Efficient Strategy to Prepare Water-Soluble Prodrugs of Ketones

Huttunen, Kristiina M.; Kumpulainen, Hanna; Leppänen, Jukka; Rautio, Jarkko; Järvinen, Tomi; Vepsäläinen, Jouko

doi:10.1055/s-2006-933115

Cited by 4 publications

(2 citation statements)

References 4 publications

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“…A series of oxime derivatives were prepared from 24 in order to add diversity to this chemical series and to probe SAR. The oxime functionality was desirable because it is already contained in known drugs and has shown activity against protozoa , and evidence suggests that it is a suitable “water-soluble prodrug” that might unveil the ketone under biological conditions. − The initial series of analogues, prepared by treating 24 with the appropriate commercially available hydroxylamine in pyridine, consisted of the parent oxime ( 25 ), the O -methyloxime ( 26 ), and the O -allyloxime ( 27 , Scheme a). Analogues containing bulkier alkyl groups were also prepared and included cyclopropylmethylene oxime ( 28 ), isobutyloxime ( 29 ), and tert -butyloxime ( 30 ).…”

Section: Analogue Synthesismentioning

confidence: 99%

Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs

et al. 2013

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Malaria continues to be a difficult disease to eradicate, largely due to the widespread populations it affects and to the resistance that malaria parasites have developed against once very potent therapies. The natural product artemisinin has been a boon for antimalarial chemotherapy as artemisinin combination therapy (ACT) has become the first line of chemotherapy. Because the threat of resistance is always on the horizon, it is imperative to continually identify new treatments, comprised of both advanced analogs of all antimalarial drugs, especially artemisinin, as well as the exploration of novel combinations, ideally with distinct mechanisms of action. Here we report, for the first time, synthesis of a series of two-carbon linked artemisinin-derived dimers, their unique structural features, and demonstration of their antimalarial efficacy via single oral dose administration in two 60-day survival studies of Plasmodium berghei-infected mice. Several of the new endoperoxide chemical entities consistently demonstrated excellent antimalarial efficacy, and combinations with two non-peroxide antimalarial drugs have been studied.

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Section: Analogue Synthesismentioning

confidence: 99%

Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs

et al. 2013

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“…4 Recently a study of ketoxime phosphates using as phosphate prodrug structures has been reported. 5 Therefore the development of a facile and efficient method for synthesis of the oxime phosphates is required.…”

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confidence: 99%

The Mild Synthesis of Oxime Phosphates by Atherton–Todd Reaction

Zhang

2007

Journal of Chemical Research

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Phosphorus Derivatives of Hydroxylamines, Oximes and Hydroxamic Acids

Palácios

Santos

Vicario

et al. 2010

Patai's Chemistry of Functional Groups

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This comprehensive chapter, organized in three different sections, includes new topics focused on preparation and synthetic applications of phosphorus functionalized hydroxylamines, oximes and hydroxamic acids. The first section comprises the synthesis of phosphorus O ‐substituted hydroxylamines either through phosphorus‐oxygen or nitrogen‐oxygen single bond formation. The synthesis of N ‐substituted hydroxylamines is also covered in this first section by means of phosphorus‐nitrogen or carbon‐nitrogen bond formation reactions. This section also includes several transformations of phosphorus substituted hydroxylamines including among others: rearrangement, hydrolysis, reduction and oxidation reactions. Functionalized oximes containing phosphorus substituents including O ‐ and C ‐substituted oximes, and oximes with α‐ and β‐phosphorated moieties are covered in a second section. This provides an introduction to the common approaches to synthesize phosphorus substituted oximes, and the application of phosphorated oximes to the preparation of more elaborated compounds have been described. Some of the synthetic applications methods covered in the second section are fragmentation and rearrangement reactions, nucleophilic substitution at the phosphorus atom, intramolecular reactions, radical reactions, reduction of carbon‐nitrogen double bond, oxidation reactions, olefination reactions, dehydratation of oximes. The third section is dedicated to the synthesis and reactivity of phosphorus O ‐, N ‐, and C ‐substituted hydroxamic acid derivatives, spanning the few reports in the literature covering this topic. An extensive and current list of references and a subject index complete the chapter. Phosphorus Substituted Hydroxylamine Derivatives Phosphorus Substituted Oximes Phosphorus Substituted Hydroxamic Acid Derivatives Acknowledgments

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Efficient Strategy to Prepare Water-Soluble Prodrugs of Ketones

Cited by 4 publications

References 4 publications

Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs

Synthesis and Antimalarial Efficacy of Two-Carbon-Linked, Artemisinin-Derived Trioxane Dimers in Combination with Known Antimalarial Drugs

The Mild Synthesis of Oxime Phosphates by Atherton–Todd Reaction

Phosphorus Derivatives of Hydroxylamines, Oximes and Hydroxamic Acids

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