Berger Heinrich, Weis Robert, Kaiser Marcel, Brun Reto, Saf Robert, Seebacher Werner
Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.
Bioorg Med Chem. 2008 Jun 15;16(12):6371-8. doi: 10.1016/j.bmc.2008.05.007. Epub 2008 May 7.
New diaryl substituted 2-azabicyclo[3.2.2]nonane derivatives have been synthesized in order to investigate the influence of the aromatic substitution and of N substitution on the antiprotozoal activities of those compounds. Following a manual method for the Hansch approach, different 4-substituted aryl rings were systematically inserted, and moieties with varying basicity and polarity were attached to the ring nitrogen. All compounds were investigated for their activities against Trypanosoma brucei rhodesiense (STIB 900) and the K(1) strain of Plasmodium falciparum (resistant to chloroquine and pyrimethamine) and for their cytotoxicity using microplate assays. Some of the new compounds are amongst the most active antitrypanosomal agents in this series, and the selectivity index of a single derivative is superior in the 2-azabicyclo-nonane series.
为了研究芳基取代和氮取代对这些化合物抗寄生虫活性的影响，已合成了新型二芳基取代的2-氮杂双环[3.2.2]壬烷衍生物。按照Hansch方法的手工操作流程，系统地引入了不同的4-取代芳基环，并将具有不同碱度和极性的基团连接到环氮上。使用微孔板分析法研究了所有化合物对布氏罗得西亚锥虫（STIB 900）和恶性疟原虫K(1)株（对氯喹和乙胺嘧啶耐药）的活性以及它们的细胞毒性。一些新化合物是该系列中最具活性的抗锥虫剂，且单一衍生物的选择性指数在2-氮杂双环壬烷系列中是最优的。
