Antibacterial agents

Patent metadata

Field	Value
Publication number	US-10759740-B2
Application number	US-201716086927-A
Country	US
Kind code	B2
Filing date	Mar 24, 2017
Priority date	Mar 24, 2016
Publication date	Sep 1, 2020
Grant date	Sep 1, 2020

Abstract

The invention provides an antibacterial compound of formula (I) or a salt thereof, as well as an antibacterial compound of formula (II) or a salt thereof, wherein R 1 , R 2 , W, X, Y and n have any of the values defined in the specification.

First claim

What is claimed is:

1. A compound of formula I:

wherein:
R 1 is a polyether or a (C 1 -C 6 )alkyl that is substituted with one or more NR a R b ;
R 2 is a polyether or a (C 1 -C 6 )alkyl that is substituted with one or more NR a R b ;
each W is independently —NH—, —O— or —S—;
each X is independently (C 4 -C 14 )alkyl;
each R a is independently H or (C 1 -C 6 )alkyl;
each R b is independently H, (C 1 -C 6 )alkyl or —C(═NH)NH 2 ; and
n is 1, 2, 3, 4, 5, 6, 7, or 8;
or a salt thereof.

2. A compound of formula II:

wherein:
R 1 is a polyether or a (C 1 -C 6 )alkyl that is optionally substituted with one or more NR a R b ;
R 2 is a polyether or a (C 1 -C 6 )alkyl that is optionally substituted with one or more NR a R b ;
each W is independently —NH—, —O— or —S—;
each X is independently (C 2 -C 20 )alkyl;
R a and R b are each independently H or (C 1 -C 6 )alkyl;
each Y is independently —NH 2 , —N + (R c ) 3 Z − , —NH—C(═NH)—NH 2 or NH—BOC;
each R c is independently (C 1 -C 6 )alkyl;
Z − is a counter ion; and
n is 1, 2, 3, 4, 5, 6, 7, or 8;
or a salt thereof.

3. The compound or salt of claim 1 , wherein R 1 is (C 1 -C 6 )alkyl substituted with one or more NR a R b .

4. The compound or salt of claim 3 wherein R 1 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or sec-butyl, substituted with one or more NR a R b .

5. The compound or salt of claim 1 , wherein R 2 is a (C 1 -C 6 )alkyl that is substituted with one or more NR a R b .

6. The compound or salt of claim 5 wherein R 2 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or sec-butyl, substituted with one or more NR a R b .

7. The compound or salt of claim 1 , wherein each X is independently (C 4 -C 12 )alkyl.

8. The compound or salt of claim 1 , wherein each X is independently (C 10 )alkyl.

9. The compound or salt of claim 1 , wherein each X is independently (C 12 )alkyl.

10. The compound or salt of claim 1 , wherein each W is independently —NH—.

11. The compound or salt of claim 1 , wherein n is 2.

12. The compound or salt of claim 1 which is a compound of formula (Id):

or a salt thereof.

13. The compound or salt of claim 1 which is selected from the group consisting of:

and salts thereof.

14. The salt of claim 1 which is selected from the group consisting of:

15. A pharmaceutical composition comprising a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

16. A method for treating a bacterial infection in a mammal comprising administering to the mammal an effective amount of a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof.

17. The method of claim 16 , wherein the bacterial infection is caused by a bacterial strain selected from the group consisting of Escherichia coli, Caulobacter crescentus, Pseudomonas aeruginosa, Agrobacterium tumefaciens, Branhamella catarrhalis, Citrobacter diversus, Enterobacter aerogenes, Enterobacter cloacae, Enterobacter sakazakii, Enterobacter asburiae, Pantoea agglomerans, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella rhinoscleromatis, Proteus mirabilis, Salmonella typhimurium, Salmonella enteriditis, Serratia marcescens, Shigella sonnei, Neisseria gonorrhoeae, Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter lwoffi, Salmonella enteriditis, Fusobacterium nucleatum, Veillonella parvula, Bacteroides forsythus, Actinobacillus actinomycetemcomitans, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Helicobacter pylori, Francisella tularensis, Yersinia pestis, Borrelia burgdorferi, Neisseria meningitides, Burkholderia cepacia, Brucella neotomae, Legionella pneumophila, Y. pseudotuberculosis, Salmonella enterica serovar typhimurium, Haemophilus influenza, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, Streptococcus faecalis, Enterococcus faecalis, Enterococcus faecium, Bacillus subtilis, Micrococcus luteus, Bacillus anthracis, Bacillus cereus, Clostridium difficile, Propionibacterium acnes, Streptococcus mutans, Actinomyces viscosus, Actinomyces naeslundii, Streptococcus sanguis, Streptococcus pneumoniae, Listeria monocytogenes, Streptococcus salivarius, Gardnerella vaginalis, Peptostreptococcus anaerobius, Mobiluncus curtisii, Prevotella bivia and Mycobacterium tuberculosis.

18. The method of claim 16 , further comprising administering a second therapeutic agent, wherein the second therapeutic agent is an antibiotic agent selected from the group consisting of clindamycin, metronidazole and tinidazole.

19. The pharmaceutical composition of claim 15 , further comprising an antibiotic agent.

20. The method of claim 16 , wherein the bacterial infection is vaginosis.

21. The method of claim 16 , wherein the bacterial infection is caused by Gardnerella vaginalis, Peptostreptococcus anaerobius, Mobiluncus curtisii , and/or Prevotella bivia.

22. The compound or salt of claim 2 , wherein R 1 is a (C 1 -C 6 )alkyl that is optionally substituted with one or more NR a R b .

23. The compound or salt of claim 22 , wherein R 1 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or sec-butyl.

24. The compound or salt of claim 2 , wherein R 1 is (C 1 -C 6 )alkyl substituted with one or more NR a R b .

25. The compound or salt of claim 2 , wherein R 2 is a (C 1 -C 6 )alkyl that is optionally substituted with one or more NR a R b .

26. The compound or salt of claim 25 , wherein R 2 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or sec-butyl.

27. The compound or salt of claim 2 , wherein R 2 is a (C 1 -C 6 )alkyl that is substituted with one or more NR a R b .

28. The compound or salt of claim 2 , wherein each Y is independently —NH 2 .

29. The compound or salt of claim 2 , wherein each X is independently (C 4 -C 12 )alkyl.

30. The compound or salt of claim 2 , wherein each X is independently (C 7 )alkyl.

31. The compound or salt of claim 2 , wherein each X is independently (C 9 )alkyl.

32. The compound or salt of claim 2 , wherein each X is independently (C 11 )alkyl.

33. The compound or salt of claim 2 , wherein each W is independently —NH—.

34. The compound or salt of claim 2 , wherein n is 2.

35. The compound or salt of claim 2 , which is a compound of formula (IIc′):

wherein:
R 1 is a polyether or a (C 1 -C 6 )alkyl; and
R 2 is a polyether or a (C 1 -C 6 )alk

Assignees

• Univ Rutgers

Inventors

• Uhrich Kathryn
• Zhang Yingyue
• Faig Allison
• Chikindas Michael

Classifications

• C07C235/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• A61K31/164

  of a carboxylic acid with an aminoalcohol, e.g. ceramides · CPC title

• A61K31/7056

  containing five-membered rings with nitrogen as a ring hetero atom · CPC title

• A61K45/06

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

• A61K31/4168

  having a nitrogen attached in position 2, e.g. clonidine · CPC title