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Alkoxycarbonyloxyethyl Ester Prodrugs of FR900098 with Improved In Vivo Antimalarial Activity
Author(s) -
Ortmann Regina,
Wiesner Jochen,
Reichenberg Armin,
Henschker Dajana,
Beck Ewald,
Jomaa Hassan,
Schlitzer Martin
Publication year - 2005
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200500976
Subject(s) - prodrug , chemistry , moiety , mechanism of action , in vivo , biochemistry , pharmacology , enzyme , stereochemistry , in vitro , biology , microbiology and biotechnology
FR900098 represents a derivative of the new antimalarial drug fosmidomycin with enhanced activity. The mechanism of action is the inhibition of the 1‐desoxy‐ D ‐xylulose 5‐phosphate (DOXP) reductoisomerase, an essential enzyme of the mevalonate independent pathway of isoprenoid biosynthesis. Prodrugs with increased oral activity in mice infected with the rodent malaria parasite Plasmodium vinckei were obtained by masking the phosphonate moiety of FR900098 as alkoxycarbonyloxyethyl esters.