents a group selected from a hydroxy-group, (C1-C4)alkoxygroup, (C1-With4)alkoxycarbonyl and carboxypropyl, or R3, R4and R5each represent H, a Rcforms together with R2ethane-1,2-dilny bridge, m represents 1 and n represents 0; or
And is represented by N, A represents CH, D represents *-CH(Rd)-(N(Re)where the asterisk indicates the bond attached to b, E represents CH2or, Rd, R2, R3, R4and R5each represent H, and Rerepresents H or (C1-C4)alkyl, or Re, R3, R4and R5each represent H, a Rdand R2together form a bond, or Rd, R2, R3and R5each represent H, a Reand R4together form a methylene bridge, or Rd, Re, R3, R4and R5each represent H, a R2represents a hydroxy-group, m represents 1 and n represents 0; or
And is represented by N, is the Oh CH, D represents *-CONH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
And is represented by N, A represents CH, D represents NH, E represents CH2or, R2, R3and R5each represent H, a R4represents hydroxymethyl, m represents 0 and n represents 1; or
And is represented by N, is(OH), D represents *-CH2-NH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
And is represented by N, A represents CH, D represents *-CO-NH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 0; or
And is represented by N, A represents CH, D represents *-CH2-N(Rf)where the asterisk indicates the bond attached to b, E represents CH2CH2CH2or, R2, R3, R4and R5each represent H, Rfrepresents H or (C1-C )alkyl, a m and n each represent 0; or
And is represented by N, A represents CH, D represents NRgE represents CH2CH2CH2WITH or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, Rgrepresents H, (C1-C4)alkyl or (C2-C4)alkyl, which is mono - or disubstituted by hydroxy-group; and m and n each represent 0;
G represents phenyl, which is unsubstituted, monosubstituted at position 3 or 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-C4)alkyl, (C1-C4)alkoxygroup, foralkyl, forelcosure, cyano, halogen, and-NRN1RN2; or
G represents pyridin-2-yl, monosubstituted in position 5 where the Deputy is selected from the group comprising (C1-C4)alkyl and foralkyl;
or
G represents 6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl; or
G represents a group selected from the group including:
,,,,
and,
where Rhis salavtore or fluorine;
M represents CH or N, and Q and Q' independently represent O or S; and
RN1and RN2independently represent a (C1-C4)alkyl or together with the nitrogen to which they are bound, form a pyrolidine ring, or pharmaceutically acceptable salts of such compounds for receiving medicines to prevent or treat bacterial infections.

2. The use according to claim 1, the compounds of formula (I) according to claim 1 or its pharmaceutically acceptable salt, where
R6represents hydrogen;
And is represented by N, A represents N, D represents a bond, E represents CH2or, R2, R3, R4and R5each represent H, m represents 2, n represents 1; or a represents N, A represents N, D represents a bond, E represents CH2or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, or R4and R5represent H, a R2and R3together with the carbon atom to which they are attached, form a carbonyl group, or R2and R3represent H, a R4and R5together with the carbon atom to which they are attached, form a carbonyl group, a m and n each represent 1; or
And represents N, In represents C(OH), D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or a represents N, A represents CH, D represents NRbE represents CH2, R2, R3, R4and R5each represent H, Rbrepresents H or (C1-C4)alkyl, a m and n each represent 1; or
And is represented by N, A represents CH, D represents NH, E represents CH2, R2, R3, R4and R5each represent H, m represents 2, n represents 0; or
And is(HE)represents N, D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n represent 1; or
And is represented by N, A represents CH, D represents NRcE represents CH2WITH or CH2CH2; R2, R3, R4and R5each represent H, a Rcrepresents H or (C1-C4)alkyl, or Rc, R3, R4and R5each represent H, a R2represents a group selected from a hydroxy-group, (C1-C4)alkoxygroup, (C1-C4)is alkoxycarbonyl and carboxypropyl, or R3, R4and R5each represent H, a Rcforms together with R2ethane-1,2-dilny bridge, m represents 1 and n represents 0; or
And is represented by N, A represents CH, D represents *-(CH(Rd)-N(Re)where the asterisk indicates the bond attached to b, E represents CH2or, Rd, R2, R3, R4and R5each represent H, a Rerepresents H or (C1-C4)alkyl, or Re, R3, R4and R5each represent H, a Rdand R2together form a bond, or Rd, R2, R3and R5each represent H, a Reand R4together form a methylene bridge, or Rd, Re, R3, R4and R5each represent H, a R2represents a hydroxy-group, m represents 1 and n represents 0; or
And is represented by N, A represents CH, D represents *-CONH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
And is represented by N, A represents CH, D represents NH, E represents CH2or, R2, R3and R5each represent H,a R 4represents hydroxymethyl, m represents 0 and n represents 1; or
And is represented by N, A represents CH, D represents *-CH2-N(Rf)where the asterisk indicates the bond attached to b, E represents CH2CH2CH2or (especially CH2or CO), R2, R3, R4and R5each represent H, Rfrepresents H or (C1-C4)alkyl, a m and n each represent 0; or
And is represented by N, A represents CH, D represents NRgE represents CH2CH2CH2WITH or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, Rgrepresents H, (C1-C4)alkyl or 2-hydroxyethyl, a, m and n each represent 0; and
G represents phenyl, which is unsubstituted, monosubstituted at position 3 or 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-C4)alkyl, (C1-C4)alkoxygroup, foralkyl, forelcosure, cyano, halogen, and-NRN1RN2; or
G represents pyridin-2-yl, monosubstituted in position 5 where the Deputy is selected from the group comprising (C1-C4)al the sludge and foralkyl;
or
G represents 6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl; or
G represents a group selected from the group including:
,,,and
,
where M represents CH or N, and Q and Q' independently represent O or S.

3. The use according to claim 1, the compounds of formula (I) according to claim 1 or its pharmaceutically acceptable salt, where the compound of formula (I) is a compound of formula (IP1)
,
where R1is alkoxygroup, halogen or cyano;
one or two of U, V, W and X are N, and each of the remaining represents CH, or, in case X represents CRa;
Rarepresents hydrogen or halogen;
And is represented by N, A represents N, D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
And is represented by N, is(OH), D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
And is(HE)represents N, D represents a link to the e l e C E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
And is represented by N, A represents CH, D represents *-CH2-NH-, where the asterisk indicates the bond attached to b, E represents CH2or, R2, R3, R4and R5each represent H, a, m and n each represent 0; or
And is represented by N, A represents CH, D represents NH, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0;
G represents phenyl, which is unsubstituted, monosubstituted at position 3 or 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-C4)alkyl, (C1-C4)alkoxygroup, foralkyl, forelcosure, cyano, halogen, and-NRN1RN2; or
G represents pyridin-2-yl, monosubstituted in position 5 where the Deputy is selected from the group comprising (C1-C4)alkyl and foralkyl;
or
G represents a group selected from the group including:
,,and
where Q and Q' independently represent with the battle O or S; and
RN1and RN2independently represent a (C1-C4)alkyl or together with the nitrogen atom to which they are attached, form a pyrolidine ring, or pharmaceutically acceptable salt of such compounds.

