Antibacterial and antiparasitic quinoxaline-2,3-diamine derivatives

Patent metadata

Field	Value
Publication number	US-12503448-B2
Application number	US-202017620670-A
Country	US
Kind code	B2
Filing date	Jul 3, 2020
Priority date	Jul 4, 2019
Publication date	Dec 23, 2025
Grant date	Dec 23, 2025

Abstract

A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a patient infected with pathogenic organisms; wherein X and Y are each independently selected from C, N, O and S, provided at least one of X and Y is N, O or S; wherein R 1 and R 2 are each independently selected from an optionally substituted C 1 -C 8 alkyl, C 1 -C 8 alkenyl, aryl, heteroaryl or alkylaryl group; and wherein Z is selected from H, —CN, —NO 2 , —NR 3 R 4 , —NR 5 (CO)R 6 ; C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —(CO)WR 12 , hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups. The compounds may be effective in treating patients/animals infected with parasites selected from Schistosoma, Haemonchus, Eimeria, Echinococcus, Dirofilaria, Fasciola or Plasmodium parasites. Additionally or alternatively, the compounds of formula (I) may be effective in treating patients infected with pathogenic bacteria selected from S. aureus , MRSA and Enterococcus faecalis.

First claim

The invention claimed is:

1 . A method of treating a patient infected with parasites selected from schistosome, Fasciola , or Plasmodium parasites and/or a patient infected pathogenic bacteria selected from S. aureus , MRSA and Enterococcus faecalis , the method comprising administering to said patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof;

wherein X and Y are each N;
wherein R 1 and R 2 are each independently selected from a C 1 -C 8 alkyl, a C 1 -C 8 alkenyl, an aryl group, or an alkylaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups; or a (CO)OR 13 or (CO)NHR 13 group wherein R 13 is selected from said groups;
wherein Z is selected from —NO 2 , —NR 3 R 4 , or —NR 5 (CO)R 6 ;
wherein R 3 and R 4 are each independently selected from H, a C 1 -C 6 alkyl, optionally forming a ring, a C 1 -C 6 alkenyl, an aryl group, or a heteroaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups; or a (CO)OR 14 or (CO)NHR 14 group wherein R 14 is selected from said groups;
wherein R 5 is selected from H, a C 1 -C 6 alkyl or a C 1 -C 6 alkenyl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups;
wherein R 6 is selected from a C 1 -C 6 alkyl, a C 1 -C 6 alkenyl, an aryl or a heteroaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups; or a (CO)OR 15 or (CO)NHR 15 group wherein R 15 is selected from said groups;
wherein R 7 and R 8 , when present, are each independently selected from a H or a C 1 -C 4 alkyl;
wherein R 9 , R 10 and R 11 are each independently selected from H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —(CO)WR 12 , hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups;
wherein W is a bond, N or O and wherein R 12 is selected from C 1 -C 6 alkyl, a C 1 -C 6 alkenyl, an aryl or a heteroaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups.

2 . The method according to claim 1 , wherein R 1 and R 2 are each independently selected from an aryl group or an alkylaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, OH, NH 2 , SH, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups.

3 . The method according to claim 1 , wherein the groups R 1 and R 2 are the same.

4 . The method according to claim 1 , wherein R 7 and R 8 are both H.

5 . The method according to claim 1 , wherein Z is —NR 3 R 4 or —NR 5 (CO)R 6 .

6 . The method according to claim 5 , wherein Z is —NR 3 R 4 and wherein R 3 and R 4 are independently selected from H, a C 1 -C 6 alkyl, optionally forming a ring, optionally substituted with one or more of C 1 -C 2 alkoxy, F, Cl and CF 3 groups.

7 . The method according to claim 5 , wherein Z is NR 5 (CO)R 6 , wherein R 5 is H or methyl; wherein R 6 is selected from a C 1 -C 6 alkyl, or an aryl group, optionally substituted with one or more of C 1 -C 2 alkyl, C 1 -C 2 alkoxy, F, Cl or CF 3 groups.

8 . The method according to claim 1 , wherein the pathogenic organisms which the patient is infected with are parasites selected from schistosome, Fasciola or Plasmodium parasites.

9 . The method according to claim 1 , wherein the pathogenic organisms which the patient is infected with are pathogenic bacteria selected from S. aureus , MRSA and Enterococcus faecalis.

10 . A method of treating a patient infected with parasites selected from schistosome, Fasciola , or Plasmodium parasites and/or a patient infected pathogenic bacteria selected from S. aureus , MRSA and Enterococcus faecalis , the method comprising administering to said patient a therapeutically effective amount of a compound of formula (III), or a pharmaceutically acceptable salt or solvate thereof;

wherein R 1 and R 2 are independently selected from a C 1 -C 8 alkyl, a C 1 -C 8 alkenyl, an aryl group or an alkylaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, fluoro, chloro, CF 3 , CHF 2 or CH 2 F groups;
wherein Z is selected from —NR 3 R 4 or —NR 5 (CO) R 6 ;
wherein R 3 and R 4 are each independently selected from H, a C 1 -C 6 alkyl, optionally forming a ring, a C 1 -C 6 alkenyl, an aryl group, or a heteroaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups;
wherein R 5 is selected from H, a C 1 -C 6 alkyl or a C 1 -C 6 alkenyl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups;
wherein R 6 is selected from a C 1 -C 6 alkyl, a C 1 -C 6 alkenyl, an aryl or a heteroaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups;
wherein R 7 and R 8 are each independently selected from a H or a C 1 -C 4 alkyl;
wherein R 9 , R 10 and R 11 are each independently selected from H, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —(CO)WR 12 , hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups;
wherein W is a bond, N or O and wherein R 12 is selected from C 1 -C 6 alkyl, a C 1 -C 6 alkenyl, an aryl or a heteroaryl group, optionally substituted with one or more of C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylamino, C 1 -C 4 alkylthio, hydroxy, amino, thiol, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups.

11 . The method according to claim 10 , wherein R 1 and R 2 are independently selected from an aryl group or an alkylaryl group, optionally substituted with one or more of C 1 -C 4 alkoxy, chloro, fluoro, CF 3 , CHF 2 or CH 2 F groups.

12 . The method according to claim 10 , wherein the compound is a medicament.

13 . A method for disinfecting parasites selected from schistosome, Fasciola , or Plasmodium parasites and/or a patient infected pathogenic bacteria selected from S. aureus , MRSA and Enterococcus faecalis from a surface, the method comprising the step of applying, to a surface, a compound according to of formula (I), or a pharmaceutically acceptable salt or solvate thereof;

wherein X and Y are each N;
wherein R 1 and R 2 are each independently selected from a C 1 -C 8 alkyl, a C 1 -C 8 alkenyl, an aryl group, an alkylaryl g

Assignees

• Univ College Cardiff Consultants Ltd
• Aberystwyth Univ

Inventors

• Brancale Andrea
• Padalino Gilda
• Hoffman Karl

Classifications

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D339/08

  Six-membered rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61P33/12

  Schistosomicides · CPC title

• A61P31/04

  Antibacterial agents · CPC title