Antimicrobial compounds

Patent metadata

Field	Value
Publication number	US-9969758-B2
Application number	US-201515127564-A
Country	US
Kind code	B2
Filing date	Mar 23, 2015
Priority date	Mar 21, 2014
Publication date	May 15, 2018
Grant date	May 15, 2018

Abstract

An antimicrobial compound, as well as the salts, derivatives and analogs thereof, said compound being represented by the general formula (I):

wherein R 1 represents a peptide part P1 or a peptide part P2.

First claim

The invention claimed is:

1. An antimicrobial compound of formula (I):

or a salt thereof,
wherein R 1 is:
a peptide part P1 consisting of a linear sequence of one to five amino acid residues, wherein at least one of the amino acid residues is a β-chloroalanine residue; or
a peptide part P2 of formula (II):

wherein X is hydrogen or chlorine, and
Y is hydrogen or a linear sequence of one to four amino acid residues; and
wherein if X is hydrogen, Y is not hydrogen and an alanine residue is not in the N-terminal position of the linear amino acid sequence or bound to another amino acid residue via a peptide bond between the α amino function of the alanine residue and the α carboxylic acid function of another amino acid residue.

2. The antimicrobial compound of claim 1 , wherein at least one of the amino acid residues of the linear sequence of one to four amino acid residues Y is selected from a β-chloroalanine residue, a norvaline residue, and a methionine residue.

3. The antimicrobial compound of claim 1 , wherein the β-chloroalanine residue is a β-chloro-L-alanine residue.

4. The antimicrobial compound of claim 2 , wherein the β-chloroalanine residue is a β-chloro-L-alanine residue.

5. The antimicrobial compound of claim 2 , wherein the norvaline residue is a L-norvaline residue.

6. The antimicrobial compound of claim 2 , wherein the methionine residue is a L-methionine residue.

7. The antimicrobial compound of claim 1 , wherein R 1 is represented by the general formula (III):

wherein R 2 is hydrogen or a linear sequence of one to four amino acid residues.

8. The antimicrobial compound of claim 7 , wherein at least one of the amino acid residues is selected from a β-chloroalanine residue, a norvaline residue, and a methionine residue.

9. The antimicrobial compound of claim 8 , wherein the β-chloroalanine residue is a β-chloro-L-alanine residue.

10. The antimicrobial compound of claim 8 , wherein the norvaline residue is a L-norvaline residue.

11. The antimicrobial compound of claim 8 , wherein the methionine residue is a L-methionine residue.

12. The antimicrobial compound of claim 1 , wherein R 1 is represented by the general formula (IV):

wherein R 3 is hydrogen or a linear sequence of one to three amino acid residues.

13. The antimicrobial compound of claim 12 , wherein at least one of the amino acid residues is a β-chloroalanine residue.

14. The antimicrobial compound of claim 13 , wherein the β-chloroalanine residue is a β-chloro-L-alanine residue.

15. The antimicrobial compound of claim 1 , wherein R 1 is a linear chain of two or three amino acid residues.

16. The antimicrobial compound of claim 15 , wherein R 1 is a linear chain of two amino acid residues.

17. The antimicrobial compound of claim 1 , wherein the amino acid residue(s) is/are selected from the group consisting of: glycine, sarcosine, β-chloro-L-alanine, β-chloro-D-alanine, D/L-alanine, D/L-arginine, D/L-asparagine, D/L-aspartic acid, D/L-cysteine, D/L-glutamic acid, D/L-gamma-glutamic acid, D/L-glutamine, D/L-histidine, D/L-isoleucine, D/L-leucine, D/L-lysine, D/L-methionine, D/L-norvaline, D/L-phenylalanine, D/L-proline, D/L-pyroglutamic acid, D/L-serine, D/L-threonine, D/L-tryptophan, D/L-tyrosine, and D/L-valine.

18. The antimicrobial compound of claim 17 , wherein the amino acid residue(s) is/are selected from β-chloro-L-alanine, L-alanine, L-arginine, L-asparagine, L-aspartic acid, L-cysteine, L-glutamic acid, L-gamma-glutamic acid, L-glutamine, L-histidine, L-isoleucine, L-leucine, L-lysine, L-methionine, L-norvaline, L-phenylalanine, L-proline, L-pyroglutamic acid, L-serine, L-threonine, L-tryptophan, L-tyrosine, and L-valine.

