Beta-lactamase inhibitors and uses thereof
β-Lactamase inhibiting compounds, therapeutic methods of using the β-lactamase inhibiting compounds, particularly in combination with β-lactam antibiotics and pharmaceutical compositions thereof are disclosed. The β-lactamase inhibiting compounds are suitable for oral administration.
1. A compound of Formula (1):
or a pharmaceutically acceptable salt thereof, wherein,
each R 1 is independently selected from C 1-6 alkyl; and
R 3 is C 1-6 alkyl.
2. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable vehicle.
3. The pharmaceutical composition of claim 2 , further comprising an antibiotic.
4. The pharmaceutical composition of claim 3 , wherein the antibiotic comprises a β-lactam antibiotic.
5. The pharmaceutical composition of claim 3 , wherein the antibiotic comprises ceftibuten, amoxicillin, or a combination thereof.
6. The pharmaceutical composition of claim 2 , wherein the pharmaceutical composition is an oral dosage formulation.
7. A method of treating a bacterial infection in a patient comprising administering to a patient having said infection a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof; and a therapeutically effective amount of a β-lactam antibiotic, wherein bacteria causing the bacterial infection produce a β-lactamase.
8. The method of claim 7 , wherein administering comprises orally administering.
9. The method of claim 7 , wherein the β-lactam antibiotic comprises ceftibuten, amoxicillin, or a combination thereof.
10. A method of treating a bacterial infection in a patient comprising administering to a patient having said infection a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a β-lactam antibiotic, wherein the bacterial infection is capable of being treated with a therapeutically effective amount of the β-lactam antibiotic when co-administered with a therapeutically effective amount of avibactam.
11. The method of claim 10 , wherein administering comprises orally administering.
12. The method of claim 10 , wherein the β-lactam antibiotic comprises ceftibuten, amoxicillin, or a combination thereof.
13. A compound, ethyl 3-(((((1R,2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl)oxy)sulfonyl)oxy)-2,2-dimethylpropanoate) or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising the compound of claim 13 and a pharmaceutically acceptable vehicle.
15. The pharmaceutical composition of claim 14 , further comprising an antibiotic.
16. The pharmaceutical composition of claim 15 , wherein the antibiotic comprises a β-lactam antibiotic.
17. The pharmaceutical composition of claim 15 , wherein the antibiotic comprises ceftibuten, amoxicillin, or a combination thereof.
18. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition is an oral dosage formulation.
19. A method of treating a bacterial infection in a patient comprising administering to a patient having said infection a therapeutically effective amount of the compound of claim 13 or a pharmaceutically acceptable salt thereof; and a therapeutically effective amount of a β-lactam antibiotic, wherein bacteria causing the bacterial infection produce a β-lactamase.
20. The method of claim 19 , wherein administering comprises orally administering.
21. The method of claim 19 , wherein the β-lactam antibiotic comprises ceftibuten, amoxicillin, or a combination thereof.
22. A method of treating a bacterial infection in a patient comprising administering to a patient having said infection a therapeutically effective amount of the compound of claim 13 or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of a β-lactam antibiotic, wherein the bacterial infection is capable of being treated with a therapeutically effective amount of the β-lactam antibiotic when co-administered with a therapeutically effective amount of avibactam.
23. The method of claim 22 , wherein administering comprises orally administering.
24. The method of claim 22 , wherein the β-lactam antibiotic comprises ceftibuten, amoxicillin, or a combination thereof.