Phosphate ester prodrug

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August undefined, 2024

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 … Webprodrug activation processes. Ester prodrugs to enhance oral absorption Oral absorption is a key component of oral bioavailability. Kevin Beaumont (Pfizer Ltd, UK) discussed issues …

Phosphate Prodrugs: An Approach to Improve the ... - ResearchGate

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 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 ... hilb group of nj

Prodrugs of biologically active phosphate esters

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 … 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 … 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 ... smallpox is dead

Synthesis of a highly water-soluble acacetin prodrug for ... - Nature

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 … 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 ... smallpox irelandWebtriphenylethylene 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 smallpox is caused by a/an

"WebAug 30, 2024 · Phosphonates, often used as isosteric replacements for phosphates, can provide important interactions with an enzyme. Due to their high charge at physiological … " - Phosphate ester prodrug

Phosphate ester prodrug

Prodrugs of biologically active phosphate esters

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 … 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, …

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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. … 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.

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. 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 …

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 … WebMay 20, 2024 · ANP prodrugs with suitable pharmacokinetics include amino acid phosphoramidates, pivaloyloxymethyl (POM) and isopropoxycarbonyloxymethyl (POC) esters, alkyl and alkoxyalkyl esters, …

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 ...

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... hilb group needham maWebJul 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 ). smallpox is what type of biological agentWebJan 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 ... hilb oracleWebApr 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 … smallpox is what type of disease hilb oracle bullWebBy 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 ... smallpox isolationWebThe usual strategy for phosphate prodrugs is to modify the acidic oxygen atoms with metabolically labile protecting groups to produce a charge … hilb intranet