2-hydroxyethyl-1H-quinolin-2-one derivatives and their azaisosteric analogues with antibacterial activity
View Patent ↗The invention relates to antibacterial compounds of formula I wherein R 1 represents alkoxy; each of U and V represents CH and W represents CH or N, or U represents N, V represents CH and W represents N, or each of U and V represents N and W represents CH; R 2 represents hydrogen or fluorine when W represents CH or R 2 represents hydrogen when W represents N; A represents O or CH 2 ; Y represents CH or N; Q represents O or S; and n represents 0 or 1; and salts of such compounds.
1. A compound of formula I
wherein
R 1 represents alkoxy;
each of U and V represents CH and W represents CH, or
U represents N, V represents CH and W represents CH, or
each of U and V represents N and W represents CH;
R 2 represents hydrogen or fluorine;
A represents O or CH 2 ;
Y represents CH or N;
Q represents O or S; and
n represents 0 or 1;
or a salt of the compound.
2. The compound according to claim 1 , which is also a compound of formula I p
wherein
R 1 represents alkoxy;
U represents CH or N and W represents CH;
A represents O or CH 2 ;
Y represents CH or N; and
Q represents O or S;
or a salt of the compound.
3. The compound according to claim 1 , wherein Y represents CH;
or a salt of the compound.
4. The compound according to claim 1 , wherein Q represents O;
or a salt of the compound.
5. The compound according to claim 1 , wherein R 1 represents methoxy; or a salt of the compound.
6. The compound according to claim 1 , wherein A represents O; or a salt of the compound.
7. The compound according to claim 1 , wherein A represents CH 2 ;
or a salt of the compound.
8. The compound according to claim 1 , wherein n represents 1; or a salt of the compound.
9. The compound according to claim 1 , wherein:
R 1 represents methoxy;
U represents N and V represents N and W represents CH;
R 2 represents hydrogen;
A represents O or CH 2 ;
Y represents CH;
Q represents O or S; and
n represents 1;
or a salt of the compound.
10. The compound according to claim 1 , which is selected from:
1-((S)-2-{(2S,5R)-5-[(2,3-dihydro-4-oxa-1-thia-6-aza-naphthalen-7-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-2-hydroxy-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one;
1-((2S)-2-{(2S,5R)-5-[(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-2-hydroxy-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one;
1-((2S)-2-{(2S,5R)-5-[(6,7-dihydro-[1,4]dioxino[2,3-c]pyridazin-3-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-2-hydroxy-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one;
1-(2R)-2-{4-[(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-amino]-cyclohexyl}-2-hydroxy-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one;
1-((2S)-2-{(2S,5R)-5-[(6,7-dihydro-8-oxa-5-thia-1,2-diaza-naphthalen-3-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-2-hydroxy-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one;
1-(2S)-2-hydroxy-2-{(2S,5R)-5-[(3-oxa-1-thia-5-aza-indan-6-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one
3-fluoro-1-((2S)-2-hydroxy-2-{(2S,5R)-5-[(3-oxa-1-thia-5-aza-indan-6-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-ethyl)-7-methoxy-1H-[1,8]naphthyridin-2-one;
5-((2S)-2-{(2S,5R)-5-[(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-amino]-tetrahydro-pyran-2-yl}2-hydroxy-ethyl)-3-methoxy-5H-pyrido[2,3-b]pyrazin-6-one;
5-(2S)-2-{(2S,5R)-5-[(2,3-dihydro-4-oxa-1-thia-6-aza-naphthalen-7-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-2-hydroxy-ethyl)-3-methoxy-5H-pyrido[2,3-b]pyrazin-6-one; or
5-((S)-2-{(2S,5R)-5-[(6,7-dihydro-8-oxa-5-thia-1,2-diaza-naphthalen-3-ylmethyl)-amino]-tetrahydro-pyran-2-yl}-2-hydroxy-ethyl)-3-methox y-5H-pyrido [2,3-b]pyrazin-6-one;
or a salt of the compound.
11. A medicament comprising the compound according to claim 1 , or a pharmaceutically acceptable salt thereof.
12. A pharmaceutical composition comprising as an active principal, the compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and at least one therapeutically inert excipient.