Lipo-glycopeptide cleavable derivatives and uses thereof
The present invention provides certain lipo-glycopeptide cleavable derivatives and methods for using the same for the treatment of bacterial infections, for example, pulmonary bacterial infections. The LGPC derivatives include a cleavable moiety that in certain embodiments, is designed to allow for cellular uptake and/or a more rapid clearance of the glycopeptide metabolite (i.e., the cleaved glycopeptide) from the site of administration (e.g., the lung) as compared to the uncleaved LGPC.
1. A method for treating a Gram-positive pulmonary bacterial infection in a patient in need thereof, the method comprising:
administering to the lungs of the patient via a nebulizer, dry powder inhaler (DPI) or metered dose inhaler (MDI), a composition comprising an effective amount of a compound of Formula (II), or a pharmaceutically acceptable salt thereof:
wherein,
R 1 is —(CH 2 ) n1 —O—C(O)—(CH 2 ) n2 —CH 3 ;
n 1 is 2;
n 2 is 12;
R 2 is OH;
R 3 is H; and
R 4 is H.
2. The method of claim 1 , wherein the administering is carried out via a dry powder inhaler.
3. The method of claim 1 , wherein the Gram-positive pulmonary bacterial infection is a Gram-positive pulmonary cocci infection.
4. The method of claim 3 , wherein the Gram-positive pulmonary cocci infection is a Staphylococcus pulmonary infection.
5. The method of claim 3 , wherein the Gram-positive pulmonary cocci infection is an Enterococcus pulmonary infection.
6. The method of claim 3 , wherein the Gram-positive pulmonary cocci infection is a Streptococcus pulmonary infection.
7. The method of claim 4 , wherein the Staphylococcus pulmonary infection is a Staphylococcus aureus ( S. aureus ) pulmonary infection.
8. The method of claim 7 , wherein the S. aureus pulmonary infection is a methicillin-resistant S. aureus (MRSA) pulmonary infection.
9. The method of claim 2 , wherein the Gram-positive pulmonary bacterial infection is a Gram-positive pulmonary cocci infection.
10. The method of claim 9 , wherein the Gram-positive pulmonary cocci infection is a Staphylococcus pulmonary infection.
11. The method of claim 9 , wherein the Gram-positive pulmonary cocci infection is an Enterococcus pulmonary infection.
12. The method of claim 9 , wherein the Gram-positive pulmonary cocci infection is a Streptococcus pulmonary infection.
13. The method of claim 10 , wherein the Staphylococcus pulmonary infection is a Staphylococcus aureus ( S. aureus ) pulmonary infection.
14. The method of claim 13 , wherein the S. aureus pulmonary infection is a methicillin-resistant S. aureus (MRSA) pulmonary infection.
15. The method of claim 1 , wherein the patient is a cystic fibrosis patient.
16. The method of claim 2 , wherein the patient is a cystic fibrosis patient.
17. The method of claim 8 , wherein the patient is a cystic fibrosis patient.
18. The method of claim 14 , wherein the patient is a cystic fibrosis patient.