Seebacher Werner, Schlapper Christian, Brun Reto, Kaiser Marcel, Saf Robert, Weis Robert
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens University, Universitätsplatz 1, A-8010 Graz, Austria.
Eur J Pharm Sci. 2005 Mar;24(4):281-9. doi: 10.1016/j.ejps.2004.11.003. Epub 2004 Dec 29.
Several bicyclo[2.2.2]octan-2-imines and esters of bicyclo[2.2.2]octan-2-ols were prepared. Their antitrypanosomal and antiplasmodial activities against Trypanosoma brucei rhodesiense (STIB 900) and the K1 strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) were determined using microplate assays. Two of the synthesized bicyclo[2.2.2]octan-2-one 4'-phenylthiosemicarbazones showed the highest antitrypanosomal activity (IC(50)<0.3 microM) of the so far prepared 4-amino-6,7-diarylbicyclo[2.2.2]octane derivatives, but they are distinctly less active than suramine (IC(50)=0.0075 microM). Most of the 4'-phenylthiosemicarbazones and a single bicyclo[2.2.2]octan-2-yl benzoate exhibit attractive antimalarial activity (IC(50)=0.23-0.72 microM). Two bicyclooctanone oximes are even as active as chloroquine (IC(50)=0.08-0.15 microM, chloroquine: IC(50)=0.12 microM against sensitive strains).
制备了几种双环[2.2.2]辛烷-2-亚胺和双环[2.2.2]辛烷-2-醇酯。使用微孔板分析法测定了它们对布氏罗得西亚锥虫（STIB 900）和恶性疟原虫K1株（对氯喹和乙胺嘧啶耐药）的抗锥虫和抗疟活性。所合成的两种双环[2.2.2]辛烷-2-酮4'-苯硫代氨基脲在迄今制备的4-氨基-6,7-二芳基双环[2.2.2]辛烷衍生物中显示出最高的抗锥虫活性（IC(50)<0.3 microM），但它们的活性明显低于苏拉明（IC(50)=0.0075 microM）。大多数4'-苯硫代氨基脲和一种双环[2.2.2]辛烷-2-基苯甲酸酯表现出有吸引力的抗疟活性（IC(50)=0.23 - 0.72 microM）。两种双环辛酮肟的活性甚至与氯喹相当（IC(50)=0.08 - 0.15 microM，氯喹：对敏感株的IC(50)=0.12 microM）。
