Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials1
详细信息 查看全文
- 作者：Igor Opsenica ; Dejan Opsenica ; Kirsten S. Smith ; Wilbur K. Milhous ; Bogdan A. Š ; olaja
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：April 10, 2008
- 年：2008
- 卷：51
- 期：7
- 页码：2261 - 2266
- 全文大小：106K
- 年卷期：v.51,no.7(April 10, 2008)
- ISSN：1520-4804
文摘
Of 17 prepared 1,2,4,5-tetraoxacyclohexanes stable to reductive and acidic conditions, 3 of them were more active than artemisinin against CQ and MFQ resistant strain TM91C235 and all compounds were more active in vitro against W2 than against D6 strain. In vivo, amines 10 and 11a cured all mice at higher doses with MCD ≤ 37.5 (mg/kg)/day. Triol 13 was exceptionally active against melanoma (LOX IMVI) and ovarian cancer (IGROV1), both with LC50 = 60 nM.