Fluoroquinolones and use thereof to treat bacterial infections

Patent metadata

Field	Value
Publication number	US-10087165-B2
Application number	US-201515319620-A
Country	US
Kind code	B2
Filing date	Jun 18, 2015
Priority date	Jun 18, 2014
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.

First claim

The invention claimed is:

1. A compound of general Formula I:

and pharmaceutically acceptable salts thereof, wherein:
R 1 represents a saturated or unsaturated, substituted or unsubstituted, branched or unbranched alkyl group comprising 4 to 20 carbons atoms, when the alkyl group is substituted, the substituent is selected in the group comprising halo, hydroxyl, nitro, amido, carboxy, amino, cyano, alkoxy, haloalkoxy, or haloalkyl,
R 2 represents a substituent selected from the group comprising hydrogen, alkyl, alkene, alkyne, cycloalkyl, aryl, halo, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, alkoxy, haloalkoxy, or haloalkyl,
R 3 , R 4 , R 5 and R 6 may be identical or different and each represents a substituent selected from hydrogen, alkyl, alkene, alkyne, cycloalkyl, aryl, halo, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, alkoxy, haloalkoxy, or haloalkyl,
R 7 represents a substituent selected from hydrogen, alkyl, alkene, alkyne, cycloalkyl, aryl, halo, hydroxyl, oxo, nitro, amido, carboxy, amino, cyano, alkoxy, haloalkoxy, or haloalkyl,

with the condition that the compounds of formula I are not:
7-(4-butylpiperazin-l-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-heptylpiperazin-l-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
7-(4-butyl-3-methylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-hexyl-3-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-(4-hydroxybuty)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,

with the condition that when R 2 is a hydrogen and R 7 is a fluorine, R 3 , R 4 , R 5 and R 6 are not a methyl group.

2. The compound according to claim 1 , wherein R 1 represents a saturated or unsaturated, substituted or unsubstituted, branched or unbranched alkyl group comprising 5 to 16 carbons atoms.

3. The compound according to claim 1 , wherein R 2 represents a substituent selected from the group comprising hydrogen, methyl, methoxy, ethoxy, chloro and fluoro.

4. The compound according to claim 1 , wherein R 3 , R 4 , R 5 and R 6 are identical and represent each a hydrogen.

5. The compound according to claim 1 , wherein R 7 representsa hydrogen, NH 2 or fluoro.

6. The compound according to claim 1 , having the general formula II corresponding to the general formula I wherein R 7 is a fluorine:

and pharmaceutically acceptable salts thereof.

7. The compound according to claim 1 , having the general formula III corresponding to compounds of general formula II wherein R 3 , R 4 , R 5 and R 6 are identical and represent a hydrogen atom:

and pharmaceutically acceptable salts thereof.

8. The compound according to claim 1 , selected from the group comprising:
1-cyclopropyl-6-fluoro-4-oxo-7-(4-pentylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-hexylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-octylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-nonylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-7-(4-decylpiperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-4-oxo-7-(4-undecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-7-(4-dodecylpiperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-4-oxo-7-(4-tridecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-4-oxo-7-(4-tetradecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-4-oxo-7-(4-pentadecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-hexadecylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(4-pentylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-hexylpiperazin-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-heptylpiperazin-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-7-(4-octylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-7-(4-nonylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-7-(4-decylpiperazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(4-undecylpiperazin-1- yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-7-(4-dodecylpiperazin-1-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(4-tridecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(4-tetradecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-7-(4-pentadecylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid,
1-cyclopropyl-6-fluoro-7-(4-hexadecylpiperazin-1-yl)-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid,

and pharmaceutically acceptable salts thereof.

9. A pharmaceutical composition comprising at least one compound according to claim 1 , or a pharmaceutically acceptable salt, and at least one pharmaceutically acceptable carrier, diluent, excipient and /or adjuvant.

10. The pharmaceutical composition according to claim 9 , further comprising a therapeutic agent and/or active ingredient.

11. A medicament comprising a compound according to claim 1 .

12. The medicament according to claim 11 , further comprising a therapeutic agent and/or active ingredient.

Assignees

• Univ Pierre Et Marie Curie—Paris 6 Upmc
• Univ Sorbonne

Inventors

• Aubry Alexandra
• Anquetin Guillaume

Classifications

• C07D401/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title