STRUCTURE-ACTIVITY-RELATIONSHIPS OF THE ANTIMALARIAL AGENT ARTEMISININ .2. EFFECT OF HETEROATOM SUBSTITUTION AT O-11 - SYNTHESIS AND BIOASSAY OF N-ALKYL-11-AZA-9-DESMETHYLARTEMISININS

A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemi sinins 17-29, were synthesized via ozonolysis and acid-catalyzed cycli zation of precursor amides 5-16. These amides were prepared through co ndensation of an activated ester of the known intermediate acid 2 with the, corresponding primary amine. The analogs were tested in vitro ag ainst W-2 and D-6 strains of Plasmodium falciparum and found in some c ases to be more active than artemisinin. A comparison of the in vitro testing methods of Milhous and Makler was conducted and gave similar r elative antimalarial activities for these artemisinin analogs. Log P v alues were determined for most of the compounds, but no apparent corre lation between log P and in vitro activity was found.