Peptoid oligomers, pharmaceutical compositions and methods of using the same

Patent metadata

Field	Value
Publication number	US-9872495-B2
Application number	US-201615093880-A
Country	US
Kind code	B2
Filing date	Apr 8, 2016
Priority date	Feb 24, 2009
Publication date	Jan 23, 2018
Grant date	Jan 23, 2018

Abstract

Novel peptoid oligomers are disclosed that have a formula represented by the following formula I:

The peptoids demonstrate antimicrobial activity and may be prepared as pharmaceutical compositions and used for the prevention or treatment of a variety of conditions in mammals including humans where microbial invasion is involved. The present cyclic and linear peptoids are particularly valuable as their effect is rapid, broad in spectrum and mostly indifferent to resistance provoked by standard antibiotics.

First claim

What is claimed is:

1. A method for treating, ameliorating or managing a disease or condition, which comprises administering to a patient in need of such treatment, amelioration or management a therapeutically acceptable amount of a peptoid oligomer according to formula Ib

a salt, stereoisomers, isotopic variants, or tautomers thereof;
wherein each R 1 is independently substituted or unsubstituted alkyl; each R 2 is independently hydrogen, or substituted or unsubstituted alkyl; or each R 1 and R 2 are joined together to form a 4-7 membered heterocyclic ring; the said peptoid oligomer consists of one or more monomers selected from Nap, Nab, Nah, Ngb, Npm, Nnm, Ndp, Nip, Nib and Pro:

and

n is an integer between 4 and 20; and at least one of the monomers in the peptoid oligomer is Nap, Nab, Nah, or Ngb.

2. A peptoid oligomer according to formula Ib

a salt, stereoisomers, isotopic variants, or tautomers thereof;
wherein
each R 1 is independently substituted or unsubstituted alkyl;
each R 2 is independently hydrogen, or substituted or unsubstituted alkyl; or
each R 1 and R 2 are joined together to form a 4-7 membered heterocyclic ring;
the said peptoid oligomer consists of one or more monomers selected from Nap, Nab, Nah, Ngb, Npm, Nnm, Ndp, Nip, Nib and Pro:

n is an integer between 4 and 20; and at least one of the monomers in the peptoid oligomer is Nap, Nab, Nah, or Ngb.

3. The method of claim 1 , wherein the disease or condition is or results from a bacterial infection.

4. The method of claim 1 , wherein the disease or condition is or results from a viral infection.

5. The method of claim 1 , wherein the disease or condition is or results from a fungal infection.

6. The method of claim 1 , wherein the disease or condition is or results from gram positive or gram negative bacterial strain infection.

7. The method of claim 1 , wherein the disease or condition is or results from abnormal behaviors of essential proteins.

8. The method of claim 1 , wherein the disease or condition is or results from Staphylococcus aureus, Streptococcus pneumoniae , or Pseudomonas aeruginosa infection.

9. The method of claim 1 , wherein the disease or condition is or results from Methicillin-resistant Staphylococcus aureus (MRSA) infection.

10. A method for generating an antiseptic or sterile environment, which comprises applying at least one peptoid oligomer according to claim 1 or a composition thereof to a surface of the environment to coat the surface, thereby generating the antiseptic or sterile environment.

11. An antimicrobial or pharmaceutical composition comprising at least one peptoid oligomer according to claim 2 .

12. An antimicrobial substrate comprising at least one peptoid oligomer according to claim 2 bound to or incorporated into the substrate.

13. An article comprising an antimicrobial substrate of claim 12 , wherein the article is selected from the group consisting of a personal care item, an agricultural item, a cosmetic, a package, a food handling item, a food delivery item, a personal garment, a medical device, a personal hygiene item, an article intended for oral contact, a household item, a toy, and a liquid separation article.

14. A method for treating, ameliorating or managing a disease or condition, which comprises administering to a patient in need of such treatment, amelioration or management a therapeutically acceptable amount of at least one peptoid oligomer according to claim 2 or a composition thereof to the patient.

15. A method for generating an antiseptic or sterile environment, which comprises applying at least one peptoid oligomer according to claim 2 or a composition thereof to a surface of the environment to coat the surface, thereby generating the antiseptic or sterile environment.

16. The peptoid oligomer according to claim 2 , wherein n is 6; and the said peptoid oligomer consists of three Ngb, Nah, Nap or Nab monomers; and three Ndp, Nnm, or Npm, monomers.

17. The peptoid oligomer according to claim 2 , wherein n is 6; and the said peptoid oligomer consists of four Nap monomers; and two Npm monomers.

18. The peptoid oligomer according to claim 2 , wherein n is 6; and the said peptoid oligomer consists of four Npm monomers; and two Nap monomers.

19. The peptoid oligomer according to claim 2 , wherein n is 6; and the said peptoid oligomer consists of four Ndp monomers; and two Ngb monomers.

20. The peptoid oligomer according to claim 2 , wherein n is 8; and the said peptoid oligomer consists of four Nap monomers; and four Npm monomers.

21. The peptoid oligomer according to claim 2 , wherein n is 10; and the said peptoid oligomer consists of two Nip monomers; two Nap monomers; two Nib monomers; two Npm monomers; and two Pro monomers.

22. The peptoid oligomer according to claim 2 , wherein n is 10; and the said peptoid oligomer consists of two Ndp monomers; two Nib monomers; two Ngb monomers; two Nip monomers; and two Pro monomers.

23. The peptoid oligomer according to claim 2 , wherein n is 10; and the said peptoid oligomer consists of two Npm monomers; two Nib monomers; two Nap monomers; two Nip monomers; and two Pro monomers.

24. The peptoid oligomer according to claim 2 , wherein n is 10; and the said peptoid oligomer consists of five Nap monomers; and five Npm monomers.

25. The peptoid oligomer according to claim 2 , wherein n is 10; and the said peptoid oligomer consists of five Ngb monomers; and five Ndp monomers.

26. The peptoid oligomer according to claim 2 , selected from the group consisting of:
C(NgbNpm) 3 ;
C(NahNpm) 3 ;
C(NapNdp) 3 ;
C(NapNnm) 3 ;
C(NapNpm) 2 Nap 2 ;
C(NapNpm) 3 ;
C(NapNpm) 4 ;
C(NapNpm) 5 ;
C(NpmNap) 2 Npm 2 ;
C(NipNapNibNpmPro) 2 ;
C(NdpNibNgbNipPro) 2 ;
C(NpmNibNapNipPro) 2 ;
C(NabNpm) 3 ;
C(NgbNdp) 5 ; and
C(NdpNgb) 2 Ndp 2
wherein C is cyclic.

27. The peptoid oligomer according to claim 2 , selected from the group consisting of:
C(NapNdp) 3 ;
C(NapNpm) 3 ; and
C(NapNpm) 5 ;
wherein C is cyclic.

28. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of the peptoid oligomer of claim 2 .

29. The pharmaceutical composition of claim 28 , wherein the carrier is a parenteral carrier, oral or topical carrier.

Assignees

• Kirshenbaum Kent
• Shin Sung Bin
• Univ New York

Inventors

• Kirshenbaum Kent
• Shin Sung Bin

Classifications

• A61P31/12

  Antivirals · CPC title

• A01N37/26

  containing the group [IMAGE cpc-sch-A01N-0936.gif]; Thio analogues thereof · CPC title

• A61K38/00

  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 title

• A01N43/713 Primary

  having rings with four or more nitrogen atoms as the only ring hetero atoms · CPC title

• C07K7/06

  having 5 to 11 amino acids · CPC title