title: Synthesis and evaluation of alpha-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (FR900098) as antimalarials.
abstract: Three alpha-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (FR900098) have been synthesized from diethyl but-3-enylphosphonate using a previously described method for the alpha-halogenation of alkylphosphonates. These analogues were evaluated for antimalarial potential in vitro against Plasmodium falciparum and in vivo in the P. berghei mouse model. All three analogues showed higher in vitro and/or in vivo potency than the reference compounds.
authors.affiliation: Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Verbrugghen
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000208:Acute Disease; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005578:Fosfomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D005578:Fosfomycin; C024639:3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid