O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin

Meier, Chris; Neumann, Jean‐Michel; André, François; Hénin, Y.; Tam, Huynh Dinh

doi:10.1021/jo00052a053

Cited by 38 publications

(25 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The HIV-1-induced cytopathic effect (CPE) was monitored by the MTT viability assay to determine EC 50MTT and CC 50 as previously described. 15 HIV replication was also followed by measurement of the reverse transcriptase activity in the culture supernatant (EC 50RT ). The results obtained are shown in Table 3.…”

Section: Biological Results and Discussionmentioning

confidence: 99%

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

et al. 1997

View full text Add to dashboard Cite

A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045-0.082 microM range. The analogs 12d, 12e, 12q, 15, and 19 were active at <0.5 microM concentration. Compound 18 in which two molecules of AZT are connected at N-3 via a two-carbon link and "dimer" 11 also displayed significant activity. To obtain information concerning the mechanism of RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT(12-18)] and poly(C)-oligo[dG(12-18)] template-primers. In contrast to AZT-TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequisite for activity.

show abstract

Section: Biological Results and Discussionmentioning

confidence: 99%

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

et al. 1997

View full text Add to dashboard Cite

show abstract

“…2 Acyl nucleotide 3 derivatives of d4T and AZT, as well as O-alkyl-5',5'-dinucleoside phosphates of AZT/cordycepin 4 have been synthesized. Generally, the anti-HIV efficacy of the prodrug was lower 3,4 or similar 3 than that of the parent nucleotide. Many more phosphodiester prodrugs of modified nucleosides have been studied 5 but generally it is believed that mono alkyl/aryl phosphodiesters are unsuitable for the intracellular delivery of nucleotides.…”

mentioning

confidence: 95%

Hydroxy fatty acids for the delivery of dideoxynucleosides as anti-HIV agents

Gangadhara

Lescrinier

Pannecouque

et al. 2014

Bioorganic & Medicinal Chemistry Letters

View full text Add to dashboard Cite

Starting from thymidine, through a series of key synthetic transformations (e.g. Wittig reaction, hydroboration, Mitsunobu reaction and TEMPO oxidation) a nucleoside homologue bearing a phospho-carboxylic anhydride group at 6' position was synthesized. The potential of polymerases to catalyze amide bond formation was investigated by using a modified primer with an amino group at 3' position and the synthesized phosphoanhydro compound as substrate. Unfortunately, we did not observe the desired product either by gel electrophoresis or mass spectrometry. In contrast, the instability of the phosphoanhydro compound could lead to pyrophosphate formation and thus, to pyrophosphorolysis of the primer rather than to primer extension. Graphical Abstract O OH HO N NH O O O N 3 N NH O O O P HO O O OH In coeval life, proteins and nucleic acids are intricately dependent upon each other for a host of functions. Protein enzymes (polymerases) are necessary for the synthesis of DNA and RNA, while nucleic acids (ribosomes) are necessary for the synthesis of proteins. According to the RNA world hypothesis, early life used nucleic acids for both information storage and chemical catalysis before the emergence of protein enzymes. However, it still remains unclear how nucleic acids were able to assemble and replicate before the advent of protein enzymes. This means that in contemporary life, proteins can catalyze phosphodiester bond formation (nucleic acid synthesis) and nucleic acids can catalyze amide bond formation (protein synthesis). Our motivation in this context comes from the recently proposed 'Molecular Midwife' hypothesis 1 and has the aim to investigate if

show abstract

“…The phosphoric triester linkage in oligonucleotides can be constructed by oxidative substitution of dinucleoside H-phosphonates with an alcohol (6), transesterification of dinucleoside phosphoric triesters (7), or alkylation of dinucleoside phosphoric diesters. As an example of the latter, two 0-alkyl-5,5'-dinucleoside phosphates have been synthesized as potential anti-AIDS reagents (8).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and separation of diastereomers of O-(2,2,2-trifluoroethyl)-3′,5′-dinucleoside phosphates

Luo¹,

Atrazheva²,

Fregeau³

et al. 1994

Can. J. Chem.

View full text Add to dashboard Cite

The synthesis, diastereomeric separation, and characterization are described for a series of novel O-(2,2,2-trifluoroethyl)-3′,5′-dinucleoside phosphates, required for incorporation into antisense probes in the magnetic resonance imaging investigation of biodistribution. Preliminary assignment of the absolute configuration of the Rp and Sp diastereomers is made on the basis of 31 P NMR spectra.

show abstract

O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin

Cited by 38 publications

References 0 publications

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs

Hydroxy fatty acids for the delivery of dideoxynucleosides as anti-HIV agents

Synthesis and separation of diastereomers of O-(2,2,2-trifluoroethyl)-3′,5′-dinucleoside phosphates

Contact Info

Product

Resources

About