Synthesis of 3-azabicyclo[3.2.2]nonanes and their antiprotozoal activities

  • Bioorg Med Chem Lett. 2015 Apr 1;25(7):1390-3. doi: 10.1016/j.bmcl.2015.02.044.
Werner Seebacher  1 ,  Volker Wolkinger  2 ,  Johanna Faist  2 ,  Marcel Kaiser  3 ,  Reto Brun  3 ,  Robert Saf  4 ,  Franz Bucar  5 ,  Barbara Gröblacher  5 ,  Adelheid Brantner  5 ,  Virginia Merino  6 ,  Yogeshvar Kalia  7 ,  Leonardo Scapozza  7 ,  Remo Perozzo  7 ,  Robert Weis  2
Affiliations
  • 1. Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Schubertstrasse 1, Graz A-8010, Austria. Electronic address: [email protected].
  • 2. Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Schubertstrasse 1, Graz A-8010, Austria.
  • 3. Swiss Tropical and Public Health Institute, Socinstrasse 57, Basel CH-4002, Switzerland; University of Basel, Petersplatz 1, Basel CH-4003, Switzerland.
  • 4. Institute for Chemistry and Technology of Materials (ICTM), Graz University of Technology, Stremayrgasse 9, Graz A-8010, Austria.
  • 5. Institute of Pharmaceutical Sciences, Pharmacognosie, Karl-Franzens-University, Universitätsplatz 4, Graz A-8010, Austria.
  • 6. Departamento de Farmacia y Tecnología Farmacéutica, University of Valencia, Valencia E-46000, Spain.
  • 7. School of Pharmaceutical Sciences, Pharmaceutical Biochemistry, University of Geneva, Quai Ernest-Ansermet 30, Geneva CH-1211, Switzerland.
PMID: 25746816 DOI: 10.1016/j.bmcl.2015.02.044
Abstract

Several bicyclic compounds, 3-azabicyclo[3.2.2]nonanes, have been prepared. The new compounds were tested for their activities against one strain of the causative organism of Malaria tropica, Plasmodium falciparum K1, which is resistant against chloroquine and pyrimethamine. In addition, their cytotoxicity and their activity against the pathogen of the East African form of sleeping sickness, Trypanosoma brucei rhodesiense, were investigated. Structure-activity relationships are discussed considering data of readily prepared compounds. For the first time, a distinct in vivo activity was observed against Plasmodium berghei in a mouse model. The active compound was further investigated.

Keywords
3-Azabicyclo[3.2.2]nonanes; Antiplasmodial activity; Antitrypanosomal activity.