Singh Chandan, Malik Heetika, Puri Sunil K
Division of Medicinal & Process Chemistry, Central Drug Research Institute, Lucknow-226001, India.
J Med Chem. 2006 May 4;49(9):2794-803. doi: 10.1021/jm051130r.
Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days by oral route. Trioxanes 10, 12, 14, 16, 18, 20, and 22 have shown promising antimalarial activity. Trioxanes 14 and 18, the two most active compounds of the series, provide 100% and 60% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively. In this model beta-arteether provides 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively.
以易于获取的酮三恶烷7a - g为起始原料，制备了一系列新型的、具有不同官能团化的1,2,4 - 三恶烷10 - 36，并通过口服途径在24 mg/kg×4天至96 mg/kg×4天的剂量范围内对其抗多重耐药约氏疟原虫（Plasmodium yoelii nigeriensis）的小鼠抗疟活性进行了评估。三恶烷10、12、14、16、18、20和22表现出了有前景的抗疟活性。该系列中活性最强的两种化合物三恶烷14和18，在48 mg/kg×4天和24 mg/kg×4天的剂量下分别提供了100%和60%的保护作用。在此模型中，蒿甲醚在48 mg/kg×4天和24 mg/kg×4天的剂量下分别提供了100%和20%的保护作用。
