Phosphate ester prodrug

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August undefined, 2024

WebNov 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. WebJun 28, 2008 · A series of amino acid monoester prodrugs of floxuridine was synthesized and evaluated for the improvement of oral bioavailability and the feasibility of target drug delivery via oligopeptide transporters. All floxuridine 5′-amino acid monoester prodrugs exhibited PEPT1 affinity, with inhibition coefficients of Gly-Sar uptake (IC50) ranging from …

Review of preclinical data of PF-07304814 and its active ... - PubMed

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, … 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 … high five to go pforzheim

Prodrugs of biologically active phosphate esters

WebMay 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. 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. WebOseltamivir 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 ... how humans are wasting water

Phosphoryl prodrugs: characteristics to improve drug development …

Prodrugs of biologically active phosphate esters

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 ... 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 ). high five training nova scotiaWebPhosphate 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 ... highfivetraining prontario.org

"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. " - Phosphate ester prodrug

Phosphate ester prodrug

WebMay 10, 2016 · It is well recognized that phosphate ester-based prodrugs could be converted into parent compounds by alkaline phosphatase 15, 19 which is present in all tissues in the body 20. 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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WebMar 3, 2024 · Cyclic phosphate ester derivative 18c exhibits much higher anti-proliferative activity than positive control NUC-1031 with IC 50 s of 3.6–19.2 nM on multiple cancer … 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 …

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 ]. WebJul 31, 2007 · An increasing number of phosphate esters of pharmaceutical interest (mainly antiviral agents and signaling regulators) has encouraged the advancement of the …

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. Weborganophosphate. [ or″gah-no-fos´fāt] an organic ester of a phosphate such as phosphoric acid with an organic compound such as glucose or sorbitol; see also organophosphorus. …

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 [ …

how humans can help animalsWebtriphenylethylene 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 high five transportWeb3. 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). high five transportationWebAug 30, 2024 · Phosphonates, often used as isosteric replacements for phosphates, can provide important interactions with an enzyme. Due to their high charge at physiological … how humans changeWebAug 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 … high five training ontarioWebApr 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 … how humans came to earthWebMay 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 humans can help climate change