WebPrevious prodrugs of 2 aimed at improving solubility by incorporating enzymatically labile amino acid and phosphate ester promoieties. These approaches were effective but led to limitations with in vivo administration. Herein, we disclose a pH-responsive water-soluble prodrug strategy to improve exposure to 2 through enzyme-independent activation. WebApr 12, 2024 · Organophosphorus compounds have found widespread applications in pharmaceuticals, agrochemicals, and materials science. Phosphonates, in particular, can be regarded as isosteres of the corresponding phosphate esters and serve as phosphate mimics in biochemical investigations. 1 The introduction of a phosphonic acid of suitable …

Phosphate Ester Prodrugs - Prodrugs - European Medical

WebPhosphate ester prodrugs of propofol (fospropofol, HX0969W) were designed to avoid the unsatisfactory water solubility of the parent drug. However, in previous clinical trials, there … WebAug 21, 2014 · 3′,5′-Cyclic phosphate ester prodrugs (Figure 26) are part of an interesting prodrug concept that led to the discovery of PSI-352938, a compound that demonstrated anti-HCV efficacy in vitro and in human phase 1 trials. The activation of these derivatives to the monophosphate involves, first, an enzymatic P–O-dealkylation by CYP3A4 and ... greatest food of all time

Synthesis and Biological Evaluation of Phosphate Prodrugs of …

WebPhosphate ester prodrugs substantially enhance the aqueous solubility of some poorly soluble parent drugs due to ionization of the phosphate group at physiological pH. While phosphate prodrugs have proven successful in parenteral formulations, few oral phosphate prodrugs have been marketed to date as they have generally failed to improve parent ... WebProdrugs of phosphonates and phosphates: crossing the membrane barrier A substantial portion of metabolism involves transformation of phosphate esters, including pathways … Web3. Phosphate Esters as Prodrugs of Hydroxyl or Amine Functionalities Phosphate ester prodrugs are typically designed for hydroxyl and amine functionalities of poorly water-soluble drugs with an aim to enhance their aqueous solubility to allow a more favorable oral or parenteral administration (see examples in Table 2). greatest food in the world