19. The antimicrobial compound of claim 17 , wherein the amino acid residue(s) is/are selected from β-chloro-L-alanine, β-chloro-D-alanine, D/L-alanine, D/L-methionine, D/L-norvaline, and D/L-valine.

20. The antimicrobial compound of claim 1 , wherein R 1 is the peptide part P2 and X is hydrogen.

21. The antimicrobial compound of claim 20 , wherein Y is one amino acid residue selected from: glycine, sarcosine, β-chloro-L-alanine, β-chloro-D-alanine, D/L-arginine, D/L-asparagine, D/L-aspartic acid, D/L-cysteine, D/L-glutamic acid, D/L-gamma-glutamic acid, D/L-glutamine, D/L-histidine, D/L-isoleucine, D/L-leucine, D/L-lysine, D/L-methionine, D/L-norvaline, D/L-phenylalanine, D/L-proline, D/L-pyroglutamic acid, D/L-serine, D/L-threonine, D/L-tryptophan, D/L-tyrosine, and D/L-valine.

22. The antimicrobial compound of claim 21 , wherein the amino acid residue is selected from a L-methionine residue and a L-norvaline residue.

23. The antimicrobial compound of claim 1 , wherein the antimicrobial compound is selected from:
β-chloro-L-alanyl-D/L-1-aminoethylphosphonic acid;
β-chloro-L-alanyl-β-chloro-L-alanyl-D/L-1-aminoethylphosphonic acid;
L-norvalinyl-β-chloro-L-alanyl-D/L-1-aminoethylphosphonic acid;
L-methionyl-β-chloro-L-alanyl-D/L-1-aminoethylphosphonic acid;
L-norvalinyl-L-alanyl-D/L-1-aminoethylphosphonic acid; and
L-methionyl-L-alanyl-D/L-1-aminoethylphosphonic acid.

24. The antimicrobial compound of claim 1 , wherein the antimicrobial compound is selected from:
β-chloro-L-alanyl-L-1-aminoethylphosphonic acid;
β-chloro-L-alanyl-β-chloro-L-alanyl-L-1-aminoethylphosphonic acid;
L-norvalinyl-β-chloro-L-alanyl-L-1-aminoethylphosphonic acid;
L-methionyl-β-chloro-L-alanyl-L-1-aminoethylphosphonic acid;
L-norvalinyl-L-alanyl-L-1-aminoethylphosphonic acid; and
L-methionyl-L-alanyl-L-1-aminoethylphosphonic acid.

25. The antimicrobial compound of claim 1 , wherein the antimicrobial compound is selected from:
β-chloro-L-alanyl-L-1-aminoethylphosphonic acid; and
β-chloro-L-alanyl-β-chloro-L-alanyl-L-1-aminoethylphosphonic acid.

26. The antimicrobial compound of claim 1 , wherein the amino function of the N-terminal amino acid residue of P1 or P2 is protected by a protecting group selected from: a tertiobutylocarbonyl group, a 9-fluorenylmethoxycarbonyl group and a benzyloxycarbonyl group.

27. A reaction medium comprising at least one antimicrobial compound of claim 1 .

28. The reaction medium of claim 27 , wherein the final concentration of the antimicrobial compound is between 0.002 mg/L and 1024.0 mg/L.

29. The reaction medium of claim 28 , wherein the final concentration of the antimicrobial compound is between 0.003 mg/L and 32.0 mg/L.

30. The reaction medium of claim 29 , wherein the final concentration of the antimicrobial compound is between 0.2 mg/L and 8.0 mg/L.

31. The reaction medium of claim 30 , wherein the final concentration of the antimicrobial compound is between 0.2 and 2.0 mg/L.

32. The reaction medium of claim 27 , wherein the reaction medium further comprises:
at least one target microorganism.

33. The reaction medium of claim 32 , whe

Assignees

• Biomerieux Sa

Inventors

• Anderson Rosaleen Joy
• Bedernjak Alexandre F
• Cellier Marie
• Ng Keng Tiong
• Orenga Sylvain
• Perry John D
• Varadi Linda

Classifications

• C07K5/0827

  containing heteroatoms different from O, S, or N · CPC title

• C07K5/1027

  containing heteroatoms different from O, S, or N · CPC title

• C07K5/06191 Primary

  containing heteroatoms different from O, S, or N · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• C12Q1/04

  Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)} · CPC title