4. The use according to claim 1, the compounds of formula (I) according to claim 1 or its pharmaceutically acceptable salt, where the compound of formula (I) is a compound selected from the group including:
(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]amino}methyl)oxazolidin-2-he;
[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]amide(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-hydroxy-4-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-1-ylmethyl]oxazolidin-2-he;
3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-hydroxy-1-(6-methoxyquinazoline-4-yl)piperidine-4-ylmethyl]oxazolidin-2-he;
3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-hydroxy-1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylmethyl]oxazolidin-2-he;
3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-(6-methoxyquinazoline-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
6-{5-[4-(6-methoxyquinazoline-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-(methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(3-trifloromethyl)oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(4-trifloromethyl)oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-phenyloxazolidine-2-he;
(R)-3-(4-bromo-3-forfinal)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3,4-acid)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(4-forfinal)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(3-triptoreline)oxazolidin-2-he;
(R)-3-(3-chloro-4-forfinal)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(4-methyl-3-triptoreline)oxazolidin-2-he;
(R)-3-benzothiazol-6-yl-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(4-deformational)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
3-{(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}benzonitrile;
6-{(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(4-pyrrolidin-1-ylphenyl)oxazolidin-2-he;
(R)-5-[4-(6-IU is hydroxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(3-methoxyphenyl)oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(4-propylphenyl)oxazolidin-2-he;
(R)-3-(4-ethylphenyl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3,4-dimetilfenil)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3-chloro-4-methoxyphenyl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3,4-differenl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(4-fluoro-3-were)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(4-bromo-3-were)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3-bromo-4-were)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(4-methoxy-3-triptoreline)oxazolidin-2-he;
(R)-3-(3-dimethylaminophenyl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-benzo[1,3]dioxol-5-yl-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3-fluoro-4-were)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(S)-3-(3-fluoro-4-were)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
6-{(S)-5-[4-(-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(S)-3-(3-forfinal)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]oxazolidin-2-he;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(5-methylpyridin-2-yl)oxazolidin-2-he;
5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-3-(5-triptorelin-2-yl)oxazolidin-2-he;
6-((R)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
(R)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-3-(3-fluoro-4-were)oxazolidin-2-he;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(6-methoxyquinoline-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
(R)-3-(3-fluoro-4-were)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}oxazolidin-2-he;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]IU the Il}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
6-((R)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(6-methoxyquinazoline-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
6-((R)-5-{[1-(6-methoxyquinazoline-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-[(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
6-((S)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-(5-{2-[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]ethyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-[(S)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-yl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-yl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-yl]amide (S)-3-(3-fluoro-4-were)-2-oxoacridine-5-carboxylic acid;
[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-yl]amide (S)-3-(3-fluoro-4-were)-2-oxoacridine-5-carboxylic acid;
6-((R)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
6-((R)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
(R)-3-(3-fluoro-4-were)-5-{[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
(R)-3-(3-fluoro-4-were)-5-{[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
6-((R)-5-{[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
ethyl ester of (3R*,4S*)-1-(6-methoxy[1,5]naphthiridine-4-yl)-4-{[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]amino}pyrrolidin-3-carboxylic acid;
(3R*,4S*)-1-(6-methoxy[1,5]naphthiridine-4-yl)-4-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]amino}pyrrolidin-3-carboxylic acid;
6-((R)-5-{[(3R*,4R*)-4-methoxy-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]enous the n-3-one;
6-((R)-5-{[(3R*,4R*)-4-hydroxy-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(3R*,4R*)-4-hydroxy-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
[(3R,5S)-5-hydroxymethyl-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-yl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
6-((R)-5-{[(3R,5S)-5-hydroxymethyl-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-[(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
[1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
[1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amide (S)-3-(3-fluoro-4-were)-2-oxoacridine-5-carboxylic acid;
6-[(R)-5-({[4-hydroxy-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
[(R)-3-(3-fluoro-4-were)-2-oxoacridine-5-ylmethyl]amide 1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-carboxylic acid;
[(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-ylmethyl]amide 1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-carboxylic acid;
6-(5-{2-[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)PIR is ridin-3-ylamino]ethyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-(5-{2-[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]ethyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
(R)-3-(3-fluoro-4-were)-5-{[(1a,5A,6a)-3-(6-methoxy[1,5]naphthiridine-4-yl)-3-azabicyclo[3.1.0]Gex-6-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[(1A,5a,6A)-3-(6-methoxy[1,5]naphthiridine-4-yl)-3-azabicyclo[3.1.0]Gex-6-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(3aR*,6aR*)-1-(6-methoxy[1,5]naphthiridine-4-yl)hexahydrofuro[3,4-b]pyrrol-5-yl]methyl}oxazolidin-2-he;
6-{{(R)-5-[(3aR*,6aR*)-1-(6-methoxy[1,5]naphthiridine-4-yl)hexahydrofuro[3,4-b]pyrrol-5-yl]methyl}-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[(3aR*,6aR*)-1-(6-methoxy[1,5]naphthiridine-4-yl)hexahydrofuro[3,4-b]pyrrole-5-carbonyl]oxazolidin-2-he;
6-{(R)-5-{[(3aR*,6aR*)-5-(6-methoxy[1,5]naphthiridine-4-yl)hexahydrofuro[3,4-b]pyrrol-1-yl]methyl}-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[(3aR*,6aR*)-5-(6-methoxy[1,5]naphthiridine-4-yl)hexahydrofuro[3,4-b]pyrrol-1-yl]methyl}oxazolidin-2-he;
(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[(3aR*,6aR*)-5-(6-methoxy[1,5]naphthiridine-4-yl)hexahydrofuro[3,4-b]pyrrole-1-carbonyl]oxazolidin-2-he;
6-{(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]oxazin-3-one;
6-{(R)-5-[4-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacetate--yl}-4H-benzo[1,4]oxazin-3-one;
6-{(R)-5-[4-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-(4-quinoline-4-reparation-1-ylmethyl)oxazolidin-2-he;
[3-(3-fluoro-4-were)-2-oxoacridine-5-ylmethyl]-4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-2-he;
6-{(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)-3-oxopiperidin-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-3-ylamino]methyl}oxazolidin-2-he;
6-{(R)-5-[4-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]oxazin-3-one;
6-{(R)-5-[4-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]oxazin-3-one;
6-{(R)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]oxazolidin-2-he;
(R)-3-(3-fluoro-4-were)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]oxazolidin-2-he;
(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-carbonyl]oxazolidin-2-he;
3-(6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl)-5-[4-(6-methoxy[1,5]naphthiridine-4-reparation-1-ylmethyl]oxazolidin-2-he;
(R)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-({[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-yl]methylamino} methyl)oxazolidin-2-he;
6-{5-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-((R)-5-{2-[4-(6-methoxy[1,5]naphthiridine-4-yl)piperazine-1-yl]-2-oxoethyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
N-[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]-2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-yl]ndimethylacetamide;
[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]amide (S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-2-oxoacridine-5-carboxylic acid;
6-[(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]methylamino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
(S)-3-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]methylamino}methyl)oxazolidin-2-he;
6-((R)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
(R)-3-(3-fluoro-4-were)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamine is]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
6-[(R)-5-({[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-yl]methylamino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[4-hydroxy-4-(6-methoxyquinoline-4-yl)piperidine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[4-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)-4-hydroxypiperidine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-[(R)-5-({[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]oxazin-3-one;
6-[(R)-5-({(2-hydroxyethyl)-[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
6-[(R)-5-({[3-hydroxy-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]amide (S)-3-(3-fluoro-4-were)-2-oxoacridine-5-carboxylic acid;
6-((R)-5-{[1-(6-methoxy-2-methylinosine-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[4-hydroxy-4-(6-methoxyquinoline-4-yl)piperidine-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]oxazin-3-one;
(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)-3-phenyloxazolidine-2-he;
(R)-3-(4-deformational)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)-3-(4-m is Tyl-3-triptoreline)oxazolidin-2-he;
(R)-3-(3-chloro-4-forfinal)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(4-ethylphenyl)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(3,4-dimetilfenil)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)-3-(4-propylphenyl)oxazolidin-2-he;
(R)-3-(3-dimethylaminophenyl)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(4-bromo-3-forfinal)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(3-bromo-4-were)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(4-bromo-3-were)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-benzothiazol-6-yl-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-benzo[1,3]dioxol-5-yl-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-benzothiazol-5-yl-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(3-forfinal)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
[(R)-3-(3-fluoro-4-were)-2-oxoacridine-5-ylmethyl]amide 1-(6-methoxy[1,5]naphthiridine-4-yl)shall seiden-3-carboxylic acid;
3-(3-fluoro-4-were)-5-(2-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]amino}ethyl)oxazolidin-2-he;
6-[(R)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)-2-oxoacridine-3-yl]-4H-pyrido[3,2-b][1,4]oxazin-3-one;
6-{(R)-5-[(1S,4S)-5-(6-methoxy[1,5]naphthiridine-4-yl)-2,5-diazabicyclo[2.2.1]hept-2-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]oxazin-3-one;
6-{(R)-5-[(1S,4S)-5-(6-methoxy[1,5]naphthiridine-4-yl)-2,5-diazabicyclo[2.2.1]hept-2-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
(R)-3-(6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-yl]methylamino}methyl)oxazolidin-2-he;
(R)-3-(3-fluoro-4-were)-5-({[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylmethyl]amino}methyl)oxazolidin-2-he;
7-fluoro-6-((R)-5-{[1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(6-methoxyquinoline-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
6-((R)-5-{[1-(3-methoxyaniline-5-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(2-methoxyquinoline-8-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(7-fluoro-2-methoxyquinoline-8-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{[1-(6-ftorhinolon-4-yl)azetidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-on;
4-(3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]amino}azetidin-1-yl)quinoline-6-carbonitrile;
6-[(R)-5-({[1-(2-methoxyquinoline-8-yl)azetidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
6-[(R)-5-({[1-(3-methoxyaniline-5-yl)azetidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
6-((S)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((S)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-{(S)-5-[4-(6-methoxy[1,5]naphthiridine-4-yl)[1,4]diazepan-1-ylmethyl]-2-oxoacridine-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-[(R)-5-({[(R)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]oxazin-3-one;
6-[(R)-5-({[(S)-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]oxazin-3-one;
(R)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-3-(4-methoxyphenyl)oxazolidin-2-he;
(R)-3-(4-ethoxyphenyl)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
(R)-3-(4-deformational)-5-{[(S)-1-(3-fluoro-6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[(S)-1-(6-methoxyquinoline-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]enous the n-3-one;
6-[(R)-5-({[(S)-1-(6-methoxyquinoline-4-yl)pyrrolidin-3-ylmethyl]amino}methyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one;
(R)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}-3-(4-methoxyphenyl)oxazolidin-2-he;
(R)-3-(4-ethoxyphenyl)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}oxazolidin-2-he;
(R)-3-(4-deformational)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)azetidin-3-ylamino]methyl}oxazolidin-2-he;
6-((R)-5-{[(R)-1-(6-ftorhinolon-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
4-((R)-3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]amino}pyrrolidin-1-yl)quinoline-6-carbonitrile;
6-((R)-5-{[1-(6-ftorhinolon-4-yl)piperidine-4-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]thiazin-3-one;
4-(4-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethyl]amino}piperidine-1-yl)quinoline-6-carbonitrile;
6-((R)-5-{[(3S,4S)-4-methoxy-1-(6-methoxy[1,5]naphthiridine-4-yl)pyrrolidin-3-ylamino]methyl}-2-oxoacridine-3-yl)-4H-benzo[1,4]oxazin-3-one;
(R)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}-3-(4-methoxyphenyl)oxazolidin-2-he;
(R)-3-(4-ethoxyphenyl)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}oxazolidin-2-he;
(R)-3-(4-deformational)-5-{[1-(6-methoxy[1,5]naphthiridine-4-yl)piperidine-4-ylamino]methyl}oxazolidin-2-it; and
6-[(R)-5-({[1-(6-methoxyquinoline-4-yl)azetidin-3-ylmethyl]amino}is ethyl)-2-oxoacridine-3-yl]-4H-benzo[1,4]thiazin-3-one.

