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Antiprotozoal activity of bicycles featuring a dimethylamino group at their bridgehead
Institution:1. Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Schubertstraße 1, A-8010 Graz, Austria;2. Institute for Chemistry and Technology of Materials (ICTM), Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria;3. Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland;4. University of Basel, Petersplatz 1, 4003 Basel, Switzerland;1. Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation;2. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation;3. State Key Laboratory of Chemical Engineering, Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P. R. China;1. Graduate Aeronautical Laboratories, California Institute of Technology, Pasadena, USA;2. Institut de Combustion, Aérothermique, Réactivité et Environnement (ICARE), Centre National de la Recherche Scientifique (CNRS), Orléans, France;1. Center for Degradable and Flame-Retardant Polymeric Materials, College of Chemistry, State Key Laboratory of Polymer Materials Engineering, National Engineering Laboratory of Eco-Friendly Polymeric Materials (Sichuan), Analytical and Testing Center, Sichuan University, Chengdu 610064, China;2. Bundesanstalt für Materialforschung und –prüfung (BAM), Unter den Eichen 87, Berlin 12205, Germany;1. Institute of Toxicology, School of Public Health, Shandong University, Jinan, Shandong 250012, China;2. Jinan Municipal Center for Disease Control & Prevention, Jinan, Shandong Province, China;3. North East Regional Health Authority, Ocho Rios, Jamaica
Abstract:Several dimethylamino-derivatives of the new compound-class 3-azabicyclo3.2.2]nonanes were prepared. For better comparison of activity also a few analogues of bicyclo2.2.2]octanes and 2-azabicyclo3.2.2]nonanes were synthesized. Their activities were examined in vitro against the multiresistant K1 strain of Plasmodium falciparum and against Trypanosoma brucei rhodesiense (STIB 900). A couple of the newly synthesized compounds showed promising antiprotozoal activity and selectivity. The results of the biological tests of the novel compounds were compared with the activities of already synthesized compounds and of drugs in use. Structure–activity relationships were discussed.
Keywords:3-Azabicyclo-nonanes  2-Azabicyclo-nonanes  Bicyclo-octanes
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