65223-64-5Relevant 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.
, p. 11034 - 11044 (2020)
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.
PEPTIDE EPOXYKETONE COMPOUNDS
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Paragraph 00280; 00281, (2014/02/16)
The present disclosure relates to novel compounds and pharmaceutical compositions thereof which are useful as inhibitors of proteasomes. The compounds provided herein are capable of inhibiting all three of CT-L, T-L, and PGPH activities of proteasomes, and are useful in treating various conditions or diseases associated with proteasomes.
