Boronic acid derivatives and therapeutic uses thereof
Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the method of use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents, for example, β-lactamase inhibitors (BLIs).
1. A compound having the structure
or a pharmaceutically acceptable salt thereof.
2. The compound claim 1 , wherein the pharmaceutically acceptable salt is an alkaline metal salt or an ammonium salt.
3. The compound of claim 2 , wherein the pharmaceutically acceptable salt is a sodium salt.
4. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
5. The pharmaceutical composition of claim 4 , further comprising an additional medicament.
6. The pharmaceutical composition of claim 5 , wherein the additional medicament is a β-lactam antibacterial agent.
7. The pharmaceutical composition of claim 6 , wherein the β-lactam antibacterial agent is Meropenem, or a pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition of claim 6 , wherein the β-lactam antibacterial agent is Ceftibuten, or a pharmaceutically acceptable salt thereof.
9. A method of treating a bacterial infection caused by β-lactam antibacterial agent-resistant enterobacteriaceae, comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof to a subject in need thereof.
10. The method of claim 9 , further comprising administering a β-lactam antibacterial agent to the subject.
11. The method of claim 10 , wherein the β-lactam antibacterial agent is Meropenem or Ceftibuten, or pharmaceutically acceptable salts thereof.
12. The method of claim 10 , wherein the β-lactam antibacterial agent is administered separately from the compound or pharmaceutically acceptable salt thereof.
13. The method of claim 10 , wherein the β-lactam antibacterial agent and the compound or pharmaceutically acceptable salt thereof are in a single dosage form.
14. A method of treating a bacterial infection caused by β-lactam antibacterial agent-resistant enterobacteriaceae, comprising administering a pharmaceutical composition comprising therapeutically effective amounts of a compound of the structure
and Meropenem, or pharmaceutically acceptable salts thereof to a subject in need thereof.
15. The method of claim 14 , wherein the pharmaceutical composition is administered intravenously.
16. A method of treating a bacterial infection caused by β-lactam antibacterial agent-resistant enterobacteriaceae, comprising administering a pharmaceutical composition comprising therapeutically effective amounts of a compound of the structure
and Ceftibuten, or pharmaceutically acceptable salts thereof to a subject in need thereof.
17. The method of claim 16 , wherein the pharmaceutical composition is administered orally.
18. The method of claim 9 , wherein the bacterial infection is caused by Carbapenem-resistant enterobacteriaceae.
19. The method of claim 9 , wherein the bacterial infection is caused by Klebsiella, Pseudomonas, Escherichia, Enterobacter or Acinetobacter.
20. The method of claim 9 , wherein the bacterial infection is caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae , or Acinetobacter baumannii.
21. The method of claim 14 , wherein the bacterial infection is caused by Carbapenem-resistant enterobacteriaceae.
22. The method of claim 14 , wherein the bacterial infection is caused by Klebsiella, Pseudomonas, Escherichia, Enterobacter or Acinetobacter.
23. The method of claim 14 , wherein the bacterial infection is caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae , or Acinetobacter baumannii.
24. The method of claim 16 , wherein the bacterial infection is caused by Carbapenem-resistant enterobacteriaceae.
25. The method of claim 16 , wherein the bacterial infection is caused by Klebsiella, Pseudomonas, Escherichia, Enterobacter or Acinetobacter.
26. The method of claim 16 , wherein the bacterial infection is caused by Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae , or Acinetobacter baumannii.