Epimers of bicyclo[2.2.2]octan-2-ol derivatives with antiprotozoal activity.
(2SR,6RS,7RS)-4-Dialkylaminobicyclo[2.2.2]octan-2-ols and several of their esters have shown promising activity against the causative organisms for malaria and sleeping sickness. The base-catalyzed epimerization of the alcohols was carried out by different methods giving their (2RS,6RS,7RS)-isomers. Best results were obtained by the consecutive use of potassium tert-butoxide and sodium. The isomeric alcohols were converted to selected esters. All new compounds were tested for their activity against Trypanosoma brucei rhodesiense (STIB 900) and a multiresistant strain of Plasmodium falciparum. The antitrypanosomal activity and the cytotoxicity were in general increased. The most active antitrypanosomal agents were the benzoate 8b and the 4-chlorobenzoate 9b of the 4-pyrrolidino series. The nicotinate 10a and the isonicotinate 11a showed the highest antiplasmodial activities.
Schlapper
Christian
C
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.
Seebacher
Werner
W
Kaiser
Marcel
M
Brun
Reto
R
Saf
Robert
R
Weis
Robert
R
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010963:Plasmodium falciparum / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
D000981:Antiprotozoal Agents; D001643:Bridged Bicyclo Compounds