Synthesis and evaluation of alpha-halogenated analogues of 3-(acetylhydroxyamino)propylphosphonic acid (FR900098) as antimalarials.
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.
Verbrugghen
Thomas
T
Laboratory for Medicinal Chemistry (FFW), Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
Cos
Paul
P
Maes
Louis
L
Van Calenbergh
Serge
S
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
D000962:Antimalarials; D005578:Fosfomycin; C024639:3-(N-acetyl-N-hydroxy)aminopropylphosphonic acid