5-aminocyclylmethyl-oxazolidin-2-one derivatives

1. A compound of formula I

wherein

one or two of U, V, W, and X represent N, the rest represent CH or, in the case of X, may also represent CR a wherein R a is fluorine;

R 1 represents alkoxy, halogen or cyano;

R 2 represents H, CH 2 OH, CH 2 N 3 , CH 2 NH 2 , alkylcarbonylaminomethyl or triazol-1-ylmethyl;

R 3 represents H, or, when n is 1, R 3 may also represent OH, NH 2 , NHCOR 6 or triazol-1-yl;

A represents CR 4 ;

K represents O, NH, OCH 2 , NHCO, NHCH 2 , CH 2 NH, CH 2 CH 2 , CH═CH, CHOHCHOH or CHR 5 ;

R 4 represents H or together with R 5 forms a bond, or also R 4 can represent OH when K is not O, NH, OCH 2 or NHCO;

R 5 represents OH or together with R 4 forms a bond;

R 6 represents alkyl;

m is 0 or 1 and n is 0 or 1; and

G represents the group

wherein 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 CH, and Z 3 represents CH or N;

and the ring P is selected from the following:

in which Q is O or S;

or a salt thereof.

2. The compound of formula I according to claim 1 , wherein

R 1 represents alkoxy;

R 3 represents H, or, when n is 1, R 3 may also represent OH, NH 2 or triazol-1-yl;

K represents O, NH, OCH 2 , NHCO, NHCH 2 , CH 2 CH 2 , CH═CH, CHOHCHOH or CHR 5 , and

G represents the group

wherein Z is N or CH;

or a salt thereof.

3. The compound of claim 1 , wherein R 1 is methoxy;

or a salt thereof.

4. The compound of formula I according to claim 1 , wherein

U and V each represent N and W and X each represent CH,

U and V each represent CH and W and X each represent N, or

U and W each represent N and V and X each represent CH;

or a salt thereof.

5. The compound of formula I according to claim 1 wherein m and n are each 0;

or a salt thereof.

6. The compound of formula I according to claim 1 wherein m is 1 and n is 0;

or a salt thereof.

7. The compound of formula I according to claim 1 wherein G is 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-yl;

or a salt thereof.

8. The compound of formula I according to claim 1 wherein the compound is:

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

6-{(R)-5-[(R)-3-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[(S)-3-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-[3-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-oxazolidin-2-one;

6-{(R)-5-[(2S,4S)-2-hydroxymethyl-4-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[(2S,4S)-2-azidomethyl-4-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-azetidine-3-carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;

1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-pyrrolidine-3-carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;

6-((R)-5-{3-[(E)-2-(6-methoxy-[1,5]naphthyridin-4-yl)-vinyl]-pyrrolidin-1-ylmethy}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-((R)-5-{3-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-pyrrolidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-((R)-5-{3-[(1R,2R)-1,2-dihydroxy-2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-pyrrolidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[4-(3-methoxy-quinoxalin-5-ylmethylene)-piperidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

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

6-((R)-5-{3-[(6-methoxy-[1,5]naphthyridin-4-ylamino)-methyl]-azetidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[(2S,4S)-2-aminomethyl-4-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[(3R*,4R*)-3-(6-methoxy-quinazolin-4-yloxy)-4-[1,2,3]triazol-1-yl-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

N-{(2S,4S)-4-(6-methoxy-quinazolin-4-yloxy)-1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-pyrrolidin-2-ylmethyl}-acetamide;

6-{(R)-5-[(3R*,4R*)-3-amino-4-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[(2S,4S)-4-(6-methoxy-quinazolin-4-yloxy)-2-[1,2,3]triazol-1-ylmethyl-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[4-(6-methoxy-quinazolin-4-yloxy)-piperidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[(3R*,4S*)-3-hydroxy-4-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one; or

6-{(R)-5-[(3R*,4R*)-3-hydroxy-4-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

or a salt thereof.

9. The compound of formula I according to claim 1 wherein the compound is:

6-{(R)-5-[3-(3-fluoro-6-methoxy-[1,5]naphthyridin-4-ylamino)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;

6-{(R)-5-[3-(6-methoxy-[1,5]naphthyridin-4-ylamino)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;

6-{(R)-5-[3-(6-methoxy-quinolin-4-ylamino)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;

6-((R)-5-{3-[(3-fluoro-6-methoxy-[1,5]naphthyridin-4-ylmethyl)-amino]-azetidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one;

6-((R)-5-{3-[(6-methoxy-[1,5]naphthyridin-4-ylmethyl)-amino]-azetidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one;

6-((R)-5-{3-[(3-fluoro-6-methoxy-quinolin-4-ylmethyl)-amino]-azetidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one;

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

(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-[3-(6-methoxy-quinazolin-4-yloxymethyl)-azetidin-1-ylmethyl]-oxazolidin-2-one;

6-{(R)-5-[4-(6-methoxy-quinazolin-4-yloxy)-piperidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;

N-{(3R*,4R*)-4-(6-methoxy-quinazolin-4-yloxy)-1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-pyrrolidin-3-yl}-acetamide;

(R)-3-(6,7-dihydro-[1,4]dioxino[2,3-c]pyridazin-3-yl)-5-[3-(6-methoxy-quinazolin-4-yloxy)-pyrrolidin-1-ylmethyl]-oxazolidin-2-one;

6-((R)-5-{3-[(3-methoxy-quinoxalin-5-ylmethyl)-amino]-azetidin-1-ylmethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]oxazin-3-one;

6-{(R)-5-[4-(6-methoxy-[1,5]naphthyridin-4-ylamino)-piperidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;

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

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

4-{1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-azetidin-3-ylamino}-quinoline-6-carbonitrile;

6-{(R)-5-[3-(6-fluoro-quinolin-4-ylamino)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

6-{(R)-5-[4-(6-methoxy-[1,5]naphthyridin-4-ylamino)-piperidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;

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

(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-[3-(6-methoxy-[1,5]naphthyridin-4-ylamino)-azetidin-1-ylmethyl]-oxazolidin-2-one;

6-{(R)-5-[3-(6-fluoro-quinolin-4-ylamino)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one; or

(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-[3-(6-methoxy-quinolin-4-yloxy)-azetidin-1-ylmethyl]-oxazolidin-2-one;

or a salt thereof.

10. A pharmaceutical composition comprising as an active principal the compound of formula I according to claim 1 or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

11. A method of treating a bacterial infection comprising the administration of a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

12. A method of treating a bacterial infection comprising the administration of a therapeutically effective amount of the composition of claim 10 .