Oxazolidinone derivatives

1. A compound of Formula (I)

wherein

is a bond or is absent;

R 1 represents (C 1 -C 4 )alkoxy or halogen;

R 1b represents H or (C 1 -C 3 )alkyl;

U and V each independently represent CH or N;

W represents CH or N, or, in case is absent, W represents CH 2 or NH;

with the proviso that at least one of U, V and W represents CH or CH 2 ;

A represents —CH 2 —CH(R 2 )-B-NH—* or —CH(R 3 )—CH 2 —N(R 4 )—[CH 2 ] m —*; wherein the asterisks indicate the bond which is linked via the CH 2 -group to the oxazolidinone moiety;

B represents CH 2 or CO; and

R 2 represents hydrogen, OH or NH 2 ;

R 3 and R 4 both represent hydrogen, or R 3 and R 4 together form a methylene bridge;

m represents the integer 0, 1 or 2; and

G represents phenyl which is mono-substituted in position 3 or 4, or disubstituted in positions 3 and 4, wherein each substituent is independently (C 1 -C 4 )alkyl, (C 1 -C 3 )alkoxy or halogen; or

G represents G 1 , G 2 , G 3 , G 4 , G 5 or G 6 drawn below:

wherein

M represents CH or N;

Q and Q′ independently represent S or 0;

Z 1 represents N, Z 2 represents CH, and Z 3 represents CH; or

Z 1 represents CH, Z 2 represents N, and Z 3 represents CH or N; or

Z 1 represents CH, Z 2 represents CR 5 , and Z 3 represents CH; or

Z 1 represents CH, Z 2 represents CH, and Z 3 represents N; and

R 5 represents hydrogen or fluorine;

or a salt of such a compound.

2. A compound of Formula (I) according to claim 1 , wherein R 1b represents H and m, if present, represents 1 or 2;

or a salt of such a compound.

3. The compound according to claim 1 of formula (I P1 )

wherein

R 1 represents (C 1 -C 4 )alkoxy or halogen;

U represents CH or N;

V represents CH;

W represents CH or N;

A represents —CH 2 —CH(R 2 )-B-NH—* or —CH(R 3 )—CH 2 —N(R 4 )—CH 2 —*; wherein the asterisks indicate the bond which is linked via the CH 2 -group to the oxazolidinone moiety;

R 2 represents hydrogen, OH or NH 2 ;

R 3 and R 4 together represent CH 2 ;

B represents CH 2 or CO; and

G represents 6,7-dihydro-[1,4]dioxino[2,3-d]pyridazin-3-yl; or

wherein

M and Z 1 represent CH or N; and

Q and Q′ independently represent S or O;

or a salt of such a compound.

4. A compound of Formula (I) according to claim 1 , wherein the stereocenter at position 5 of the oxazolidin-2-one ring is in (R)-configuration or a salt of such a compound.

5. A compound of Formula (I) according to claim 1 , wherein U, V and W each represent CH, or U and V each represent CH and W represents N, or U and W each represent N and V represents CH;

or a salt of such a compound.

6. A compound of Formula (I) according to claim 1 , wherein R 1 represents (C 1 -C 4 )alkoxy;

or a salt of such a compound.

7. A compound of Formula (I) according to claim 1 , wherein A represents —CH 2 —CH(R 2 )-B-NH—*;

or a salt of such a compound.

8. A compound of Formula (I) according to claim 7 , wherein B represents CH 2 and R 2 represents hydrogen or OH;

or a salt of such a compound.

9. A compound of Formula (I) according to claim 1 , wherein A represents —CH(R 3 )—CH 2 —N(R 4 )—[CH 2 ] m —* wherein R 3 and R 4 together form a methylene bridge and m represents the integer 1 or 2;

or a salt of such a compound.

10. A compound of Formula (I) according to claim 1 , wherein G represents a group selected from 3-fluoro-4-methyl-phenyl, 4-ethoxy-phenyl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl and 7-fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl;

or a salt of such a compound.