5. The compound of formula (IN)
,
where R1represents hydrogen, alkoxygroup, halogen or cyano;
one or two of U, V, W and X are N, and each of the remaining represents CH, or, in case X represents CRa;
Rarepresents hydrogen or halogen;
R6represents hydrogen or (C1-C4)alkyl;
And represents N;
In represents N, D represents a bond, E represents CH2or, R2, R3, R4and R5each represent H, m represents 2, n represents 1; or
In represents N, D represents a bond, E represents CH2or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, or R4and R5represent H, a R2and R3together with the carbon atom to which they are attached, form a carbonyl group, or R2and R3represent H, a R4and R5together with the carbon atom to which they are attached, form a carbonyl group, or R2and R4represent H, a R3and R5together form a methylene bridge, m and n each represent 1; or
In represents C(OH), D, t is possessing a relationship E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
In represents CH, D represents NRbE represents CH2, R2, R3, R4and R5each represent H, Rbrepresents H or (C1-C4)alkyl, a m and n each represent 1; or
In represents CH, D represents NH, E represents CH2, R2, R3, R4and R5each represent H, m represents 2, n represents 0; or
In represents CH; D represents NRc; E is CH2WITH or CH2CH2; R2, R3, R4and R5each represent H, and Rcrepresents H or (C1-C4)alkyl, or Rc, R3, R4and R5each represent H, and R2represents a group selected from a hydroxy-group, (C1-C4)alkoxygroup, (C1-C4)alkoxycarbonyl and carboxypropyl, or R3, R4and R5each represent H, a Rctogether with R2forms ethane-1,2-dilny bridge, m represents 1 and n represents 0; or
In represents CH; D represents *-CH(Rd)-N(Re)where the asterisk indicates the bond attached to b, E PR is dstanley a CH 2or, Rd, R2, R3, R4and R5each represent H, and Rerepresents H or (C1-C4)alkyl, or Re, R3, R4and R5each represent H, a Rdand R2together form a bond, or Rd, R2, R3and R4each represent H, a Reand R4together form a methylene bridge, or Rd, Re, R3, R4and R5each represent H, and R2represents a hydroxy-group, m represents 1 and n represents 0; or
In represents CH, D represents *-CONH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
In represents CH, D represents NH, E represents CH2or, R2, R3and R5each represent H, and R4represents hydroxymethyl, m represents 0 and n represents 1; or
In represents C(OH), D represents *-CH2-NH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
In represents CH, D represents *CO-NH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, a, m and n denotes 0; or
In represents CH, D represents *-CH2-N(Rf)where the asterisk indicates the bond attached to b, E represents CH2CH2CH2or, R2, R3, R4and R5each represent H, Rfrepresents H or (C1-C4)alkyl, a m and n each represent 0; or
In represents CH, D represents NRgE represents CH2CH2CH2WITH or *the PINES;where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, Rgrepresents H, (C1-C4)alkyl or (C2-C4)alkyl, which is mono - or disubstituted by hydroxy-group, a m and n each represent 0;
G represents phenyl, which is unsubstituted, monosubstituted at position 3 or 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-C4)alkyl, (C1-C4)alkoxygroup, foralkyl, forelcosure, cyano, halogen, and-NRN1RN2; or
G represents pyridin-2-yl, monogamists is in position 5, where the Deputy is selected from the group comprising (C1-C4)alkyl and foralkyl;
or
G represents 6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl; or
G represents a group selected from the group including:
,,,,
and,
where Rhrepresents a hydrogen or fluorine;
M represents CH or N, and Q and Q' independently represent O or S; and
RN1and RN2independently represent a (C1-C4)alkyl or together with the nitrogen atom to which they are attached, form a pyrolidine ring,
or pharmaceutically acceptable salt of such compounds.

