Authors Randolph, JT; Voight, EA; Greszler, SN; Uno, BE; Newton, JN; Gleason, KM; Stolarik, D; Van Handel, C; Bow, DAJ; DeGoey, DA in AMER CHEMICAL SOC published article about PROTEASE INHIBITORS; PHARMACOKINETICS; GLECAPREVIR; NUCLEOSIDE; DESIGN; SAFETY; SINGLE in [Randolph, John T.; Voight, Eric A.; Greszler, Stephen N.; Uno, Brice E.; Newton, James N.; Gleason, Kenneth M.; Stolarik, DeAnne; Van Handel, Cecilia; Bow, Daniel A. J.; DeGoey, David A.] Abbvie Inc, Global Pharmaceut Res & Dev, N Chicago, IL 60064 USA in 2020, Cited 26. Recommanded Product: 87-41-2. The Name is Isobenzofuran-1(3H)-one. Through research, I have a further understanding and discovery of 87-41-2
A research program to discover solubilizing prodrugs of the HCV NS5A inhibitor pibrentasvir (PIB) identified phosphomethyl analog 2 and trimethyl-lock (TML) prodrug 9. The prodrug moiety is attached to a benzimidazole nitrogen atom via an oxymethyl linkage to allow for rapid and complete release of the drug for absorption following phosphate removal by intestinal alkaline phosphatase. These prodrugs have good hydrolytic stability properties and improved solubility compared to PIB, both in aqueous buffer (pH 7) and FESSIF (pH 5). TML prodrug 9 provided superior in vivo performance, delivering high plasma concentrations of PIB in PK studies conducted in mice, dogs, and monkeys. The improved dissolution properties of these phosphate prodrugs provide them the potential to simplify drug dosage forms for PIB-containing HCV therapy.
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