title: Synthesis and antimalarial activities of base-catalyzed adducts of 11-azaartemisinin.
abstract: 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.
authors.affiliation: NIMH, Laboratory of Neurotoxicology, Bethesda, MD 20892-5100, USA.
authors.forename: B
authors.initials: B
authors.lastname: Mekonnen
authors.forename: E
authors.initials: E
authors.lastname: Weiss
authors.forename: E
authors.initials: E
authors.lastname: Katz
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: H
authors.initials: H
authors.lastname: Ziffer
authors.forename: D E
authors.initials: DE
authors.lastname: Kyle
mesh_terms: 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
chemical_list: D000962:Antimalarials; D001372:Aza Compounds; D012717:Sesquiterpenes