185331-04-8Relevant articles and documents
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.
PRODRUG MODULATORS OF THE INTEGRATED STRESS PATHWAY
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Paragraph 00276; 00280, (2020/05/19)
Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.
ADENOSINE RECEPTOR ANTAGONISTS AND USES THEREOF
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Paragraph 00305; 00306, (2019/10/01)
Disclosed herein are compounds, compositions, formulations, and methods for modulating the A2B adenosine receptor.
Prodrugs of compounds that inhibit TRPV1 receptor
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Page/Page column 20, (2010/11/27)
Compounds of formula (I) wherein A, R1, R2, and R3 are defined in the specification, and which are useful as therapeutic compounds particularly for treating disorders or conditions associated with inflammation, pain, bladd