Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity.
The fosmidomycin derivative FR900098 represents an inhibitor of the 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase with potent antimalarial activity. Prodrugs of FR900098 with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield phosphodiaryl esters. One diaryl ester prodrug demonstrated efficacy in mice infected with the rodent malaria parasite Plasmodium vinckei comparable to i.p. drug administration.
Jomaa Pharmaka GmbH, Giessen, Germany.
A
A
Reichenberg
J
J
Wiesner
C
C
Weidemeyer
E
E
Dreiseidler
S
S
Sanderbrand
B
B
Altincicek
E
E
Beck
M
M
Schlitzer
H
H
Jomaa
D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors; D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005578:Fosfomycin / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use*; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D063065:Organophosphonates / Q000737:chemistry; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D010961:Plasmodium / Q000187:drug effects; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome
D000962:Antimalarials; D009097:Multienzyme Complexes; D063065:Organophosphonates; D011355:Prodrugs; D005578:Fosfomycin; C024639:3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases