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

Richard Amewu; Andrew V. Stachulski; Steve Ward; Neil G. Berry; Patrick G. Bray; Jill Davies; Gael Labat; Livia Vivas; Paul M. O'Neill

doi:10.1039/b613565j

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

Richard Amewu, Andrew V. Stachulski, Steve Ward, Neil G. Berry, Patrick G. Bray, Jill Davies, Gael Labat, Livia Vivas, Paul M. O'Neill

Tropical Disease Biology

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	4431-4436
Number of pages	6
Journal	Organic and Biomolecular Chemistry
Volume	4
Issue number	24
DOIs	https://doi.org/10.1039/b613565j
Publication status	Published - 1 Dec 2006

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10.1039/b613565j

89 Citations
1 Other contribution

Erratum: Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; Synthetic antimalarials with superior activity to artemisinin
Amewu, R., Stachulski, A. V., Ward, S., Berry, N. G., Bray, P. G., Davies, J., Labat, G., Vivas, L. & O'Neill, P. M., 1 Jan 2007, 1 p.
Research output: Other contribution

Open Access

2 Citations (Scopus)

Cite this

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

abstract = "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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AU - Amewu, Richard

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AU - Ward, Steve

AU - Berry, Neil G.

AU - Bray, Patrick G.

AU - Davies, Jill

AU - Labat, Gael

AU - Vivas, Livia

AU - O'Neill, Paul M.

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AB - 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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DO - 10.1039/b613565j

M3 - Article

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JF - Organic and Biomolecular Chemistry

IS - 24

ER -

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

Abstract

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Research output

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

Cite this