6. The compound of formula (IN) according to claim 5, where
R6represents hydrogen;
In represents N, D represents a bond, E represents CH2or, R2, R3, R4and R5each represent H, m represents 2, n represents 1; or
In represents N, D represents a bond, E represents CH2or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, or R4and R5represent H, a R2and R 3together with the carbon atom to which they are attached, form a carbonyl group, or R2and R3represent H, a R4and R5together with the carbon atom to which they are attached, form a carbonyl group, m and n each represent 1; or
In represents C(OH), D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
In represents CH, D represents NRbE represents CH2, R2, R3, R4and R5each represent H, Rbrepresents H or (C1-C4)alkyl, a m and n each represent 1; or
In represents CH, D represents NH, E represents CH2, R2, R3, R4and R5each represent H, m represents 2, n represents 0; or
In represents CH, D represents NRcE represents CH2WITH or CH2CH2, R2, R3, R4and R5each represent H, a Rcrepresents H or (C1-C4)alkyl, or Rc, R3, R4and R5each represent H, a R2represents a group selected from a hydroxy-group, (C1-C4)alkoxygroup, (C1-C4/sub> )alkoxycarbonyl and carboxypropyl, or R3, R4and R5each represent H, and Rctogether with R2forms ethane-1,2-dilny bridge, m represents 1 and n represents 0; or
In represents CH, D represents *-CH(Rd)-N(Re)where the asterisk indicates the bond attached to b, E represents CH2or, Rd, R2, R3, R4and R5each represent H, and Rerepresents H or (C1-C4)alkyl, or Re, R3, R4and R5each represent H, a Rdand R2together form a bond, or Rd, R2, R3and R5each represent H, a Reand R4together form a methylene bridge, or Rd, Re, R3, R4and R5each represent H, a R2represents a hydroxy-group, m represents 1 and n represents 0; or
In represents CH, D represents *-CONH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
In represents CH, D represents NH, E represents CH2or, R2, R3and R5each represent H, and R4is a guide oximeter, m represents 0 and n represents 1; or
In represents CH, D represents *-CH2-N(Rf)where the asterisk indicates the bond attached to b, E represents CH2CH2CH2or, R2, R3, R4and R5each represent H, Rfrepresents H or (C1-C4)alkyl, a m and n each represent 0; or
In represents CH, D represents NRgE represents CH2CH2CH2WITH or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, Rgrepresents H, (C1-C4)alkyl or 2-hydroxyethyl, a, m and n each represent 0; and
G represents phenyl, which is unsubstituted, monosubstituted at position 3 or 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-With4)alkyl, (C1-C4)alkoxygroup, foralkyl, forelcosure, cyano, halogen, and-NRN1RN2; or
G represents pyridin-2-yl, monosubstituted in position 5 where the Deputy is selected from the group comprising (C1-C4)alkyl and foralkyl;
or
G represents 6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl; or
G represents a group which, selected from the group including:
,,,and
,
where M represents CH or N, and Q and Q' independently represent O or S,
or pharmaceutically acceptable salt of such compounds.

7. The compound of formula (IN) according to claim 5, which is a compound of formula (IN-P1)

where R1is alkoxygroup, halogen or cyano;
one or two of U, V, W, and X represent N, and each of the remaining represents CH, or, in case X represents CRa;
Rarepresents hydrogen or halogen;
And represents N;
In represents N, D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
In represents C(OH), D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
In represents CH, D represents *-CH2-NH-, where the asterisk indicates the bond attached to b, E represents CH2or, R2, R3, R4and R5each pose is a N, a m and n each represent 0; or
In represents CH, D represents NH, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0;
G represents phenyl, which is unsubstituted, monosubstituted at position 3 or 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-C4)alkyl, (C1-C4)alkoxygroup, foralkyl,
forelcosure, cyano, halogen, and-NRN1RN2; or
G represents pyridin-2-yl, monosubstituted in position 5 where the Deputy is selected from the group comprising (C1-C4)alkyl and foralkyl;
or
G represents a group selected from the group including:
,,and,
where Q and Q' independently represent O or S; and
RN1and RN2independently represent a (C1-C4)alkyl or together with
the nitrogen atom to which they are attached, form a pyrolidine ring, or
pharmaceutically acceptable salt of such compounds.

8. The compound of formula (IN) according to claim 5, where two of U, W and X are N and the remaining and V each represent CH, or, in the case of X, assuming yet a CR awhere Rarepresents hydrogen or fluorine, or a pharmaceutically acceptable salt of such compounds.

9. The compound of formula (IN) according to claim 5, where a represents N, and
In represents N, D represents a bond, E represents CH2or, R2, R3, R4and R5each represent H, m represents 2, and denotes 1; or
In represents N, D represents a bond, E represents CH2or *the PINES2where the asterisk indicates the bond attached to, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
In represents C(OH), D represents a bond, E represents CH2, R2, R3, R4and R5each represent H, a, m and n each represent 1; or
In represents CH, D represents NRbE represents CH2, R2, R3, R4and R5each represent H, Rbrepresents H or (C1-C4)alkyl, a m and n each represent 1; or
In represents CH, D represents NRcE represents CH2WITH or CH2CH2, R2, R3, R4and R5each represent H, a Rcrepresents H or (C1-C4)alkyl, or R3,R 4and R5each represent H, a Rcforms together with R2ethane-1,2-dilny bridge, m represents 1 and n represents 0; or
In represents CH, D represents *-CH(Rd)-N(Re)where the asterisk indicates the bond attached to b, E represents CH2or, Rd, R2, R3, R4and R5each represent H, a Rerepresents H or (C1-C4)alkyl, or Re, R3, R4and R5each represent H, a Rdand R2together form a bond, m is 1, and n denotes 0; or
In represents CH, D represents *-CONH-, where the asterisk indicates the bond attached to b, E represents CH2, R2, R3, R4and R5each represent H, m represents 1 and n represents 0; or
In represents CH, D represents *-CH2-N(Rf)where the asterisk indicates the bond attached to b, E represents CH2CH2CH2or, R2, R3, R4and R5each represent H, Rfrepresents H or (C1-C4)alkyl, a m and n each represent 0; or
In represents CH, D represents NRgE represents CH2CH2CH2or, R2, R3, R4R 5each represent H, Rgrepresents H, (C1-C4)alkyl or 2-hydroxyethyl and m and n each represent Oh, or a pharmaceutically acceptable salt of such compounds.

10. The compound of formula (IN) according to any one of pp.5-9, where R2, R3, R4and R5each represent H,
or pharmaceutically acceptable salt of such compounds.

11. The compound of formula (IN) of claim 10, where E represents CH2or CH2CH2;
or pharmaceutically acceptable salt of such compounds.

12. The compound of formula (IN) according to claim 11, where m denotes 0 or 1 and n denotes 0;
or pharmaceutically acceptable salt of such compounds.

