Tricyclic oxazolidinone antibiotic compounds

1. A compound of formula I

wherein

“-----” is a bond or is absent;

R 0 represents H or, in the case “-----” is a bond, may also represent (C 1 -C 3 )alkoxy;

R 1 represents cyano, (C 1 -C 3 )alkyl, or ethynyl;

U represents CH or N when “-----” is a bond, or, in case “----” is absent, U represents CH 2 , NH or NR 9 ;

V represents CH, CR 6 , or N;

R 2 represents H, (C 1 -C 3 )alkylcarbonyl or a group of the formula —CH 2 —R 3 ;

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

R 4 represents H or, in the cases wherein n is not 0 and R 5 is H, may also represent OH;

R 5 represents H, (C 1 -C 3 )alkyl, (C 1 -C 3 )hydroxyalkyl, (C 1 -C 3 )aminoalkyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkyl, carboxy or (C 1 -C 3 )alkoxycarbonyl;

R 6 represents (C 1 -C 3 )hydroxyalkyl, carboxy, (C 1 -C 3 )alkoxycarbonyl, or a group —(CH 2 ) q —NR 7 R 8 wherein q is 1, 2, or 3 and each of R 7 and R 8 independently represents H or (C 1 -C 3 )alkyl or R 7 and R 8 form together with a nitrogen atom bearing them a pyrrolidinyl, piperidinyl, morpholinyl or thiomorpholinyl ring;

R 9 represents (C 1 -C 3 )alkyl, 2-hydroxy-ethyl, 2-hydroxy-propyl or 3-hydroxy-propyl;

A represents —(CH 2 ) p —, —CH 2 CH 2 CH(OH)— or —COCH 2 CH(OH)—;

G represents a phenyl group which is substituted once or twice in the meta and/or para position(s) by substituents selected independently from (C 1 -C 4 )alkyl, (C 1 -C 3 )alkoxy, or a halogen,

or G is one of the formulae G 1 and G 2 below

wherein

Q is 0 or S and X is CH or N; and

Y 1 , Y 2 and Y 3 each represent CH, or

Y 1 and Y 3 each represent CH and Y 2 represents N, or

Y 1 represents N, Y 2 represents CH or N and Y 3 represents CH, or

Y 1 and Y 2 each represent CH and Y 3 represents N; and

n is 0 when A represents —CH 2 CH 2 CH(OH)— or —COCH 2 CH(OH)—, and n is 0, 1, or 2 when A represents (CH 2 ) p , p being 1, 2, 3 or 4, with the proviso that the sum of n and p is then 2, 3, or 4;

or a salt of such a compound.

2. The compound according to claim 1 ,

wherein

R 1 represents cyano or (C 1 -C 3 )alkyl;

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

R 5 represents H, (C 1 -C 3 )alkyl, (C 1 -C 3 )hydroxyalkyl, (C 1 -C 3 )alkoxy(C 1 -C 3 )alkyl or (C 1 -C 3 )alkoxycarbonyl;

or a salt thereof of such a compound.

3. The compound according to claim 1 ,

wherein

“-----” is a bond,

V represents CH and U represents CH or N, or

V represents CR 6 and U represents CH, or

V represents N and U represents CH; or

“-----” is absent,

V represents CH and U represents CH 2 , NH or NR 9 ;

R 2 represents H, acetyl or a group of the formula —CH 2 —R 3 ;

R 6 represents (C 1 -C 3 )hydroxyalkyl, carboxy, (C 1 -C 3 )alkoxycarbonyl or a group —(CH 2 ) q —NR 7 R 8 wherein q is 1, 2 or 3 and each of R 7 and R 8 independently represents H or (C 1 -C 3 )alkyl or R 7 and R 8 form together with the nitrogen atom bearing them a pyrrolidinyl or piperidinyl ring; and

each of Y 1 and Y 3 represents CH, or one of Y 1 and Y 3 represents N and the other represents CH;

or a salt thereof.

4. The compound according to claim 1 , wherein R 1 represents (C 1 -C 3 )alkyl;

or a salt thereof.

5. The compound according to claim 1 , wherein V represents CH;

or a salt thereof.

6. The compound according to claim 1 , wherein V represents N;

or a salt thereof.

7. The compound according to claim 1 , wherein “-----” is a bond and U represents CH or N;

or a salt thereof.

8. The compound according to claim 1 , wherein “-----” is absent and U represents CH 2 , NH or NR 9 ;

or a salt thereof.

9. The compound according to claim 1 , wherein G is a group of the formula

wherein Q represents 0 or S;

or a salt thereof.

10. The compound according to claim 1 , wherein said compound is:

4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;

4-oxo-1-{3-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-oxazolidin-5-yl]-propylamino}-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-9-carbonitrile;

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

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

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

or a salt thereof.

11. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.

12. A method of treating a bacterial infection in a subject comprising administering to said subject a pharmaceutically active amount of the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

13. The compound according to claim 1 , wherein R 1 represents ethynyl;

or a salt thereof.