11. A compound of Formula (I) according to claim 1 selected from the following compounds:

6-((R)-5-{[3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-propylamino]-methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-((R)-5-{[3-(7-bromo-2-oxo-2H-quinolin-1-yl)-propylamino]-methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

1-(3-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-propyl)-7-methoxy-1H-quinolin-2-one;

7-bromo-1-(3-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-propyl)-1H-quinolin-2-one;

6-(5-{2-[3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-azetidin-1-yl]-ethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

3-(7-methoxy-2-oxo-2H-quinoxalin-1-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-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-propionamide;

3-(7-bromo-2-oxo-2H-quinolin-1-yl)-N-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-propionamide;

3-(7-bromo-2-oxo-2H-quinolin-1-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-dihydro-benzo[,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-3-(7-methoxy-2-oxo-2H-quinoxalin-1-yl)-propionamide;

3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-N-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-propionamide;

(S)-2-amino-N-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-3-(7-methoxy-2-oxo-2H-quinoxalin-1-yl)-propionamide;

(R)-2-amino-N-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-3-(7-methoxy-2-oxo-2H-quinoxalin-1-yl)-propionamide;

6-((R)-5-{[(R)-2-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-propylamino]-methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one;

6-((R)-5-{[(R)-2-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-propylamino]-methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-((R)-5-{[(S)-2-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-propylamino]-methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

7-fluoro-6-((R)-5-{[(S)-2-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-yl)-propylamino]-methyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-methoxy-4-(3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-propyl)-4H-pyrido[2,3-b]pyrazin-3-one;

4-(3-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-propyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-(3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-propyl)-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-(2-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-ethyl)-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-(2-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-ethyl)-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-(1-{2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-azetidin-3-yl)-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-(1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propyl}-azetidin-3-yl)-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-(1-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethyl}-azetidin-3-yl)-4H-pyrido[2,3-b]pyrazin-3-one;

4-((R)-2-hydroxy-3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-propyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one;

4-((R)-3-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-2-hydroxy-propyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one;

4-((R)-2-hydroxy-3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-propyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one; and

1-(3-{[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-propyl)-7-methoxy-3,4-dihydro-1H-quinolin-2-one;

4-(3-{[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-propyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one;

6-methoxy-4-{1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-azetidin-3-yl}-4H-pyrido[2,3-b]pyrazin-3-one;

4-(2-{2-[3-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-ethyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one;

4-(2-{2-[3-(2,3-dihydro-[1,4]-dioxino[2,3-b]pyridin-6-yl)-2-oxo-oxazolidin-5-yl]-ethylamino}-ethyl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one;

6-(5-{2-[2-(6-methoxy-3-oxo-3H-pyrido[2,3-b]pyrazin-4-yl)-ethylamino]-ethyl}-2-oxo-oxazolidin-3-yl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;

4-(1-{2-[(R)-3-(4-ethoxy-phenyl)-2-oxo-oxazolidin-5-yl]-ethyl}-azetidin-3-yl)-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one; or

6-methoxy-2-methyl-4-(3-{[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-propyl)-4H-pyrido[2,3-b]pyrazin-3-one:

or a salt of such a compound.

12. A pharmaceutical composition comprising, as active principle, compound of Formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

13. A method for treating a bacterial infection comprising administering a compound of Formula (I) according to claim 1 , or of a pharmaceutically acceptable salt thereof to a subject in need thereof.

14. A composition comprising the compound of Formula I as defined in claim 1 , or a pharmaceutically acceptable salt thereof, in an amount effective to treat a bacterial infection and at least one therapeutically inert excipient.

15. A compound of Formula (I P1 ) according to claim 3 , wherein the stereocenter at position 5 of the oxazolidin-2-one ring is in (R)-configuration or a salt of such a compound.

16. A compound of Formula (I P1 ) according to claim 3 , wherein U, V and W each represent CH, or U and V each represent CH and W represents N, or U and W each represent N and V represents CH;

or a salt of such a compound.

17. A compound of Formula (I P1 ) according to claim 3 , wherein R 1 represents (C 1 -C 4 )alkoxy;

or a salt of such a compound.

18. A compound of Formula (I P1 ) according to claim 3 , wherein A represents —CH 2 —CH(R 2 )-B-NH—*;

or a salt of such a compound.

19. A compound of Formula (I P1 ) according to claim 17 , wherein B represents CH 2 and R 2 represents hydrogen or OH;

or a salt of such a compound.

20. A compound of Formula (I P1 ) according to claim 3 , wherein A represents —CH(R 3 )—CH 2 —N(R 4 )—[CH 2 ] m —* wherein in R 3 and R 4 together form a methylene bridge and m represents the integer 1 or 2;

or a salt of such a compound.

21. A compound of Formula (I P1 ) according to claim 3 , wherein G represents 3-fluoro-4-methyl-phenyl, 4-ethoxy-phenyl, 2,3-dihydro-benzo[1,4]dioxin-6-yl, 2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl, 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-yl, 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl or 7-fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl;

or a salt of such a compound.

22. A pharmaceutical composition comprising a compound of Formula (I P1 ) according to claim 3 or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

23. A method for treating a bacterial infection comprising administering a compound of Formula (I P1 ) according to claim 3 , or of a pharmaceutically acceptable salt thereof.