Phosphate ester prodrug

Author: dldy

August undefined, 2024

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 ... WebNov 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 ].

Prodrugs: design and clinical applications Nature Reviews Drug Disco…

WebJul 23, 2024 · The ester family of prodrugs is comprised of molecules where the prodrug has phosphor (mono)ester or phosphodiester bonds connecting the pro-moiety to the rest of the molecule (Fig. 1 ). In this section, we chose to examine PK data for Adefovir, Tenofovir, and Cidofovir (CDV) (Table 1 ). WebBy the design of phosphate ester prodrugs, the poor aqueous solubility of various drugs such as estramustine and prednisolone could be addressed. When given orally these prodrugs rapidly dissolve in gastrointestinal (GI) fluids, yet being efficiently absorbed from the intestinal mucosa. Their high membrane permeability is ascribed to the ... binar protect gmbh

The expanding role of prodrugs in contemporary drug design and …

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 … WebNov 15, 2024 · These eight prodrugs are aripiprazole lauroxil, isavuconazonium sulfate, ixazomib citrate, sacubitril, selexipag, tenofovir alafenamide sulfate, uridine triacetate, and telotristat etiprate with their respective metabolites aripiprazole, isavuconazole, ixazomib, LBQ657, ACT-333679, tenofovir, uridine, and telotristat being pharmacologically … Webtriphenylethylene phosphate prodrug, TAT-59, were also conducted in the rat intestinal perfusion model. Finally, the utility of a phosphate ester prodrug strategy for entacapone to increase that drugs systemic levels was evaluated in rats. MATERIALS AND METHODS Materials TAT-59 and its parent drug, DP-TAT-59, were gifts of binarowa saint michael archangel\\u0027s church

Alkaline Phosphatase: A Reliable Endogenous ... - Wiley Online …

Prodrugs of phosphonates and phosphates: crossing the …

WebNov 13, 2014 · They hold key roles in cell signaling processes, including G-protein coupled receptors (GPCR), second messengers such as cAMP or phosphatidylinositol, and … 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 … binart ccWebMay 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 … bina round

"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. " - Phosphate ester prodrug

Phosphate ester prodrug

Prodrugs of biologically active phosphate esters - ScienceDirect

WebThe result indicated that 1,3‐cyclic propanyl phosphate esters of 18 β‐glycyrrhetic acid have sustained‐release properties to avoid the quick metabolism of 18β‐ glycyRRhetic acid. A new class of potential prodrugs, 1,3‐cyclic propanyl phosphate esters of 18β‐glycyrrhetic acid, was designed and synthesized through the key reaction of 18β‐glycyrrhetic acid with … WebMar 1, 2003 · This approach is particularly valuable in the case of biologically active phosphates because of the high intrinsic hydrophilicity and the multitude of biological …

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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 … 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 ...

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. WebGW433908 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.

WebPhosphate 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 … WebMar 3, 2024 · Cycloalkyl esters of 3',5'-cyclic phosphate nucleotide prodrugs demonstrated the ability to produce high levels of active triphosphate in clone-A cells and primary human hepatocytes.

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.

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 ... bina rothblattWebAug 30, 2024 · Phosphonates, often used as isosteric replacements for phosphates, can provide important interactions with an enzyme. Due to their high charge at physiological … binar profit teamWebSep 1, 2024 · Phenytoin is a low aqueous solubility antiepileptic drug, but its phosphate ester prodrug fosphenytoin is soluble, although less permeable. In a previous study, the intranasal administration of aqueous-based formulations of fosphenytoin led to high but delayed phenytoin bioavailability compared to the intravenous route. cypraea reeveiWebAug 28, 2008 · Preformulation studies were performed on a hemiglutarate ester prodrug of Δ 9-tetrahydrocannabinol (THC-HG), to facilitate the development of stable formulations by hot-melt methods.The various studies performed included solid-state thermal characterization, pKa, logP, aqueous and pH dependent solubility, pH stability and effect … cypraea pantherina syringaWebApr 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 [ … binar pick to lightWebApr 27, 2024 · Fospropofol (Lusedra) is a phosphonooxymethyl prodrug of the sedative or hypnotic drug propofol in which the phosphate promoiety is linked to the sterically … binäruhr the oneWebMay 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. binary 010101 to octal