Antimalarial simplified 3-aryltrioxanes: Synthesis and preclinical efficacy/toxicity testing in rodents

G. H. Posner; Bae Jeon Heung Bae Jeon; M. H. Parker; M. Krasavin; I. H. Paik; T. A. Shapiro

doi:10.1021/jm0102396

Antimalarial simplified 3-aryltrioxanes: Synthesis and preclinical efficacy/toxicity testing in rodents

G. H. Posner, Bae Jeon Heung Bae Jeon, M. H. Parker, M. Krasavin, I. H. Paik, T. A. Shapiro

School of Medicine

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

60 Scopus citations

Abstract

A streamlined five-step chemical synthesis of rationally designed, simplified 3-aryltrioxane 8a is described. A noteworthy feature of this synthetic scheme is use of air rather than expensive molecular oxygen as the source of the pharmacologically critical peroxide unit in trioxane 8a. This simplified acetal trioxane carboxylic acid 8a is thermally stable, and it is hydrolytically stable in water even at 40 °C and pH 7.4 for at least 7 days. Preclinical evaluation of this water-soluble synthetic trioxane 8a in rodents shows it to have at least as good a therapeutic index (efficacy/toxicity) as that of water-soluble semisynthetic trioxane artelinic acid (5).

Original language	English (US)
Pages (from-to)	3054-3058
Number of pages	5
Journal	Journal of medicinal chemistry
Volume	44
Issue number	19
DOIs	https://doi.org/10.1021/jm0102396
State	Published - Sep 13 2001

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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abstract = "A streamlined five-step chemical synthesis of rationally designed, simplified 3-aryltrioxane 8a is described. A noteworthy feature of this synthetic scheme is use of air rather than expensive molecular oxygen as the source of the pharmacologically critical peroxide unit in trioxane 8a. This simplified acetal trioxane carboxylic acid 8a is thermally stable, and it is hydrolytically stable in water even at 40 °C and pH 7.4 for at least 7 days. Preclinical evaluation of this water-soluble synthetic trioxane 8a in rodents shows it to have at least as good a therapeutic index (efficacy/toxicity) as that of water-soluble semisynthetic trioxane artelinic acid (5).",

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AU - Posner, G. H.

AU - Heung Bae Jeon, Bae Jeon

AU - Parker, M. H.

AU - Krasavin, M.

AU - Paik, I. H.

AU - Shapiro, T. A.

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Antimalarial simplified 3-aryltrioxanes: Synthesis and preclinical efficacy/toxicity testing in rodents

Abstract

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