Oxazolidinone containing dimer compounds, compositions and methods to make and use
View Patent ↗Dosage forms or pharmaceutical compositions comprise a compound having the structure of Formula IV: wherein n is a non-negative integer; wherein each Z is an oxazolidinone-containing moiety having antibiotic activity in vivo upon cleaving, wherein M is independently OR 1 or NR 1 R 2 ; wherein R 1 and R 2 are independently selected from the group consisting of H, an optionally-substituted hydrocarbyl residue or a pharmaceutically acceptable cation; wherein the compound in the dosage form or a pharmaceutical composition is present in an amount effective for treating or preventing an antibacterial infection in a mammalian subject. Methods of preparing and using these dosage forms or pharmaceutical compositions are also disclosed.
1. A pharmaceutical composition comprising a therapeutically effective amount of a compound having the following structure
wherein each Z is
wherein * is the point of attachment of Z to P;
wherein M OR 1 ;
wherein R1 is H or a pharmaceutically acceptable cation.
2. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable cation is a sodium cation.
3. The pharmaceutical composition of claim 1 ,
wherein each Z is
4. The pharmaceutical composition of claim 1 , further comprising a pharmaceutically acceptable carrier, diluent or excipient.
5. The pharmaceutical composition of claim 2 , wherein the structure is:
or the sodium salt thereof.
6. A method of preparing the compound in the pharmaceutical composition of claim 1 , comprising the step of treating a compound of the formula Z—H with a phosphorylating agent.
7. A method of preparing the compound in the pharmaceutical composition of claim 1 , comprising the step of treating with a dehydrating agent the compound Z—P′, wherein P′ is a mono-or dihydrogen phosphate group.
8. The method of claim 6 , wherein the phosphorylating agent is POCl 3 .
9. A method of treating a bacterial infection comprising
administering the pharmaceutical composition of claim 1 to a subject in need thereof.
10. A method of treating a bacterial infection comprising
administering the pharmaceutical composition of claim 2 to a subject in need thereof.
11. A method of treating a bacterial infection comprising
administering the pharmaceutical composition of claim 4 to a subject in need thereof.
12. A method of treating a bacterial infection comprising
administering the pharmaceutical composition of claim 5 to a subject in need thereof.
13. The pharmaceutical composition of claim 2 , further comprising a pharmaceutically acceptable carrier, diluent or excipient.
14. The pharmaceutical composition of claim 5 , further comprising a pharmaceutically acceptable carrier, diluent or excipient.