Publication
Title
Synthesis of - and -oxa isosteres of fosmidomycin and FR900098 as antimalarial candidates
Author
Abstract
To expand the structureactivity relationships of fosmidomycin and FR900098, two potent antimalarials interfering with the MEP-pathway, we decided to replace a methylene group in β-position of the phosphonate moiety of these leads by an oxygen atom. β-oxa-FR900098 (11) proved equally active as the parent compound. When applied to 4-[hydroxyl(methyl)amino]-4-oxobutyl phosphonic acid, featuring a hydroxamate instead of the retrohydroxamate moiety, a β-oxa modification yielded a derivative (13) with superior activity against the Plasmodium falciparum 3D7 strain than fosmidomycin, while a γ-oxa modification resulted in less active derivatives. A bis(pivaloyloxymethyl)ester of phosphonate 13 proved twice as active in inhibiting cultured parasites as a similar prodrug of FR900098.
Language
English
Source (journal)
Bioorganic and medicinal chemistry. - Oxford
Publication
Oxford : 2008
ISSN
0968-0896
Volume/pages
16:6(2008), p. 3361-3371
ISI
000255127700062
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 28.11.2014
Last edited 14.06.2017