Oxazolidinyl antibiotics
View Patent ↗The invention relates to antibacterial compounds of formula I wherein R 1 is alkoxy or halogen; U and V each independently are CH or N; is a bond or is absent; W is CH or N or, when is absent, W is CH 2 or NH, with the proviso that U, V and W are not all N; A is a bond or CH 2 ; R 2 is H or, provided A is CH 2 , may also be OH; m and n each independently are 0 or 1; D is CH 2 or a bond; G represents a phenyl group substituted once or twice in the meta and/or para position(s) by substituents selected from alkyl, (C 1 -C 3 )alkoxy and halogen, or G is a group G 1 or G 2 wherein Z 1 , Z 2 and Z 3 may each represent CH or N; X is N or CH and Q is O or S; it being understood that if m and n each are 0, then A is CH 2 ; and salts of such compounds.
1. A compound of formula I
wherein
R 1 represents alkoxy or halogen;
U and V each independently represent CH or N;
is a bond or is absent;
W represents CH or N, or when is absent, W represents CH 2 or NH, with the proviso that U, V and W do not all represent N;
A represents a bond or CH 2 ;
R 2 represents H, or provided A is CH 2 , may also represent OH;
m and n each independently represent 0 or 1;
D represents CH 2 or a bond;
G represents a phenyl group substituted once or twice in the meta and/or para position(s) by substituents selected from alkyl, (C 1 -C 3 )alkoxy, or halogen, or
G is one of the groups G 1 and G 2
wherein
Z 1 , Z 2 , and Z 3 each represent CH, or Z 1 and Z 2 each represent CH, and Z 3 represents N, or Z 1 represents CH, Z 2 represents N, and Z 3 represents CH or N, or Z 1 represents N, and Z 2 and Z 3 each represent CH; and X represents N or CH and Q represents O or S; it being understood that if m and n each represent 0, then A represents CH 2 ;
or a salt thereof.
2. The compound according to claim 1 , wherein
R 1 represents alkoxy;
V represents CH;
U and W each represent CH and is a bond, or U represents CH, W represents N and is a bond, or U and W each represent N and is a bond, or U represents CH, W represents CH 2 and is absent;
A represents a bond or CH 2 ;
R 2 represents H, or provided A is CH 2 , may also represent OH;
m and n each independently represent 0 or 1;
D represents CH 2 or a bond;
G represents an phenyl group which is substituted once in a meta and once in the para position by substituents selected from alkyl or halogen, or G is one of the groups G 1 , and G 2 ,
wherein Q represents O or S;
it being understood that if m and n each represent 0, then A represents CH 2 ;
or a salt thereof.
3. The compound according to claim 1 , wherein R 1 is methoxy; or a salt thereof.
4. The compound according to claim 1 , wherein is a bond; or a salt thereof.
5. The compound according to claim 1 , wherein is absent; or a salt thereof.
6. The compound according to claim 1 , wherein A represents a bond; or a salt thereof.
7. The compound according to claim 1 , wherein A represents CH 2 ; or a salt thereof.
8. The compound according to claim 7 , wherein R 2 represents OH; or a salt thereof.
9. The compound according to claim 1 , wherein G is a group of the formula
wherein Q represents O or S;
or a salt thereof.
10. The compound according to claim 1 , which is:
6-{(R)-5-[3-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
1-{1-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-azetidin-3-ylmethyl}-7-methoxy-1H-quinolin-2-one;
6-{(R)-5-[3-(7-methoxy-2-oxo-2H-quinoxalin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{2-[3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-azetidin-1-yl]-ethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{2-[3-(7-methoxy-2-oxo-2H-quinoxalin-1-ylmethyl)-azetidin-1-yl]-ethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[4-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-piperidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
1-{1-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-piperidin-4-ylmethyl}-7-methoxy-1H-quinolin-2-one;
1-{1-[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-piperidin-4-ylmethyl}-7-methoxy-1H-quinolin-2-one;
6-{(R)-5-[3-(7-methoxy-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(S)-5-[3-(7-methoxy-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[3-(7-methoxy-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;
6-{(R)-5-[3-(7-methoxy-2-oxo-2H-quinoxalin-1-ylmethyl)-azetidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]oxazin-3-one;
1-{1-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-azetidin-3-ylmethyl}-7-methoxy-1H-quinoxalin-2-one;
6-methoxy-4-{1-[(R)-2-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-oxazolidin-5-ylmethyl]-piperidin-4-yl}-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]oxazin-6-yl)-oxazolidin-5-ylmethyl]-piperidin-4-yl}-4H-pyrido[2,3-b]pyrazin-3-one;
6-{(R)-5-[(R)-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(R)-5-[3-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-{(S)-5-[3-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-pyrrolidin-1-ylmethyl]-2-oxo-oxazolidin-3-yl}-4H-benzo[1,4]thiazin-3-one;
6-((S)-5-{2-[3-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-pyrrolidin-1-yl]-ethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;
6-((R)-5-{2-[3-hydroxy-3-(7-methoxy-2-oxo-2H-quinolin-1-ylmethyl)-pyrrolidin-1-yl]-ethyl}-2-oxo-oxazolidin-3-yl)-4H-benzo[1,4]thiazin-3-one;
4-{1-[(R)-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2-oxo-oxazolidin-5-ylmethyl]-piperidin-4-yl}-6-methoxy-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}-piperidin-4-yl)-4H-pyrido[2,3-b]pyrazin-3-one;
4-{1-[(R)-3-(3-fluoro-4-methyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-piperidin-4-yl}-6-methoxy-4H-pyrido[2,3-b]pyrazin-3-one; or
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}-piperidin-4-yl)-4H-pyrido[2,3-b]pyrazin-3-one;
or a salt thereof.
11. A medicament comprising; a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
12. 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.
13. A method of treating a bacterial infection in a patient comprising administering to the patient in need thereof, a therapeutically effective amount of the compound according to claim 11 .
14. A method of treating a bacterial infection in a patient comprising administering to the patient in need thereof, a therapeutically effective amount of the composition according to claim 12 .
15. The compound according to claim 1 , wherein A represents a bond and m and n each represent 1; or a salt thereof.
16. The compound according to claim 1 , wherein A represents CH 2 and one of m and n represents 0 and the other represents 1; or a salt thereof.
17. The compound according to claim 1 , wherein A represents CH 2 and m and n each represent 1; or a salt thereof.