13. The compound of formula (IN) according to any one of pp.5, 6, 8, or 9, where E represents CH2or CH2CH2,
or pharmaceutically acceptable salt of such compounds.

14. The compound of formula (IN) according to any one of pp.5-9, where m denotes 0 or 1, and n denotes 0,
or pharmaceutically acceptable salt of such compounds.

15. The compound of formula (IN) according to any one of pp.5-9, where G represents phenyl which is monosubstituted in position 4, or disubstituted in positions 3 and 4, where each of the substituents independently selected from the group comprising (C1-C3)alkyl, (C1-C3)alkoxygroup, floralcy is, forelcosure and halogen,
or pharmaceutically acceptable salt of such compounds.

16. The compound of formula (IN) indicated in paragraph 15, where m denotes 0 or 1 and n denotes 0,
or pharmaceutically acceptable salt of such compounds.

17. The compound of formula (IN) according to any one of pp.5, 6, 8, or 9, where
G represents 6,7-dihydro[1,4]like[2,3-C]pyridazin-3-yl; or
G represents a group selected from the group including:
,,,,
and,
where M represents CH or N, and Q and Q' independently represent O or S,
or pharmaceutically acceptable salt of such compounds.

18. The compound of formula (IN) according to any one of pp.5, 6, 8, or 9, where G represents a 2,3-dihydrobenzo[1,4]dioxin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl, 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl or 2-oxo-1,2-dihydroquinoline-7-Il,
or pharmaceutically acceptable salt of such compounds.

19. The compound of formula (IN) 17 where m denotes 0 or 1, and n denotes 0,
or pharmaceutically acceptable salt of such compounds.

20. The compound of formula (IN) according to claim 5 or its pharmaceutically acceptable salt as the medication is the main means to prevent or treat bacterial infections.

21. Pharmaceutical composition for prevention or treatment of bacterial infections comprising as active ingredient a compound of the formula (IN) according to claim 5 or its pharmaceutically acceptable salt, and at least one therapeutically inert excipient.

22. The use of the compounds of formula (IN) according to any one of pp.5-9, or its pharmaceutically acceptable salt for receiving medicines to prevent or treat bacterial infections.

23. The compound of formula (IN) according to any one of pp.5-9, or its pharmaceutically acceptable salt, for the prevention or treatment of bacterial infections.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to anhydrous crystalline vinflunine salts of general formula (I) prepared with 1 or 2 equivalents of a pharmaceutically acceptable inorganic or organic acid. . In formula (I) [The acid] represents hydrobromic, lactic or fumaric acid for a group of water-soluble crystalline salts, as well as para-toluenesulphonic, benzoic, mandelic and para-hydroxybenzoic acid for a group of relatively water-insoluble crystalline salts.

EFFECT: preparing the anhydrous crystalline vinflunine salts.

8 cl, 8 ex, 9 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel azaindole derivatives, having JAK-2 and JAK-3 kinase inhibiting activity, or pharmaceutically acceptable salts thereof. In formula (I): R3 denotes H; X1 denotes N or CR4; R2 denotes H, COOH, COOR' or CONHR'; R4 denotes H, F, R, OH, OR', COR', COOH, COOR', CONH2 or CN; or R2 and R4, taken together, form a benzene ring optionally substituted with 1-2 R10; R' denotes C1-3-alkyl or C1-3-alkenyl, each optionally substituted 1-2 R5; each R5 is independently selected from CN, unsubstituted C1-2alkyl, or two groups R5 together with a carbon atom with which they are bonded form a cyclopropyl ring; each R10 is independently selected from halogen, OCH3 or OH; R1 denotes or , R is H or denotes C1-2alkyl, optionally substituted with 1-3 R11; R6 denotes C1-4alkyl, optionally substituted with 1-5 R12; values of radicals R7 -R9, ring A, R11 -R14. The invention also relates to a pharmaceutical composition containing said compounds and a method of treating or reducing severity of a pathological condition such as allergy, asthma, amyotrophic lateral sclerosis, multiocular sclerosis, graft rejection, rheumatoid arthritis, solid malignant tumour, haematologic malignant disease, leukaemia, lymphoma and myeloproliferative disorders.

EFFECT: high efficiency of using the compounds.

41 cl, 6 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to substituted imidazopyridine derivatives of general formula (I) or enantiomers, diastereomers and tautomers and pharmaceutically acceptable salts thereof, in which A denotes -NH-, -CH2-, -CH2-CH2- or a bond; X denotes phenyl, phenyl condensed with a saturated heterocyclic 5- or 6-member ring, where the heterocyclic ring can contain one or two heteroatoms selected from O and N, and where the heterocyclic ring can further be substituted with an oxo group, a 6-member saturated heterocyclyl containing O as a heteroatom, a 5-6-member heteroaryl containing 1 or 2 heteroatoms selected from N, O and S, and where each phenyl and heteroaryl is possibly substituted with 1 to 2 R14 and/or 1 substitute R4b and/or 1 substitute R5; R1 and R2 are independently selected from the following groups: C1-6-alkyl and C1-6-alkylene-C3-7-cycloalkyl, and where each alkyl is possibly substituted with a OH group, or R1 and R2 together with the nitrogen atom with which they are bonded form a 5-6-member ring which is possibly substituted with one substitute selected from C1-6-alkyl and O-C1-6-alkyl; R4b denotes C(O)NH2, C(O)OH, C(O)NH-C1-6-alkyl, C(O)N-(C1.6-alkyl)2, SO2-C1-6-alkyl, oxo group, and where the ring is at least partially saturated, NH2, NH-C1-6-alkyl, N-(C1-6-alkyl)2; R5 denotes a 6-member heteroaryl containing N as a heteroatom; R3 denotes -(CR8R9)n-T; R8 and R9 are independently selected from the following groups: H and C1-6-alkyl; n equals 1, 2, 3, 4, 5 or 6; T denotes or NR12R13; R10 denotes H, NH2, OH, C1-6-alkyl, possibly substituted with one OH, a halogen atom, NH(C1-6-alkyl) or N(C1-6-alkyl)2; q equals 1 or 2; Y denotes CH2, NR11 or O; R11 denotes H, or C1-6-alkyl; R12 and R13 are independently selected from the following groups: H, C1-6-alkyl, C1-6-alkynyl, (CH2)0-2-C3-7-cycloalkyl, and C1-6-alkylene-O- C1-6-alkyl, where C1-6-alkyl is possibly substituted with one halogen; R14 denotes a halogen atom, CN, C1-6-alkyl, possibly substituted with 1-3 substitutes selected from halogen atom, OH, O- C1-6-alkyl, O-C(O)C1-6-alkyl, O- C1-6-alkyl, possibly substituted with one substitute selected from OH, O- C1-6-alkyl, and O-C(O) C1-6-alkyl, or OH. The invention also relates to a pharmaceutical composition based on the compound of formula (I).

EFFECT: novel imidazopyridine derivatives are obtained, which can be used as melanocortin-4 receptor modulators.

