Patent
The present invention provides N-alkylthio β-lactams and disulfide compounds (e.g., alkyl-coenzyme A asymmetric disulfides or aryl-alkyl disulfides), compositions containing such compounds, and methods of their use as anti-bacterial agents.
1. A method for
i) treating a bacterial infection, comprising administering to a subject in need thereof an effective amount of a compound comprising an alkyl-coenzyme A asymmetric disulfide; or a compound having a chemical structure selected from:
or a pharmaceutically acceptable salt thereof, wherein R and R′ are the same or different, each being independently selected from the group consisting of H, alkyl, cycloalkyl, alkoxy, aryl, heteroaryl, heteroalkyl, alkanoyl, 2-aminoalkyl, 2-hydroxyalkyl, and halo; or a composition comprising the compound and a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the compound has the structure:
wherein R is alkyl.
3. The method of claim 1 , wherein the compound has the structure:
4. The method of claim 1 , wherein the compound has the structure:
5. The method of claim 1 , wherein the compound has the structure:
6. The method of claim 1 , wherein the compound has the structure:
7. The method of claim 1 , wherein the compound has the structure:
8. The method of claim 1 wherein the compound has the structure:
9. The method of claim 1 wherein the compound has the structure:
10. The method of claim 1 , wherein the subject is a human.
11. The method of claim 1 , wherein the bacterial infection is caused by Staphylococcus, Bacillus, Micrococcus, Streptococcus, Neisseria, Streptomyces , or Mycobacterium.
12. The method of claim 1 , wherein the bacterial infection is caused by Staphylococcus aureus, Bacillus anthracis, Escherichia coli , or Mycobacterium tuberculosis.
13. The method of claim 1 , wherein the bacterial infection is caused by methicillin-resistant Staphylococcus aureus.
14. The method of claim 1 , wherein R or R′ is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or sec-butyl.
15. A method for treating a bacterial infection, comprising administering to a subject in need thereof an effective amount of a compound, wherein the compound has the chemical structure I,
or a pharmaceutically acceptable salt thereof, wherein A and B are each electron withdrawing groups and are the same or different, and wherein R is selected from the group consisting of H, alkyl, cycloalkyl, alkoxy, aryl, heteroaryl, heteroalkyl, alkanoyl, 2-aminoalkyl, 2-hydroxyalkyl, and halo.
16. The method of claim 15 , wherein A and B are each independently selected from the group consisting of acyl, nitro, sulfonyl, amido, and imino.
17. The method of claim 15 , wherein the subject is a human.
18. The method of claim 15 , wherein the bacterial infection is caused by Staphylococcus, Bacillus, Micrococcus, Streptococcus, Neisseria, Streptomyces , or Mycobacterium.
19. The method of claim 15 , wherein the bacterial infection is caused by Staphylococcus aureus, Bacillus anthracis, Escherichia coli , or Mycobacterium tuberculosis.
20. The method of claim 15 , wherein the bacterial infection is caused by methicillin-resistant Staphylococcus aureus.
21. The method of claim 15 , wherein R is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, or sec-butyl.