Syntheses and Antimalarial Activities of N-Substituted 11-Azaartemisinins

Daniel S. Torok, Herman Ziffer, Steven R. Meshnick, Xing Qing Pan, Arba Ager

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11-azaartemisinin in 65% yield. Substituting a variety of primary alkyl- and heteroaromatic amines for ammonia in the reaction sequence yields N-substituted 11-azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11-azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are formed in 45% and 15% yields, respectively. In vitro and in vivo test data for a number of novel N-substituted 11-azaartemisinins, against drug-resistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2′-acetaldehydo)-11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin.

Original languageEnglish (US)
Pages (from-to)5045-5050
Number of pages6
JournalJournal of Medicinal Chemistry
Volume38
Issue number26
DOIs
StatePublished - Dec 1 1995

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Torok, D. S., Ziffer, H., Meshnick, S. R., Pan, X. Q., & Ager, A. (1995). Syntheses and Antimalarial Activities of N-Substituted 11-Azaartemisinins. Journal of Medicinal Chemistry, 38(26), 5045-5050. https://doi.org/10.1021/jm00026a012