17 cl, 8 tbl, 22 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to organic chemistry, namely new compounds of formula , wherein A represents residues of formulae

, , , X represents O; X1-X4 represents N, CH, CR1 or C-, X9-X12 represents N, CH, CR4 or C-, X13-X16 represents N, CH, CR or C-, wherein C represents an attachment point of the group A to a residue of the structure of formula (I); R' represents H or alkyl; R represents alkoxy, or Het; R1 represents F, CI, Br, I, OH, CN, carboxy, CONR6R7, NR2COR8, NR2COOR8, alkoxy, fluorinated alkoxy, Ar, Het or OHet; or R1 represents one of the following formulas: wherein n is equal to 2 and m is equal to 3; R2 represents H, alkyl, fluorinated alkyl, cycloalkyl, Het or Het-NH-CO-; R4 represents F, Cl, Br, I, OH, alkoxy, cycloalkoxy, Het or OHet; or R4 represents one of the following formulae: , wherein n is equal to 2 and t is equal to 3; each R6 and R7 independently represents alkyl, or cycloalkyl, or R6 and R7 together represent alkylene group containing 5-6 carbon atoms which forms a cycle with N atoms; R8 represent alkyl, or cycloalkylalkyl; R9 represents alkyl; Ar represents aryl group; Het represents heterocyclic group which is completely saturated, particularly saturated or completely unsaturated containing 5 to 10 ring atoms in which at least 1 ring atom represents N, O or S atom which is unsubstituted or substituted once or several times by the substituted specified in cl. 1; and their pharmaceutically acceptable salts or solvates or N-oxides, or solvates of their pharmaceutically acceptable salts, or solvates of N-oxides of their pharmaceutically acceptable salts wherein said compound can be presented in the form of a polymorph, wherein if said compound shows chirality, it can be presented in the form of a mixture of enanthiomers or a mixture of diastereoisomers, or can be presented in the form of single enanthiomer or single diastereoisomer; and wherein at least one of the groups R, R1 or R4 represents Het or OHet, wherein the group Het is specified in each case in substituted or unsubstituted azabicyclooctyl, oxaazabicycloheptyl, diazabicycloheptyl, diazabicyclononyl, diazabicyclooctyl, pyrazolyl, dihydroimidazolyl, 1,4-diazepanyl, hezahydropyrrolopyrazinyl and octahydropyrrolopyridinyl. Also the invention refers to other compounds of formula (I), to specific compounds, to a pharmaceutical composition based on the compound of formula (I), to a method of selective activation/stimulation of α-7 nicotinic receptors, to application of the compound of formula (I) for making the drug.

EFFECT: there are produced new compounds showing effective biological properties.

53 cl, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present application describes substituted bicyclic beta-lactams of formula I: which are class A and class C β-lactamase inhibitors wherein X, R1 and R2 are specified in the application, as well as a method for producing them. The compounds of formula I and their pharmaceutically acceptable salts are applicable for preparing a pharmaceutical composition and for producing a drug. The declared compounds are applicable for treating bacterial infections, optionally in a combination with a β-lactam antibiotic. Particularly, the compounds may be used with such β-lactam antibiotics, as e.g. imipenem, piperacillin or ceftazidime to control microorganisms resistant to β -lactam antibiotics due to the presence of β-lactamases.

EFFECT: preparing the composition for treating bacterial infections.

28 cl, 117 ex, 3 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae

and ,

which can be used to inhibit lipid kinase, including PI3K, and treat lipid kinase-mediated disorders. Values of radicals are given in claim 1.

EFFECT: improved properties of the compound.

11 cl, 2 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formulae and including their stereoisomers, as well as pharmaceutically acceptable salt, where X denotes O or S; R1 is selected from H, F, CI, Br, I, CN, -CR14R15-NR16R17, -CR14R15-NHR10, -(CR14R15)NR10R11, -(CR14R15)nNR12C(=Y)R10, -(CR14R15)nNR12S(O)2R10, -(CR14R15)mOR10, -(CR14R15)nS(O)2R10, -C(OR10)R11R14, -C(R14)=CR18R19, -C(=Y)OR10, -C(=Y)NR10R11, -C(=Y)NR12OR10, -C(=O)NR12S(O)2R10, -C(=O)NR12(CR14R15)mNR10R11, -NHR12, -NR12C(=Y)R10, -S(O)2R10, -S(O)2NR10R11, C2-C12 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C4 carbocyclyl, piperidinyl, thiopyranyl, phenyl or C5-C6 heteroaryl; R2 is selected from H, C2-C12 alkyl and thiazolyl; R3 denotes a condensed bicyclic heteroaryl selected from indazole, indole, benzoimidazole, pyrrolopyridine, imidazopyridine and quinoline; R10, R11 and R12 independently denote H, C2-C12 alkyl, C3 carbocyclyl, heterocyclyl selected from pyrrolidine, morpholine and piperazine, phenyl or heteroaryl selected from pyrazole, pyridine, benzothiophene; or R10 and R11 together with a nitrogen atom with which they are bonded possibly form a saturated C3-C6 heterocyclic ring, possibly containing one additional ring atom selected from N or O, where said heterocyclic ring is possibly substituted with one or more groups independently selected from oxo, (CH2)mOR10, NR10R11, SO2R10, C(=O)R10, NR12S(O)R11, C(=Y)NR10R11, C1-C12 alkyl and heterocyclyl selected from pyrrolidine; R14 and R15 are independently selected from H or C1-C12 alkyl; R16 and R17 independently denote H or phenyl; R18 and R19 together with a carbon atom with which they are bonded form a C3-C20 heterocyclic ring, where said alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, piperidinyl and condensed bicyclic heteroaryl possibly substituted with one or more groups independently selected from F, CI, Br, I, CF3, -C(=Y)R10, -C(=Y)OR10, oxo, R10, -C(=Y)NR10R11, -(CR14R15)nNR10R11, -NR10R11, -NR12C(=Y)R10, -NR12C(=Y)NR10R11, -NR12SO2R10, OR10, SR10, -S(O)2R10, -S(O)2NR10R11, possibly substituted with carbocyclyl, selected from cyclopropyl, possibly substituted heterocyclyl selected from piperazine, possibly substituted with alkyl and alkylsulphonyl, pyrrolidine, morpholine, piperdine, possibly substituted CH3, phenyl and possibly substituted heteroaryl selected from imidazole and triazole; Y denotes O; m equals 0, 1 or 2; n equals 1 and t equals 2. The invention also relates to a pharmaceutical composition which modulates lipid kinase activity, based on said compounds.

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used to treat lipid kinase-mediated diseases, for example, cancer.

48 cl, 2 tbl, 372 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula where R1 is selected from H, F, CI, Br, CF3, C1-C6 alkoxy and OH; R2 is selected from H and C1-C6 alkyl; n equals 1-5; m equals 0 or 1; and Y is selected from CH2, NR3, (NR3R4)+X-, O and S; R3 and R4 are independently selected from H and C1-C4 alkyl; and X- is selected from pharmaceutically acceptable anions. The invention also relates to a method of producing said compound and to an antiviral pharmaceutical composition based on said compound of formula (I).

EFFECT: obtaining novel compounds and a composition based on said compounds, which can be used in medicine to treat a viral diseases such as herpes.

