Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin.
A series of N-substituted 11-azaartemisinins were prepared in high yield employing base-catalyzed additions to an amide nitrogen of olefins and terminal acetylenes conjugated with electron withdrawing groups (EWGs). When the terminal acetylene was conjugated with carbomethoxy, N,N-dimethyl amide or carbonyl groups, the E-adducts resulted. A mixture of E- and Z-adducts were obtained when the EWG was a nitrile. In vitro antimalarial activities of each compound were determined against two drug-resistant strains of Plasmodium falciparum. Many of the compounds prepared were several times more active than artemisinin.
Mekonnen
B
B
NIMH, Laboratory of Neurotoxicology, Bethesda, MD 20892-5100, USA.
Weiss
E
E
Katz
E
E
Ma
J
J
Ziffer
H
H
Kyle
D E
DE
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy; D010963:Plasmodium falciparum / Q000187:drug effects*; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology
D000962:Antimalarials; D001372:Aza Compounds; D012717:Sesquiterpenes