Glycopeptide disulfide and thioester derivatives
View Patent ↗Disclosed are disulfide and thioester derivatives of glycopeptides and pharmaceutical compositions containing such glycopeptide derivatives. The disclosed glycopeptide derivatives are useful as antibacterial agents.
1. A glycopeptide of formula II:
wherein:
R 3 is —OH;
R 5 is hydrogen;
R 19 is hydrogen;
R 20 is —R a —S—(CO)—R h ;
R a is alkylene, alkenylene, alkynylene, cycloalkylene, cycloalkenylene arylene, heteroarylene, heterocyclene, —C(O)-alkylene, —C(O)-alkenylene —C(O)-alkynylene, —C(O)-cycloalkylene, —C(O)-cycloallcenylene —C(O)-arylene, —C(O)-heteroarylene or heterocyclene; and
R h is alkyl, alkenyl, alkynyl, cycloalkyl, cydoalkenyl, aryl, heteroaryl, or heterocyclic;
or a pharmaceutically acceptable salt, stereoisonier, or prodrug thereof.
2. The glycopeptide of claim 1 , wherein R a is alkylene, alkenylene, alkynylene, —C(O)-alkylene, —C(O)-alkenylene, or —C(O)-alkynylene, and R h is alkyl, alkenyl, or alkynyl.
3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 .
4. The pharmaceutical composition of claim 3 , where the composition further comprises a cyclodextrin.
5. The glycopeptide of claim 1 , wherein R a is alkylene.
6. The glycopeptide of claim 1 , wherein R h is alkyl.
7. A method of treating a mammal having a bacterial disease, the method comprising administering to the mammal a therapeutically effective amount of a glycopeptide of claim 1 , thereby effectively treating the bacterial disease.
8. A method of treating a mammal having a bacterial disease, the method comprising administering to the mammal a therapeutically effective amount of a pharmaceutical composition of claim 3 , thereby effectively treating the bacterial disease.