Kinetic Studies of the Degradation of Oxycarbonyloxymethyl Prodrug of Adefovir and Tenofovir in Solution

Abstract

The decomposition kinetics of bis-POC PMEA and bis-POC PMPA followed pseudo-first order kinetics with the corresponding mono-POC ester detected as the only observable degradation product for all the pH values studied. The rates of hydrolysis of bis-POC PMEA over the pH range studied was described by [formula: see text] The 18O incorporation studies revealed that hydrolysis of bis-POC PMEA at pH 7.0 primarily proceeds via P-O cleavage with an additional minor pathway involving C-O bond cleavage. Hydrolysis of bis-POC PMPA was found to be about 2 fold slower than bis-POC PMEA at pH values above 6.0.

Griffithsin, a potent HIV entry inhibitor, is an excellent candidate for anti‐HIV microbicide

“…Our study evaluated only the irreversible effects on efficacy induced by pH or CVL, and would not detect transient or reversible effects. For example, bis(POC)PMPA undergoes spontaneous hydrolysis and degradation in alkaline pH [13, 25], and this irreversible degradation may result in loss of anti‐HIV efficacy. In addition, CVN undergoes reversible conversion between monomeric or dimeric structures at low or neutral pH, but this switch has little effect on antiviral potency [2, 3, 27].…”

Evaluation of the fusion inhibitor P3 peptide as a potential microbicide to prevent HIV transmission in women

“…Remarkably, at pH = 4 which is the pH of the healthy vagina, the anti-HIV-1 activity of P3 was even better than at more alkaline pH. Bacterial vaginosis is a human vaginal infection in which the vaginal pH is increased towards alkaline values (pH>4.5) [ 50 ]; such pH changes may contribute for spontaneous hydrolysis and degradation of anti-HIV compounds [ 51 ]. In our case the antiviral activity of P3 was not affected at pH 6 and 8.…”

The Shortest Strategy for Generating Phosphonate Prodrugs by Olefin Cross‐Metathesis – Application to Acyclonucleoside Phosphonates

“…Flash column chromatography was performed on silica gel 60 (230-400 mesh). The compounds were characterized by 1 H, 13 C, and 31 P NMR (Supporting Information). HRMS was conducted using the ESI technique.…”

“…[30] Furthermore, acyloxyalkyl ester phosphonates such as POC are unstable due to the possible nucleophilic attack of water at the carbonyl center and phosphorus atom at 37°C and pH 7. [31] On the basis of these considerations, which could hamper CM efficiency, we hypothesized that CM reactions could be Ru-catalyst dependant. The evaluation of the catalytic efficiency of eight Ru catalysts (1a, 1b, 1d, and 3a-e), including the Ru-indenylidene catalyst that bears SIPr (3e), for the CM reaction between our phosphonate synthons (4, 5, and 13) and N 1 -crotylated-C 5 -substituted uracils, which were chosen as representative of the class of therapeutic molecules.…”