Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin

McGuigan, Christopher; Thiery, Jean-Christophe; Daverio, Felice; Jiang, Wen Guo; Davies, Gaynor; Mason, Malcolm David

doi:10.1016/j.bmc.2005.02.041

Cited by 53 publications

(35 citation statements)

References 16 publications

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“…The mechanism of activation of aryl phosorphoramidate prodrugs is established [21–25] and the scheme is adapted from [21,37]. The first step is enzymatic and occurs by the hydrolysis of either of the two esters (R1 and R2) carried out by cellular carboxylesterases.…”

Section: Figmentioning

confidence: 99%

Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy

Zano

Pate

Frank

et al. 2015

Molecular Genetics and Metabolism

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Coenzyme A (CoA) is a ubiquitous cofactor involved in numerous essential biochemical transformations, and along with its thioesters is a key regulator of intermediary metabolism. Pantothenate (vitamin B5) phosphorylation by pantothenate kinase (PanK) is thought to control the rate of CoA production. Pantothenate kinase associated neurodegeneration is a hereditary disease that arises from mutations that inactivate the human PANK2 gene. Aryl phosphoramidate phosphopantothenate derivatives were prepared to test the feasibility of using phosphopantothenate replacement therapy to bypass the genetic deficiency in the Pank1−/− mouse model. The efficacies of candidate compounds were first compared by measuring the ability to increase CoA levels in Pank1−/− mouse embryo fibroblasts. Administration of selected candidate compounds to Pank1−/− mice corrected their deficiency in hepatic CoA. The PanK bypass was confirmed by the incorporation of intact phosphopantothenate into CoA using tripleisotopically labeled compound. These results provide strong support for PanK as a master regulator of intracellular CoA and illustrate the feasibility of employing PanK bypass therapy to restore CoA levels in genetically deficient mice.

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Section: Figmentioning

confidence: 99%

Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy

Zano

Pate

Frank

et al. 2015

Molecular Genetics and Metabolism

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“…However, reaction of DAPD 1 with phosphoramidate chloride 6 7 in the presence of t -BuMgCl afforded DAPD prodrug 5 in only 45% yield (Scheme 1). To further complicate this approach, acylation reactions with 5 would either proceed to only about 50% or when forced gave a substantial amount of the N 2 , N 6 -diacylated product.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and antiviral evaluation of 2-amino-6-carbamoylpurine dioxolane nucleoside derivatives and their phosphoramidates prodrugs

Cho

Bondana

Detorio

et al. 2014

Bioorganic & Medicinal Chemistry

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“…[8] The prodrug strategy was based on the phosphoramidate approach developed by McGuigan and co-workers. [9,10] …”

Section: Synthesis and Biological Evaluation Of Lna Phosphoramidatesmentioning

confidence: 98%

Synthesis and Biological Evaluation of LNA Phosphoramidates

Jensen¹,

Sjøgren²,

Hansen³

et al. 2008

Nucleosides, Nucleotides and Nucleic Acids

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Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin

Cited by 53 publications

References 16 publications

Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy

Correction of a genetic deficiency in pantothenate kinase 1 using phosphopantothenate replacement therapy

Synthesis and antiviral evaluation of 2-amino-6-carbamoylpurine dioxolane nucleoside derivatives and their phosphoramidates prodrugs

Synthesis and Biological Evaluation of LNA Phosphoramidates

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