Syntheses and antimalarial activities of N-substituted 11-azaartemisinins

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

Research output: Contribution to journalArticle

63 Citations (Scopus)

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
StatePublished - 1995

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Antimalarials
Ammonia
Silica Gel
Plasmodium falciparum
Metabolites
Amines
Derivatives
Pharmaceutical Preparations
artemisinine
amberlyst-15
In Vitro Techniques

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Torok, D. S., Ziffer, H., Meshnick, S. R., Pan, X. Q., & Ager, A. L. (1995). Syntheses and antimalarial activities of N-substituted 11-azaartemisinins. Journal of Medicinal Chemistry, 38(26), 5045-5050.

Syntheses and antimalarial activities of N-substituted 11-azaartemisinins. / Torok, Daniel S.; Ziffer, Herman; Meshnick, Steven R.; Pan, Xing Qing; Ager, Arba L.

In: Journal of Medicinal Chemistry, Vol. 38, No. 26, 1995, p. 5045-5050.

Research output: Contribution to journalArticle

Torok, DS, Ziffer, H, Meshnick, SR, Pan, XQ & Ager, AL 1995, 'Syntheses and antimalarial activities of N-substituted 11-azaartemisinins', Journal of Medicinal Chemistry, vol. 38, no. 26, pp. 5045-5050.
Torok DS, Ziffer H, Meshnick SR, Pan XQ, Ager AL. Syntheses and antimalarial activities of N-substituted 11-azaartemisinins. Journal of Medicinal Chemistry. 1995;38(26):5045-5050.
Torok, Daniel S. ; Ziffer, Herman ; Meshnick, Steven R. ; Pan, Xing Qing ; Ager, Arba L. / Syntheses and antimalarial activities of N-substituted 11-azaartemisinins. In: Journal of Medicinal Chemistry. 1995 ; Vol. 38, No. 26. pp. 5045-5050.
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