Synthesis and Antimalarial Activity of 3,3-Spiroanellated 5,6-Disubstituted 1,2,4-Trioxanes
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- 作者：Ranjani Maurya ; Awakash Soni ; Devireddy Anand ; Makthala Ravi ; Kanumuri S. R. Raju ; Isha Taneja ; Niraj K. Naikade ; S. K. Puri ; Wahajuddin ; Sanjeev Kanojiya ; Prem P. Yadav
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2013
- 出版时间：February 14, 2013
- 年：2013
- 卷：4
- 期：2
- 页码：165-169
- 全文大小：295K
- 年卷期：v.4,no.2(February 14, 2013)
- ISSN：1948-5875
文摘
Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19鈥?b>34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg 脳 4 days to 24 mg/kg 脳 4 days. The most active compound of the series (compound 25) provided 100% protection at 24 mg/kg 脳 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. In this model, 尾-arteether provided 100 and 20% protection at 48 mg/kg 脳 4 days and 24 mg/kg 脳 4 days, respectively, by oral route. Compound 25 displayed a similar in vitro pharmacokinetic profile to that of reference drug 尾-arteether. The activity results demonstrated the importance of an aryl moiety at the C-5 position on the 1,2,4-trioxane pharmacophore.