Synthesis and Antimalarial Activity of 3,3-Spiroanellated 5,6-Disubstituted 1,2,4-Trioxanes

被引：21

作者：

Maurya, Ranjani ^{[1
]}

Soni, Awakash ^{[2
]}

Anand, Devireddy ^{[1
]}

Ravi, Makthala ^{[1
]}

Raju, Kanumuri S. R. ^{[3
]}

Taneja, Isha ^{[3
]}

Naikade, Niraj K. ^{[1
]}

Puri, S. K. ^{[2
]}

Wahajuddin ^{[3
]}

Kanojiya, Sanjeev ^{[4
]}

Yadav, Prem P. ^{[1
]}

机构：

[1] Cent Drug Res Inst, Div Med & Proc Chem, Lucknow 226001, Uttar Pradesh, India

[2] Cent Drug Res Inst, Div Parasitol, Lucknow 226001, Uttar Pradesh, India

[3] Cent Drug Res Inst, Div Pharmacokinet & Metab, Lucknow 226001, Uttar Pradesh, India

[4] Cent Drug Res Inst, Sophisticated Analyt Instrument Facil, Lucknow 226001, Uttar Pradesh, India

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2013年 / 4卷 / 02期

关键词：

1,2,4-trioxane; antimalarial; in vivo; orally active; CHLOROQUINE-RESISTANT PARASITES; RODENT MALARIA; QINGHAOSU ARTEMISININ; PLASMODIUM-BERGHEI; ALLYLIC ALCOHOLS; DRUG; CHEMOTHERAPY; PEROXIDES; CHEMISTRY; YOELII;

D O I：

10.1021/ml300188t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 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 x 4 days to 24 mg/kg x 4 days. The most active compound of the series (compound 25) provided 100% protection at 24 mg/kg x 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. In this model, beta-arteether provided 100 and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively, by oral route. Compound 25 displayed a similar in vitro pharmacokinetic profile to that of reference drug beta-arteether. The activity results demonstrated the importance of an aryl moiety at the C-5 position on the 1,2,4-trioxane pharmacophore.

引用

页码：165 / 169

页数：5

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