204445-50-1Relevant academic research and scientific papers
Prodrug Strategies to Improve the Solubility of the HCV NS5A Inhibitor Pibrentasvir (ABT-530)
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.
supporting information, p. 11034 - 11044 (2020/11/09)
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.
Cryptophycin compounds
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Page/Page column 66-67; 195, (2010/02/05)
The present invention provides cryptophycin compounds of Formula I that are useful in the treatment of neoplasms.
