Azatricyclic antibiotic compounds

1. A compound of formula I

wherein

n is 0 or 1;

R 1 represents H or F;

U represents CH 2 or, provided n is 1, O or NH;

“-----” is a bond or is absent;

V represents CH or N when “-----” is a bond, or V represents CH 2 or NH when “-----” is absent;

W represents CH or N;

A is —(CH 2 ) p —NH—(CH 2 ) q — wherein p is 1 and q is 1 or 2 or, provided U represents CH 2 and n is 1, p may also be 0 and q is then 2;

G represents one of the groups G 1 and G 2 represented below

wherein

Z represents N or CH and Q represents O or S; and

Z 0 , Z 1 and Z 2 each represent CH, or Z 0 and Z 1 each represent CH and Z 2 represents N, or Z 0 represents CH, Z 1 represents N and Z 2 represents CH or N, or Z 0 represents N and Z 1 and Z 2 each represent CH;

or a salt of such a compound.

2. The compound according to claim 1 of formula I P1

wherein

n is 0 or 1;

R 1 represents H or F;

U represents CH 2 or, provided n is 1, O;

W represents CH or N;

A is —(CH 2 ) p —NH—(CH 2 ) q —wherein p is 1 and q is 1 or 2 or, provided U represents CH 2 and n is 1,

p may also be 0 and q is then 2;

G represents one of the groups G 1 and G 2 ′ represented below

wherein Z, Z 1 and Z 2 each independently represent N or CH and Q represents O or S;

or a salt of such a compound.

3. A compound of formula I according to claim 1 , wherein W represents CH;

or a salt of such a compound.

4. A compound of formula I according to claim 1 , wherein W represents N;

or a salt of such a compound.

5. A compound of formula I according to claim 1 , wherein R 1 represents F;

or a salt of such a compound.

6. A compound of formula I according to claim 1 , wherein U represents O;

or a salt of such a compound.

7. A compound of formula I according to claim 1 , wherein U represents CH 2 ;

or a salt of such a compound.

8. A compound of formula I according to claim 1 , wherein G represents the group G 1 and Z represents CH;

or a salt of such a compound.

9. A compound of formula I according to claim 2 , wherein G represents the group G 2 or G 2 ′;

or a salt of such a compound.

10. A compound of formula I according to claim 1 , which is:

-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-2,3-dihydro-1-oxa-3 a, 7-diaza-phenalen-4-one;

-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-2,3-dihydro-1-oxa-3 a, 7-diaza-phenalen-4-one;

-8-fluoro-6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin -5-ylmethyl]-amino}-methyl)-6,7-dihydro-5H-pyrido[3,2,1-ij]quinolin-3-one;

-8-fluoro-6-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin -5-ylmethyl]-amino}-methyl)-6,7-dihydro-5H-pyrido[3,2,1-ij]quinolin-3-one;

-6-({[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-amino}-methyl) -8-fluoro-6,7-dihydro-5H-pyrido[3,2,1-ij]quinolin-3-one;

-(R)-9-fluoro-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro -2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo [3,2,1-ij]quinolin-4-one;

-8-fluoro-6-{2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-6,7-dihydro-5H-pyrido[3,2,1-ij]quinolin-3-one;

-(R)-9-fluoro-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-9-fluoro-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]amino}-methyl)-1,2-dihydro-pyrrolo [3,2,1-ij]quinolin-4-one ;

-(R)-9-fluoro-2-({2-[2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-2,3-dihydro-1 -oxa-3a-aza-phenalen-4-one;

-9-fluoro-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-2,3-dihydro-1-oxa-3 a -aza-phenalen-4-one;

-3-fluoro-5-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-5,6-dihydro-4H-1,6 a -diaza-phenalen-7-one;

-3-fluoro-5-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethy]-amino}-methyl)-5,6-dihydro-4H-1,6 a -diaza-phenalen-7-one;

-3-fluoro-5-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;

-(S)-9-fluoro-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)- 1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-(S)-9-fluoro-2-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-(R)-9-fluoro-2-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)- 1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-(S)-9-fluoro-2-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-(R)-9-fluoro-2-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-9-fluoro-2-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1 -ij]quinolin-4-one;

-9-fluoro-2-{2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1 -ij]quinolin-4-one;

-9-fluoro-2-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl-oxazolidin-5-yl]-ethylamino}-methyl)-1,2,5,6-tetrahydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-5-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;

-5-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-4,5-dihydro-pyrrolo[3,2,1-de][1,5]naphthyridin-7-one;

-2-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-2-({2-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)- 1,2-dihydro-pyrrolo [3,2,1-ij]quinolin-4-one;

-2-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1 ,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-amino}-methyl)-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;

-(S)-5-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;

-(S)-5-({[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)oxazolidin-5-ylmethy]-amino}-methyl)-5,6-dihydro-pyffolo[1,2,3-de]quinoxalin-3-one; or

-5-({2-[(S)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-oxazolidin-5-yl]-ethylamino}-methyl)-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;

or a salt of such a compound.

11. A pharmaceutical composition comprising, as active principle, a compound of formula I as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

12. A method for treating a bacterial infection comprising administering a compound of formula I as defined in claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.

13. 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 or prevent a bacterial infection and at least one therapeutically inert excipient.

14. A compound of formula I P1 according to claim 2 , wherein W represents CH;

or a salt of such a compound.

15. A compound of formula I P1 according to claim 2 , wherein W represents N;

or a salt of such a compound.

16. A compound of formula I P1 according to claim 2 , wherein R 1 represents F;

or a salt of such a compound.

17. A compound of formula I P1 according to claim 2 , wherein U represents O;

or a salt of such a compound.

18. A compound of formula I P1 according to claim 2 , wherein U represents CH 2 ;

or a salt of such a compound.

19. A compound of formula I P1 according to claim 2 , wherein G represents the group G 1 and Z represents CH;

or a salt of such a compound.

20. A compound of formula I P1 according to claim 2 , wherein G represents the group G 2 or G 2 ′;

or a salt of such a compound.

21. A pharmaceutical composition comprising a compound of formula I P1 as defined in claim 2 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

22. A method for treating a bacterial infection comprising administering a compound of formula I P1 as defined in claim 2 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof.