2753-41-5Relevant academic research and scientific papers
Membrane Permeable, Bioreversibly Modified Prodrugs of Nucleoside Diphosphate-γ-Phosphonates
Jia, Xiao,Weber, Stefan,Schols, Dominique,Meier, Chris
, p. 11990 - 12007 (2020)
Nucleoside reverse transcriptase inhibitors (NRTIs) are widely used as antiviral and anticancer agents, although they require intracellular phosphorylation into their antivirally active form, the triphosphorylated nucleoside analogue metabolites. We report on the synthesis and characterization of a new class of nucleoside triphosphate analogues comprising a C-alkyl-phosphonate moiety replacing the γ-phosphate. These compounds were converted into bioreversibly modified lipophilic prodrugs at the γ-phosphonate by the attachment of an acyloxybenzyl (ester) or an alkoxycarbonyloxybenzyl (carbonate) group. Such compounds formed γ-C-(alkyl)-nucleoside triphosphate analogues with high selectivity because of an enzyme-triggered delivery mechanism. The latter compounds were very stable in CD4+ T-lymphocyte (CEM cell) extracts, and they were substrates for HIV-reverse transcriptase without being substrates for DNA-polymerases α, β, and γ. In antiviral assays, the excellent antiviral activity of the prodrugs that was found in CEM/0 cells was completely kept in CEM/TK- cells. The activity was improved by 3 logs as compared to the parent nucleoside d4T.
Chemoselective synthesis of long-chain alkyl-H-phosphinic acidsviaone-pot alkylation/oxidation of red phosphorus with alkyl-PEGs as recyclable micellar catalysts
Belogorlova, Natalia A.,Gusarova, Nina K.,Kuimov, Vladimir A.,Malysheva, Svetlana F.,Trofimov, Boris A.
, p. 10587 - 10595 (2021/12/27)
Long-chainn-alkyl-H-phosphinic acids (Alk = C4-C18) are chemoselectively synthesized in yields up to 90%viathe direct one-pot alkylation/oxidation of red phosphorus (Pn) in the multi-phase alkyl bromide/KOH/H2O/
Synthesis of a phosphinate analogue of the anti-tumour phosphate di-ester perifosine via sequential radical processes
Markoulides, Marios S.,Regan, Andrew C.
, p. 119 - 129 (2013/02/23)
An efficient synthesis of a phosphinate analogue of the anti-tumour phosphate di-ester perifosine is described (6 steps and 50% overall yield). The two phosphorus-carbon bonds in the perifosine analogue were prepared by sequential double radical hydrophosphinylation processes. This is the first example of a phosphinate analogue of perifosine, designed to be resistant to hydrolysis by phospholipid-metabolizing enzymes. The Royal Society of Chemistry.
