Metallo-beta-lactamase inhibitors
The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, R A , X 1 , X 2 and R 1 are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.
1. A method of treating a bacterial infection which comprises administering to a subject in need thereof a therapeutically effective amount of a compound having the structure
or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of a beta-lactam antibiotic selected from the group consisting of imipenem, ertapenem, meropenem, doripenem, biapenem, panipenem, ticarcillin, ampicillin, amoxicillin, carbenicillin, piperacillin, azlocillin, mezlocillin, cefoperazone, cefotaxime, ceftriaxone, cefepime, ceftolozane, and ceftazidime.
2. The method of claim 1 , wherein the compound administered is
or a pharmaceutically acceptable salt thereof.
3. The method of claim 2 , wherein the beta-lactam antibiotic administered is imipenem.
4. The method of claim 2 , wherein the beta-lactam antibiotic administered is cefipime.
5. The method of claim 1 , wherein the compound administered is
or a pharmaceutically acceptable salt thereof.
6. The method of claim 5 , wherein the beta-lactam antibiotic administered is imipenem.
7. The method of claim 5 , wherein the beta-lactam antibiotic administered is cefipime.
8. The method of claim 1 , wherein the compound administered is
or a pharmaceutically acceptable salt thereof.
9. The method of claim 8 , wherein the beta-lactam antibiotic administered is imipenem.
10. The method of claim 8 , wherein the beta-lactam antibiotic administered is cefipime.
11. The method of claim 1 , wherein the compound administered is
or a pharmaceutically acceptable salt thereof.
12. The method of claim 11 , wherein the beta-lactam antibiotic administered is imipenem.
13. The method of claim 11 , wherein the beta-lactam antibiotic administered is cefipime.
14. The method of claim 11 , wherein the compound administered is
or a pharmaceutically acceptable salt thereof.
15. The method of claim 14 , wherein the beta-lactam antibiotic administered is imipenem.
16. The method of claim 14 , wherein the beta-lactam antibiotic administered is cefipime.
17. The method of claim 1 , wherein the compound administered is
or a pharmaceutically acceptable salt thereof.
18. The method of claim 17 , wherein the beta-lactam antibiotic administered is imipenem.
19. The method of claim 17 , wherein the beta-lactam antibiotic administered is cefipime.
20. A method of treating a bacterial infection which comprises administering to a subject in need thereof a therapeutically effective amount of a compound having the structure
or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of imipenem, cilastatin and relebactam.