Zhao, Chenglong; Weber, Stefan; Schols, Dominique; Balzarini, Jan; Meier, Chris published the artcile< Prodrugs of γ-Alkyl-Modified Nucleoside Triphosphates: Improved Inhibition of HIV Reverse Transcriptase>, Related Products of 112-63-0, the main research area is nucleoside triphosphate prodrug HIV reverse transcriptase human; DNA polymerases; antiviral agents; biological activity; nucleoside triphosphates; prodrugs.
The development of nucleoside triphosphate prodrugs is one option to apply nucleoside reverse transcriptase inhibitors. Herein, we report the synthesis and evaluation of d4TTP analogs, in which the γ-phosphate was modified covalently by lipophilic alkyl residues, and acyloxybenzyl prodrugs of these γ-alkyl-modified d4TTPs, with the aim of delivering of γ-alkyl-d4TTP into cells. Selective formation of γ-alkyl-d4TTP was proven with esterase and in CD4+-cell extracts In contrast to d4TTP, γ-alkyl-d4TTPs proved highly stable against de-phosphorylation. Primer extension assays with HIV reverse transcriptase (RT) and DNA-polymerases α, β or γ showed that γ-alkyl-d4TTPs were substrates for HIV-RT only. In antiviral assays, compounds were highly potent inhibitors of HIV-1 and HIV-2 also in thymidine-kinase-deficient T-cell cultures (CEM/TK-). Thus, the intracellular delivery of such γ-alkyl-nucleoside triphosphates may potentially lead to nucleoside triphosphates with a higher selectivity towards the viral polymerase that can act in virus-infected cells.
Angewandte Chemie, International Edition published new progress about AIDS (disease). 112-63-0 belongs to class esters-buliding-blocks, and the molecular formula is C19H34O2, Related Products of 112-63-0.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics