Synthesis and Antimalarial Assessment of a New Series of Orally Active Amino-Functionalized Spiro 1,2,4-Trioxanes
作者:Chandan Singh、Mohammad Hassam、Niraj Krishna Naikade、Ved Prakash Verma、Ajit Shankar Singh、Sunil. K. Puri
DOI:10.1021/jm100678p
日期:2010.11.11
Keto-trioxanes 7a−d, easily accessible in two steps from allylic alcohols 5a−d, underwent reductive amination with substituted anilines to furnish amino-functionalized trioxanes 8a−i, 9a−i, 10a−i, and 11a−i. All these new trioxanes were assessed for their oral antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice. 2-Naphthalene-based trioxanes 9c and 9i, the
从烯丙基醇5a - d可以很容易地分两步获得酮基-三恶烷7a - d,并用取代的苯胺进行还原胺化,以提供氨基官能化的三恶烷8a - i,9a - i,10a - i和11a - i。对所有这些新的三恶烷在瑞士小鼠中针对多药耐药性约氏疟原虫的口服抗疟活性进行了评估。2-萘基三恶烷9c和9i,该系列中活性最高的化合物以24 mg / kg×4天的时间为感染疟疾的小鼠提供100%的保护,而相关的三恶烷9b和菲基三恶烷11e的保护水平为48 mg / kg ×4天。除10c,10d和10g外,所有其他三恶烷在96 mg / kg×4天时提供100%的保护。在该模型中,β-蒿甲醚在48 mg / kg×4天时提供100%的保护,在24 mg / kg×4天时提供20%的保护。