Prodrug derivatives of (E)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide
In part, the present disclosure is directed to prodrug derivatives of (E)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide compounds with significant solubility and bioavailability profiles.
1. A compound represented by:
or a pharmaceutically acceptable salt thereof.
2. A pharmaceutically acceptable composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
3. The pharmaceutically acceptable composition of claim 2 , wherein the composition is a powder, tablet, pill, or capsule.
4. The pharmaceutically acceptable composition of claim 2 , wherein the composition is a sterile aqueous composition.
5. A pharmaceutically acceptable composition suitable for oral administration, comprising a compound of claim 1 and a pharmaceutically acceptable excipient suitable for the oral administration.
6. A pharmaceutically acceptable composition for intravenous administration, comprising a compound of claim 1 and a pharmaceutically acceptable excipient suitable for the intravenous administration.
7. A compound represented by formula I:
wherein,
R 1 and R 2 are each independently selected from the group consisting of hydrogen, an alkali metal, NH 4 + , NH 3 + —(R 3 ), NH 2 + —(R 3 ) 2 , and NH + —(R 3 ) 3 , or R 1 and R 2 taken together are an alkaline earth metal; and
R 3 is independently selected from the group consisting of C 1-6 alkyl-, hydroxyC 1-6 alkyl-, phenyl and benzyl.
8. The compound of claim 7 , wherein R 1 and R 2 are each NH 3 + —(R 3 ).
9. The compound of claim 7 , wherein one of R 1 and R 2 is H; and one of R 1 and R 2 is NH 4 + or NH 3 + —(R 3 ).
10. The compound of claim 7 , wherein R 3 is —CH 2 CH 2 OH.
11. The compound of claim 7 , wherein R 1 and R 2 are an alkali metal.
12. The compound of claim 11 , wherein the alkali metal is selected from the group consisting of lithium, sodium and potassium.
13. The compound of claim 7 , wherein R 1 and R 2 taken together are an alkaline earth metal.
14. The compound of claim 13 , wherein the alkaline earth metal is calcium or magnesium.
15. The compound of claim 7 , wherein the compound is represented by:
16. The compound of claim 7 , wherein the compound is represented by:
17. The compound of claim 7 , wherein the compound is represented by:
18. The compound of claim 7 , wherein the compound is represented by:
19. A method of treating a Staphylococcus aureus bacterial infection, comprising administering to a patient in need thereof a composition of claim 2 to treat the Staphylococcus aureus bacterial infection.
20. The method of claim 19 , wherein the Staphylococcus aureus is methicillin-resistant.
21. The method of claim 19 , wherein the patient is a human.
22. The method of claim 19 , wherein administering is selected from the group consisting of orally administering, intravenously administering, subcutaneously administering, topically administering, and administration by inhalation.
23. The method of claim 19 , wherein administering is orally administering.
24. The method of claim 19 , wherein administering is intravenously administering or subcutaneously administering.
25. The method of claim 19 , further comprising administering to said patient a compound selected from the group consisting of an oxazolidinone, vancomycin, a glycopeptide, a penicillin, a cephalosporin, a pleuromutilin, a fusidane, a lincosamide, rifamycin, and arbekacin.
26. The method of claim 19 , further comprising administering to said patient a compound selected from the group consisting of linezolid, daptomycin, teicoplanin, and telavancin.
27. The method of claim 19 , further comprising administering to said patient a compound selected from the group consisting of quinolones, fluoroquinolones, carbapenems, aminoglycosides, tetracyclines, streptogramins, and macrolides.