title: Arylmethyl substituted derivatives of Fosmidomycin: synthesis and antimalarial activity.
abstract: The phosphonohydroxamic acid Fosmidomycin is a drug candidate for the treatment of Malaria, currently in phase II trials in combination with Clindamycin. In order to obtain compounds of higher lipophilicity, we recently synthesized alpha-phenyl substituted Fosmidomycin derivatives which display high antimalarial activity. We now report the synthesis and in vitro antimalarial activity of arylmethyl substituted bis(pivaloyloxymethyl) ester prodrugs of Fosmidomycin and its acetyl analogue FR900098. The 3,4-dichlorobenzyl substituted derivative of Fosmidomycin proved to be about twice as active as the respective Fosmidomycin prodrug, however, less active than the corresponding FR900098 prodrug. Electron donating substituents as well as voluminous substituents led to a significant reduction of activity.
authors.affiliation: Institute of Pharmacy, University of Hamburg, Bundesstrasse 45, D-20146 Hamburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schlüter
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Walter
authors.forename: Bärbel
authors.initials: B
authors.lastname: Bergmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Kurz
mesh_terms: D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D000962:Antimalarials; D005578:Fosfomycin; C024640:fosmidomycin