Depsipeptide and uses thereof

• US 9,163,065 B2
• Filed: 12/03/2013
• Issued: 10/20/2015
• Est. Priority Date: 12/03/2012
• Status: Active Grant

• Current Assignee: NovoBiotic Pharmaceuticals, LLC
• Original Assignee: NovoBiotic Pharmaceuticals, LLC
• Inventors: Peoples, Aaron J., Hughes, Dallas, Ling, Losee Lucy, Millett, William, Nitti, Anthony, Spoering, Amy, Steadman, Victoria Alexandra, Chiva, Jean-Yves Christophe, Lazarides, Linos, Jones, Michael Kenyon, Lewis, Kim, Epstein, Slava, Poullennec, Karine Gaelle
• Primary Examiner(s): HEARD, THOMAS SWEENEY
• Application Number:
  US14/095,415
• Publication Number:
  US 20140194345A1
• Time in Patent Office: 686 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/15 Depsipeptides; Derivatives thereof
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/04 Amoebicides
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: A61P 33/10 Anthelmintics
• CPC Class Codes: A61P 33/12 Schistosomicides
• CPC Class Codes: C07K 11/02 cyclic, e.g. valinomycins ; Derivatives thereof
• CPC Class Codes: C07K 7/56 the cyclisation not occurring through 2,4-diamino-butanoic acid
• CPC Class Codes: C12N 1/205 Bacterial isolates
• CPC Class Codes: C12P 17/14 Nitrogen or oxygen as hetero atom and at least one other diverse hetero ring atom in the same ring
• CPC Class Codes: C12P 21/02 : having a known sequence of two or more amino acids, e.g. glutathione
• CPC Class Codes: C12R 2001/01 : Bacteria or Actinomycetales ; using bacteria or Actinomycetales
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates generally to novel depsipeptides, to methods for the preparation of these novel depsipeptides, to pharmaceutical compositions comprising the novel depsipeptides; and to methods of using the novel depsipeptides to treat or inhibit various disorders.

Claims

1. A method of treating a bacterial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (II):

2. The method of claim 1, wherein the bacterial infection is caused by a Gram-positive bacterium.

3. The method of claim 2, wherein the Gram-positive bacterium is selected from the group consisting of Streptococcus, Staphylococcus, Enterococcus, Corynebacteria, Listeria, Bacillus, Erysipelothrix, Mycobacterium, Clostridium, Propionibacterium, and Actinomycetales.

4. The method of claim 2, wherein the Gram-positive bacterium is selected from the group consisting of methicillin-susceptible and methicillin-resistant staphylococci (including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, and coagulase-negative staphylococci), glycopeptide intermediate-susceptible Staphylococcus aureus (GISA), penicillin-susceptible and penicillin-resistant streptococci (including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus avium, Streptococcus bovis, Streptococcus lactis, Streptococcus sangius, Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus and Streptococci Group C, Streptococci Group G and Viridans streptococci), enterococci (including vancomycin-susceptible and vancomycin-resistant strains such as Enterococcus faecalis and Enterococcus faecium), Clostridium difficile, Clostridium clostridiiforme, Clostridium innocuum, Clostridium perfringens, Clostridium tetani, Propionibacterium acnes, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium kansaii, Mycobacterium gordonae, Mycobacteria sporozoites, Listeria monocytogenes, Bacillus subtilis, Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Corynebacterium sporozoites, Erysipelothrix rhusiopathiae, and Actinomyces israelli.

5. The method of claim 2, wherein the bacterial infection is caused by Bacillus anthracis.

6. The method of claim 1, wherein the bacterial infection is caused by a Gram-negative bacterium.

7. The method of claim 6, wherein the Gram-negative bacterium is selected from the group consisting of Haemophilus influenzae, Moraxella catarrhalis, and Escherichia coli.

8. The method of claim 1, wherein said effective amount of the compound is 1 μ

g/kg-100 mg/kg.

9. The method of claim 1, wherein said effective amount of the compound is 1 μ

g/kg-50 mg/kg.

10. The method of claim 1, wherein said effective amount of the compound is 10 μ

g/kg-10 mg/kg.

11. The method of claim 1, wherein said compound is administered via a route selected from the group consisting of oral, parenteral, transdermal, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, intraocular, intraaural, colorectal, rectal, intravaginal, and any combinations thereof.

12. The method of claim 1, wherein said compound is administered daily, weekly, monthly or yearly.

13. The method of claim 1, wherein said composition is administered daily for about a week, two weeks, three weeks, one month, three months, six months or a year.

14. The method of claim 1, wherein said subject is a human.

15. A method of treating a bacterial infection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (III):

16. The method of claim 15, wherein the bacterial infection is caused by a Gram-positive bacterium.

17. The method of claim 16, wherein the Gram-positive bacterium is selected from the group consisting of Streptococcus, Staphylococcus, Enterococcus, Corynebacteria, Listeria, Bacillus, Erysipelothrix, Mycobacterium, Clostridium, Propionibacterium, and Actinomycetales.

18. The method of claim 16, wherein the Gram-positive bacterium is selected from the group consisting of methicillin-susceptible and methicillin-resistant staphylococci (including Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, and coagulase-negative staphylococci), glycopeptide intermediate-susceptible Staphylococcus aureus (GISA), penicillin-susceptible and penicillin-resistant streptococci (including Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus avium, Streptococcus bovis, Streptococcus lactis, Streptococcus sangius, Streptococcus anginosus, Streptococcus intermedius, Streptococcus constellatus and Streptococci Group C, Streptococci Group G and Viridans streptococci), enterococci (including vancomycin-susceptible and vancomycin-resistant strains such as Enterococcus faecalis and Enterococcus faecium), Clostridium difficile, Clostridium clostridiiforme, Clostridium innocuum, Clostridium perfringens, Clostridium tetani, Propionibacterium acnes, Mycobacterium tuberculosis, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium kansaii, Mycobacterium gordonae, Mycobacteria sporozoites, Listeria monocytogenes, Bacillus subtilis, Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Corynebacterium sporozoites, Erysipelothrix rhusiopathiae, and Actinomyces israelli.

19. The method of claim 16, wherein the bacterial infection is caused by Bacillus anthracis.

20. The method of claim 15, wherein the bacterial infection is caused by a Gram-negative bacterium.

21. The method of claim 20, wherein the Gram-negative bacterium is selected from the group consisting of Haemophilus influenzae, Moraxella catarrhalis, and Escherichia coli.

22. The method of claim 15, wherein said effective amount of the compound is 1 μ

g/kg-100 mg/kg.

23. The method of claim 15, wherein said effective amount of the compound is 1 μ

g/kg-50 mg/kg.

24. The method of claim 15, wherein said effective amount of the compound is 10 μ

g/kg-10 mg/kg.

25. The method of claim 15, wherein said compound is administered via a route selected from the group consisting of oral, parenteral, transdermal, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, intraocular, intraaural, colorectal, rectal, intravaginal, and any combinations thereof.

26. The method of claim 15, wherein said compound is administered daily, weekly, monthly or yearly.

27. The method of claim 15, wherein said composition is administered daily for about a week, two weeks, three weeks, one month, three months, six months or a year.

28. The method of claim 15, wherein said subject is a human.