19 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: described is a compound of general formula: [1], where R1 denotes an optionally substituted C2-C12 alkyl, aryl or heterocyclic group which can be a mono- or bicyclic 5-11-member radical, where the heteroatoms can be nitrogen, oxygen or sulphur; X1 denotes C2-C4 an alkylene group; X2 denotes a bond; X3 denotes a group of general formula NR3 or CR4R5NR3 (where R3 denotes a hydrogen atom, optionally substituted lower alkyl group or imino-protective group) and R4 and R5 are identical or different, and each denotes a hydrogen atom or a lower alkyl group or bond; X4 denotes a lower alkylene or lower alkenylene or lower alkynylene group, which can be substituted with one or more oxo groups or a bond; X5 denotes a sulphur atom or bond; Y1 denotes an optionally substituted divalent 4-, 5- or 6-member alicyclic hydrocarbon residue or an optionally subsituted divalent 5- or 6-member alicyclic amine residue, where the heteroatoms can be nitrogen or oxygen; Z1, Z2, Z3, Z4, Z5 and Z6 are identical or different, and each denotes a nitrogen atom or a group of general formula CR7 (where R7 denotes a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted amino group, or an amino group substituted with one or more C1-6 alkyl groups, a lower alkyl group, a cycloalkyl, a lower alkoxy group or a monocyclic 5-member heterocyclic group which can be substituted with one or more halogen atoms, where the heteroatoms can be nitrogen, acid or sulphur or a group of general formula Q1CO2R10 (where R10 denotes a carboxyl-protective group and Q1 denotes a lower alkenylene group), provided that at least one of Z3, Z4, Z5 and Z6 denotes a nitrogen atom, or salt thereof. The invention also describes an antimicrobial agent based on said compound.

EFFECT: novel compounds which can be used as antimicrobial agents are obtained and described.

25 cl, 176 ex, 6 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel crystalline form of vinflunine ditartrate, production method thereof and use thereof in therapy, especially for cancer pathology treatment.

EFFECT: high stability and wide variety of galenic forms.

8 cl, 3 ex, 5 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazopyridine compounds of formula (I) and pharmaceutically acceptable salts thereof, which inhibit kinase activity, selected from IGF-1R, IR, EGFR and Erb2 and have cell proliferation inhibitor properties. In formula (I) halogeno denotes a halogen; X1 is H or halogen, R1 is H, halogen or halogen-C1-C4alkyl; R2 is H or O-C1-C4alkyl; each R3 is identical or different and is independently selected from H, halogen, C1-C4alkyl, halogen-C1-C4alkyl and O-C1-C4alkyl; one of R4 and R5 is selected from H, halogen, C1-C4alkyl and O-C1-C4alkyl; and the other is a group selected from: (i), (ii) and (iii) where:(1) each R7 is H; a equals 0, 1, 2 or 3; R8 is selected from NH2, N(H)C1-C4alkyl, N(C1-C4alkyl)2 and a group of formula (iv): (iv), where: ring D is a 5-6-member saturated N-heterocycle, possibly containing 1 or 2 additional heteroatoms selected from N and O. Other values of radicals are given in the claim.

EFFECT: compounds can be used in treating different types of cancer.

4 tbl, 250 ex

Chemical compounds // 2469034

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention describes compounds of formula (I) wherein: R1 means C1-6alkyl or C3-6cycloalkyl; wherein R1 may be optionally carbon-substituted by one or more R6; R2 means hydrogen; R3 and R4 are carbon substitutes, and each is independently specified in carboxy, carbamoyl, N-(C1-6alkyl)amino, N,N-(C1-6alkyl)2amino, C1-6alkanoylamino, N-(C1-6alkyl)carbamoyl, N,N-(C1-6alkyl)2carbamoyl, N-(C1-6alkoxy)carbamoyl, phenyl-R9 - or heterocyclyl-R10-; wherein R3 and R4 may be independently carbon-substituted by one or more R11; and wherein provided said heterocyclyl contains -NH - residue, then nitrogen may be optionally substituted by a group specified in R12; m has the value of 0, 1 or 2; wherein the values R3 may be equal or different; p has the value of 0, 1 or 2; wherein the values R4 may be equal or different; the ring A means nitrogen-containing 5- or 6-member heterocyclic group; wherein drawn nitrogen represents = N- and is found in an ortho-position to R1R2NC(O)NH group in formula (I); the ring B means phenyl or heterocyclyl; wherein provided said heterocyclyl contains -NH- residue, then nitrogen may be optionally substituted by a group specified in R14; R5 is specified in hydroxy, C1-6alkoxy or -N(R15)(R16); R6 and R11 are carbon substitutes and each is independently specified in halo, C1-6alkyl or C1-6alkoxy; R15 and R16 are independently specified in hydrogen, C1-6alkyl, C1-6alkoxy, cyclopropyl or cyclopentyl; R12 and R14 mean C1-6alkyl; wherein R14 may be optionally carbon specified by one or more R23; R9 and R10 mean a direct link; and R23 means halo or methoxy; wherein said heterocyclyl means pyridine, imidazole, triazole, thiazole, benzothiazole, imodazolepyridine, dihydroquinoline or thiadiazole, or its pharmaceutically acceptable salt; provided said compound represents other than ethyl ester of 5-[2-[[(ethylamino)carbonyl]amino]pyridin-4-yl]-4-methyl-4H-1,2,4-triazole-3-carboxylic acid or their pharmaceutically acceptable salts. There are also described pharmaceutical compositions on the basis of said compounds, a method for bacterial DNA-hydrase and/or bacterial topoisomerase IV inhibition in a homoiothermal animal, as well as a method of treating an infection in a homoiothermal animal.

EFFECT: there are prepared and described new compounds showing antibacterial activity.

24 cl, 165 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to fluorinated compounds of formula , where: D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more halogen atoms; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: halogen, C1-C10 alkyl; E denotes aryl which can be substituted with one or more fluoro-substitutes or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more fluoro-substitutes, and where Q denotes O; m denotes a number from 1 to 2; under the condition that: R3 is a fluoro-substitute, or group E includes a fluoro-substitute, or group Z includes a fluoro-substitute, with the condition that E does not denote 4-fluorophenyl or a compound of formula , where D, G and L are independently selected from a group consisting of: CH, C and N, and J and M are independently selected from a group consisting of C and N, under the condition that one of J and M denotes C and the other denotes N, wherein at least two of D, G, M, J and L denote N; X denotes CH2; Y is absent; Z denotes NR1R2; R1 and R2 are independently selected from a group consisting of: hydrogen, C1-C10 alkyl, aryl and heteroaryl, which is associated with aromatic radicals having 6 ring atoms, where 1-2 of these ring atoms are N; each of which can be substituted with one or more of the following substitutes: chlorine, bromine, iodine; or R1 and R2, together with nitrogen to which they are bonded, form a heterocyclic ring having 5 ring members; R3 is selected from a group consisting of: chlorine, bromine, iodine, C1-C10 alkyl; E denotes aryl which can be substituted with one or more chlorine, bromine or iodine atoms, and/or one or more of the following substitutes: C1-C6 alkyl, QC1-C10 alkyl, QC2-C10 alkenyl, each of which can be substituted with one or more substitutes selected from chlorine, bromine, iodine or hydroxy, where Q denotes O, wherein when E denotes phenyl, E does not contain, as a substitute, iodine which is directly bonded to it at position 4; m denotes a number from 1 to 2; wherein at least one of Z, E and R3 includes iodine; under the condition that E does not denote 4-iodophenyl and under the condition that said compound is not a compound of formula (Ia), defined in the following table:

The invention also relates to a pharmaceutical composition based on the compound of formula (I) or (Ia), a diagnosis method, a method of treating said disorders, based on use of the compound of formula (I) or (Ia), and use of the compound of formula (I) or (Ia).

EFFECT: obtaining novel compounds useful in treating disorders in mammals, characterised by anomalous density of peripheral benzodiazepine receptors.

24 cl, 13 dwg, 9 tbl, 23 ex

FIELD: chemistry.

