Glycopeptide carboxy-saccharide derivatives
View Patent ↗Disclosed are glycopeptide derivatives substituted at the C-terminus and/or the R-terminus with a substituent that comprises one or more saccharide groups and a carboxy group; and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.
1. A method of modifying a glycopeptide antibiotic to form a glycopeptide antibiotic derivative having reduced tissue accumulation when administered to a mammal, the method comprising forming a carboxy-saccharide derivative of the glycopeptide antibiotic that has a substituent comprising a dicarboxylic acid in which one of the carboxylic acid groups is coupled with a saccharide.
2. The method of claim 1 , wherein the glycopeptide antibiotic is vancomycin or a derivative thereof.
3. The method of claim 1 , wherein the glycopeptide antibiotic is chloroorienticin A or a derivative thereof.
4. The method of claim 1 , wherein the glycopeptide antibiotic is teicoplanin or a derivative thereof.
5. The method of claim 1 , wherein the substituent is a substituent of formula III:
wherein one of R g and R h is a saccharide, and the other of R g and R h is OH.
6. The method of claim 1 , wherein the substituent is a substituent of formula IV:
wherein one of R m and R n is a saccharide, and the other is OH.
7. The method of claim 1 , wherein the substituent is a substituent of formula (i):
8. The method of claim 1 , wherein the substituent is a substituent of formula (ii):
9. The method of claim 1 , wherein the substituent is a substituent of formula (iii):
10. The method of claim 1 , wherein the substituent is a substituent of formula (iv):
11. A method of modifying a glycopeptide antibiotic to farm a glycopeptide antibiotic derivative having increased urinary clearance when administered to a mammal, the method comprising forming a carboxy-saccharide derivative of the glycopeptide antibiotic that has a substituent comprising a dicarboxylic acid in which one of the carboxylic acid groups is coupled with a saccharide.
12. The method of claim 11 , wherein the glycopeptide antibiotic is vancomycin or a derivative thereof.
13. The method of claim 11 , wherein the glycopeptide antibiotic is chloroorienticin A or a derivative thereof.
14. The method of claim 11 , wherein the glycopeptide antibiotic is teicoplanin or a derivative thereof.
15. The method of claim 11 , wherein the substituent is a substituent of formula III:
wherein one of R g and R h is a saccharide, and the other R g and R h is OH.
16. The method of claim 11 , wherein the substituent is a substituent of formula IV:
wherein one of R m and R n is a saccharide, and the other is OH.
17. The method of claim 11 , wherein the substituent is a substituent of formula (i):
18. The method of claim 11 , wherein the substituent is a substituent of formula (ii):
19. The method of claim 11 , wherein the substituent is a substituent of formula (iii):
20. The method of claim 11 , wherein the substituent is a substituent of formula (iv):