The synthesis of water soluble prodrugs analogs of echinocandin B.
A facile synthesis of phosphonate and phosphate ester prodrugs on the phenolic hydroxy of two echinocandin semisynthetic derivatives is reported. The water solubility and stability profiles of the ECB compounds varied with the choice of alkyl group used. In some cases, the ester prodrugs with small aliphatic side chains retained antifungal activity while enhancing water solubility.
Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, IN 46285, USA.
M J
MJ
Rodriguez
V
V
Vasudevan
J A
JA
Jamison
P S
PS
Borromeo
W W
WW
Turner
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D054714:Echinocandins; D005656:Fungal Proteins; D006863:Hydrogen-Ion Concentration; D063065:Organophosphonates / Q000737:chemistry; D010455:Peptides; D010456:Peptides, Cyclic; D010710:Phosphates / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D013696:Temperature; D014867:Water / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D054714:Echinocandins; D005656:Fungal Proteins; D063065:Organophosphonates; D010455:Peptides; D010456:Peptides, Cyclic; D010710:Phosphates; D011355:Prodrugs; D014867:Water; C007572:echinocandin B