Phosphate ester prodrug

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August undefined, 2024

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. WebPhosphonates, phosphinates, and phosphates are prominently represented as pharmacophores in various classes of biological agents. These include antiviral and anticancer nucleotides, inhibitors of biosynthesis of cholesterol, angiotensin-converting enzyme inhibitors, and bisphosphonates for the treatment of osteoporosis.

The expanding role of prodrugs in contemporary drug design and …

WebApr 12, 2024 · The phosphate prodrug of dexamethasone has a very short half-life of just over 5 min, and it could not be detected in the plasma of healthy volunteers after 30 min [ … 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). north bethesda maryland wikipedia

Prodrugs of biologically active phosphate esters

WebMar 20, 2003 · This approach is particularly valuable in the case of biologically active phosphates because of the high intrinsic hydrophilicity and the multitude of biological … WebFeb 8, 2024 · The presence of phosphate mono ester breaking alkaline phosphatase (ALP) enzyme throughout the whole human body, is the main consideration behind the development of phosphate prodrug strategy. WebMay 1, 2001 · Fosphenytoin is a phosphate ester prodrug of phenytoin with an improved solubility and better tolerance after intramuscular or intravenous administration. It is rapidly hydrolyzed in vivo to phenytoin with a half-life of 5–15 min. The prodrug is not pharmacologically active, but it has been shown to cross-react in various immunoassays … how to replace values in python

Prodrugs of Phosphonates, Phosphinates, and Phosphates

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 ... WebEster and phosphate hydrolysis are widely used in prodrug design because of their simplicity, but such approaches are relatively ineffective for targeting drugs to specific sites. The activation of prodrugs by the cytochrome P450 system provides a highly versatile approach to prodrug design that is particularly adaptable for targeting drug ... north bethesda maryland weatherWebNov 13, 2014 · An early focus was pivaloyloxymethyl (POM) modified phosphonates, a prodrug format which was first advanced for use with phosphate monoesters [ 50, 51 ]. However, this approach was readily adapted to phosphonates such as foscarnet esters ( 20) [ 52] and a phosphonate inhibitor of insulin receptor tyrosine kinase [ 53 ]. north bethesda maryland county

"WebMay 20, 2024 · To overcome this problem, various prodrug strategies have been used to mask the carboxylates and/or phosphonate functionalities of 2-PMPA with POM, POC, … " - Phosphate ester prodrug

Phosphate ester prodrug

Prodrugs of phosphonates and phosphates: crossing the membrane barrier

WebJul 31, 2007 · An increasing number of phosphate esters of pharmaceutical interest (mainly antiviral agents and signaling regulators) has encouraged the advancement of the … WebJan 1, 2024 · Phosphate ester group. Phosphate esters are the most commonly used for prodrug synthesis to increase the solubility of poorly water-soluble orally administered drugs as well as for drugs that are administered parenterally (Stella and Nti-Addae, 2007). The phosphate prodrug is acted upon by endogenous phosphatase enzymes like alkaline ...

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WebProdrugs of phosphonates and phosphates: crossing the membrane barrier A substantial portion of metabolism involves transformation of phosphate esters, including pathways … WebFosphenytoin is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. Advantages include more convenient and rapid intravenous administration, availability for intramuscular injection, and low potential for adverse local reactions at injectio …

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 ... WebMar 1, 2003 · Phosphate esters play a dominant role in the physiology of cells and hence are essential to any organism. Most prominent is the participation of phosphate esters as …

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 … WebIn this study, a phosphate group was added to position C-4 of 1, leading to the more water-soluble prodrug 2 and its ammonium salt 3, which possesses increased stability compared to 2. Herein are reported the synthesis, characterization, solubility, and stability of phosphate prodrug 3 in biological medium in comparison to 1 , as well as new ...

WebOnce the prodrug gets into the systemic circulation or target tissues, the ester prodrug moiety may be cleaved through an enzymatic and/or chemical process to release the corresponding free acid of phosphinate, phosphonate, or phosphate to achieve the desirable biological effect.

north bethesda md timeWebGW433908 is the water-soluble, phosphate ester prodrug of the human immunodeficiency virus type 1 protease inhibitor amprenavir (APV). A high-yield synthesis of GW433908 is achieved by phosphorylation of the penultimate precursor of APV with phosphorous oxychloride (POCl(3)) in pyridine. north bethesda ll beanWebMay 23, 2016 · Phosphate Esters In drug design, forming phosphate esters is a common strategy making the drug more soluble in water. In addition to good water solubility, the phosphate ester can also be a site of the substrate for alkaline phosphatases, this property enables the paclitaxel prodrug to have a fast release of the parent drug. how to replace valve seats in headsWebOseltamivir phosphate is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. ... In 2-year carcinogenicity studies in mice and rats given daily oral doses of the prodrug oseltamivir phosphate up to 400 mg/kg and 500 mg/kg, respectively, the prodrug and the active form oseltamivir ... north bethesda parcel gWebPhosphate prodrugs of amines are made to increase solubility, owing to the presence of the highly ionized species in the GI tract. ... Prodrugs are ester derivatives synthesized using the alcoholic functional group at the C-2 or the C-7 position of paclitaxel [70,71]. Such prodrugs have produced cytotoxic activity comparable to paclitaxel ... how to replace vape juiceWebAug 30, 2024 · Phosphonates, often used as isosteric replacements for phosphates, can provide important interactions with an enzyme. Due to their high charge at physiological … north bethesda hourly weatherWebNov 11, 2024 · Main protease (M pro) is a superior target for anti-SARS-COV-2 drugs. PF-07304814 is a phosphate ester prodrug of PF-00835231 that is rapidly metabolized into the active metabolite PF-00835231 by alkaline phosphatase (ALP) and then suppresses SARS-CoV-2 replication by inhibiting M pro. how to replace valve under sink