Antibacterial oxadiazolone derivatives

Patent metadata

Field	Value
Publication number	US-9487516-B2
Application number	US-201414760096-A
Country	US
Kind code	B2
Filing date	Jan 8, 2014
Priority date	Jan 9, 2013
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

The invention relates to antibacterial compounds of formula I

wherein
U represents CH or N; V represents CH or N, provided that at least one of U and V does not represent N; R represents H, halogen, methyl, methoxy, cyano or ethynyl; either W represents a phenyl group substituted in para position with (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy or (C 1 -C 3 )thioalkoxy and optionally in meta position with halogen, or W is a group having one of the formulae W 1 and W 2 below

wherein
Q is O or S and X is CH or N;

and salts of such compounds.

First claim

The invention claimed is:

1. A compound of formula I

wherein
U represents CH or N;
V represents CH or N, provided that at least one of U and V does not represent N;
R represents H, halogen, methyl, methoxy, cyano or ethynyl;
either W represents a phenyl group substituted in para position with (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy or (C 1 -C 3 )thioalkoxy and optionally in meta position with halogen, or W is a group having one of the formula W 1 or W 2 below;

wherein
Q is O or S and
X is CH or N;
or a salt thereof.

2. The compound according to claim 1 , wherein
V represents CH and
R represents fluorine;
or a salt thereof.

3. The compound according to claim 1 , wherein U represents CH; or a salt thereof.

4. The compound according to claim 3 , wherein W is a group of formula W 1
or a salt thereof.

5. The compound according to claim 1 , wherein U represents N; or a salt thereof.

6. The compound according to claim 5 , wherein W is a group of formula W 1
or a salt thereof.

7. The compound according to claim 1 , wherein W represents a phenyl group substituted in para position with (C 2 -C 3 )alkyl, (C 1 -C 2 )alkoxy or (C 1 -C 2 )thioalkoxy and optionally in meta position with fluorine;
or a salt thereof.

8. The compound according to claim 1 , wherein W is a group of formula W 1
or a salt thereof.

9. The compound according to claim 1 , wherein W is a group of formula W 2
or a salt thereof.

10. The compound according to claim 1 , wherein
R represents H, fluorine or cyano; and
either W represents a phenyl group substituted in para position with (C 2 -C 3 )alkyl, (C 1 -C 2 )thioalkoxy or (C 1 -C 2 )alkoxy and optionally in meta position with fluorine, or W is a group having one of the formula W 1 or W 2
or a salt thereof.

11. The compound according to claim 1 , wherein said compound is:
(S)-9-fluoro-1-{3-[5-oxo-4-(4-propyl-phenyl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-7-fluoro-6-{3-[5-oxo-4-(4-propyl-phenyl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-9-fluoro-1-{3-[4-(4-isopropyl-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-1-{3-[4-(4-ethylsulfanyl-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-6-{3-[4-(4-ethylsulfanyl-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-9-fluoro-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-7-fluoro-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-1-{3-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-1-{3-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-6-{3-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-6-{3-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-9-fluoro-1-{3-[5-oxo-4-(4-propyl-phenyl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-7-fluoro-6-{3-[5-oxo-4-(4-propyl-phenyl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-1-{3-[4-(4-ethoxy-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(R)-1-{3-[4-(4-ethoxy-phenyl)-5-oxo-4,5-dihydro[1,3,4]oxadiazol-2-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
(S)-6-{3-[4-(4-ethoxy-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-6-{3-[4-(4-ethoxy-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-1-{3-[4-(4-ethylsulfanyl-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-9-fluoro-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
{3-[4-(4-ethylsulfanyl-phenyl)-5-oxo-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-7-fluoro-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(S)-1-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-1,2-dihydro-pyrrolo[3,2,1-ij]quinolin-4-one;
{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)-4,5-dihydro-[1,3,4]oxadiazol-2-yl]-propylamino}-5,6-dihydro-pyrrolo[1,2,3-de]quinoxalin-3-one;
(R)-6-{3-[5-oxo-4-(3-oxo-3,4-dihydro-2H-pyrido[3

Assignees

• Actelion Pharmaceuticals Ltd
• Actelion Pharmaceuticals Ltd

Inventors

• Hubschwerlen Christian
• Rueedi Georg
• Zumbrunn Cornelia

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P31/06

  for tuberculosis · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P27/16

  Otologicals · CPC title