Dialkylaminoalkyl derivatives of bicyclic compounds with antiplasmodial activity.
Dialkylaminoalkyl derivatives of 2-azabicyclo[3.2.2]nonanes and of bicyclo[2.2.2]octanes were prepared and their activities determined in vitro against the multiresistant K1 strain of Plasmodium falciparum. Several of the new compounds exhibited very promising antiplasmodial activity and selectivity. The results were compared to those of formerly synthesized analogues and of drugs in use. Structure-activity relationships were detected. Some of the more potent compounds were tested in vivo against Plasmodium berghei showing weak to moderate activity. A single compound was able to increase the mean survival days of infected mice.
Faist
Johanna
J
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Universitätsplatz 1, A-8010 Graz, Austria.
Seebacher
Werner
W
Kaiser
Marcel
M
Brun
Reto
R
Saf
Robert
R
Weis
Robert
R
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004195:Disease Models, Animal; D051379:Mice; D032448:Myoblasts, Skeletal / Q000187:drug effects; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship
D000962:Antimalarials; D053961:Azabicyclo Compounds; D001643:Bridged Bicyclo Compounds