Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; synthetic antimalarials with superior activity to artemisinin

被引：80

作者：

Amewu, Richard

Stachulski, Andrew V.

Ward, Stephen A.

Berry, Neil G.

Bray, Patrick G.

Davies, Jill

Labat, Gael

Vivas, Livia

O'Neill, Paul M.

机构：

[1] Univ Liverpool, Dept Chem, Liverpool L69 3BX, Merseyside, England

[2] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England

[3] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2006年 / 4卷 / 24期

关键词：

D O I：

10.1039/b613565j

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Unsymmetrical dispiro- and spirotetraoxanes have been designed and synthesized via acid-catalyzed cyclocondensation of bis(hydroperoxides) with ketones. Incorporation of water-soluble and polar functionalities, via reductive amination and amide bond formation, produces several analogues with low nanomolar in vitro antimalarial activity. Several analogues display an unprecedented level of oral antimalarial activity for this class of endoperoxide drug.

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页码：4431 / 4436

页数：6

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