SUBSTANCE: compounds, which have formula I , in which A, B, R1, R1a, R2, R3, R4, R5 R6, R7 and R8 have values given in description and are inhibitors of receptor tyrosinkinases, useful in treatment of diseases, mediated by class 3 and class 5 receptor tyrosinkinases. It has been also discovered that specific compounds of the claimed invention are Pim-1 inhibitors. Also claimed is method of obtaining formula I compound.

EFFECT: increase of compound efficiency.

27 cl, 51 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of [1,8]naphthyridine, described by formula I(a), where Z represents -NR41-; A represents phenyl; each R10, R17, R31, R33, R35 and R41 in each case is independently selected from group, consisting of hydrogen, C1-C6alkyl, C1-C6haligenalkyl, phenyl, C3-C6cycloalkyl, -Ls-O-Rs, -Ls-C(O)Rs, -Ls-C(O)ORs and LE-Q-LE-(morpholine); X is selected from group, consisting of bond, -Ls-O-, -Ls-S- and -Ls-C(O)N(Rs)-; R22 is selected from group, consisting of halogen, C1-C6alkyl, phenyl, and phenyl C1-C2alkyl, and, optionally, is substituted with one R26, where R26 in each case is independently selected from group, consisting of halogen, hydroxy, nitro, C1-C6alkyl, -Ls-OSO2Rs; Y is selected from group, consisting of bond, -Ls-O-, -Ls-S(O)-, -Ls-C(O)N(R15) - and -Ls-S-, where R15 represents hydrogen; R50 represents -L1-A1, where A1 is selected from group, consisting of C1-C6alkyl and phenyl and L1 is selected from group, consisting of bond and C1-4alkylene, where A1 is optionally substituted with from one to three R30, and R30 in each case is independently selected from group, consisting of halogen, hydroxy, amino, azido, C1-C6alkyl, -Ls-O-Rs, -Ls-C(O)ORs, -LS-N(RSRS), -Ls-C(=NRs)RS', -Ls-C(O)N(RsRsO, -Ls-N(Rs)C(O)Rs', -LE-Q-LE'- (phenyl or naphthyl) and -LE-Q-LE'-(M5-M6heterocyclyl, which represents pyridine, pyrazine, pyrrolodine, furan, thiophene, piperidine); Ls in each case is independently selected from group, consisting of bond and C1-4alkylene; each RS and Rs' in each case is independently selected from group, consisting of hydrogen, C1-C6alkyl, C3-6alkenyl, C1-6alkoxy, C1-6alkoxyC1-C6alkyl and C1-6alkoxycarbonylC1-C6alkyl; each LE and LE' in each case is independently selected from group, consisting of bond, C1-4alkylene, -C1-4alkylene-NC(O)-C1-4alkylene-; Q in each case is independently selected from group, consisting of bond, -O-, -N(Rs)C(O)-, -C(O)N(Rs)- and -O-SO2-; each R17 and R30 in each case is optionally independently substituted with from one to three substituent(s), selected from group, consisting of halogen and hydroxy; and each heterocyclyl group in -LE-Q-LE'-(M5-M6heterocyclyl) in each case is optionally independently substituted with at least one or two substituents, selected from group, consisting of hydrogen, hydroxy, C1-C6alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, phenyloxy and phenylC1-6alkoxycarbonyl, or to their pharmaceutically acceptable salts. Invention also relates to compounds of formula II(a), pharmaceutical composition based on claimed compounds, application of claimed compounds, method of inhibition of HCV virus replication, method of treating HCV infection.

EFFECT: obtained are novel derivatives, useful in treatment of HCV infection.

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of dihydroquinone and dihydronaphthyridinone of formula (I) or to its pharmaceutically acceptable salts, in which X represents group CR11 or N; Y represents group -C(O)R3, oxazolyl or isoxazolyl; Z represents phenyl, pyrrolidinyl, piperidinyl, morpholinyl, tetrahydropyranyl, pyridinyl, pyrimidinyl or pyrazolyl, and is substituted with groups R1 and R2; R1 and R2 each independently represents H, halogen, CN group, C1-6alkyl or group -Y1-Y2-Y3-R8, or R1 and R2 together form group -O(CH2)nO-, where n represents 1 or 2; Y1 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O), -S-, -SO2- or bond; Y2 represents heterocycloalkylene, C1-6alkylene or bond, where heterocycloalkylene stands for cycloalkylene group, in which one, two carbon atoms are substituted with heteroatoms O or N, where heterocycloalkylene group also contains, at least, two carbon atoms and cycloalkylene represents ; Y3 represents group -O-, -C(O)-, -C(O)O-, -C(O)NR9-, -NR9C(O)-, -SO2- or bond; R8 represents H, C1-6alkyl, C1-6alkoxy, cyclohexyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, tetrahydropyranyl, or group -NR9R10, where R8, different from H, is optionally substituted with C1-6alkyl, halogen, group -CF3 or group -OH; R9 and R10 each independently represents H or C1-6alkyl; R3 represents OH, C1-6alkyl, C1-6alkoxy, (C1-6alkoxy)-C1-6alkoxy; R4 represents C1-6alkyl, phenyl, cyclopropyl, cyclobutyl, cyclobutyl, cyclohexyl, tetrahydropyranyl or tetrahydrothiophene 1,1 -dioxide, and is optionally substituted with C1-6alkyl, hydroxyl group, C1-6alkoxy, halogen, nitro group, amino group, cyano group or halo-lower alkyl; R5 and R6 each independently represents H, halogen, C1-6alkyl, group -CF3, C1-6alkoxy; R7 represents H; R11 represents H. Invention also re4lates to pharmaceutical composition based on formula (I) compound.

EFFECT: obtained are novel dihydroquinone and dihydronaphthyridinone derivatives, useful for treatment of disease mediated by JNK kinase.

9 cl, 4 tbl, 38 ex

FIELD: medicine.

SUBSTANCE: invention refers to an agent for activation of lipoprotein lipase containing a benzene derivative of general formula (1) which is used for preventing and treating hyperlipidemia and obesity. The invention also refers to the benzene derivatives of general formula (1a).

EFFECT: composition improvement.

8 cl, 6 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new compounds of general formula 1:

wherein Q, X1, X2, Y, Z, R1, R2, R3, R3', R4, R4', R5, R6, R6' have the values specified in the description.

EFFECT: compounds are the IAP inhibitors which can be used as therapeutic agents for malignant diseases.

13 cl, 20 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new bicyclic heterocyclic derivatives of general formula wherein radicals and symbols are specified in the patent claim. Said compounds are FGFR receptor (fibroblast growth factor receptor) inhibitors. The invention also refers to a method for preparing a preferential group of compounds of formula (I), to a pharmaceutical composition containing said compounds, and to the use of said compounds for treating diseases, e.g. cancer.

EFFECT: preparing the new bicyclic heterocyclic derivatives.

22 cl, 16 tbl, 422 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel bicyclic heterocyclic derivatives, which are compounds of formula where values of X1-X5, A, B, R1, R2, q are given in claim 1, as well as pharmaceutical compositions containing said compounds, and use of said compounds to treat cancer.

EFFECT: high efficiency of treatment.

22 cl, 43 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention describes specific compounds, namely pyridyl-piperidine compounds, which represent antagonists of orexin receptors and can be used for treatment or prevention of neurologic and psychiatric disorders and diseases, in development of which orexin receptors participate.

EFFECT: claimed invention relates to pharmaceutical compositions, containing said compounds, as well as to application of said compounds and compositions for prevention or treatment of diseases, in development of which orexin receptors participate.

5 cl, 1 ex, 2 tbl

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