Selection of QPX7831, an Orally Bioavailable Prodrug of Boronic Acid β-Lactamase Inhibitor QPX7728
K. Raja Reddy, Jonathan Parkinson, Mojgan Sabet, Ziad Tarazi, Serge H. Boyer, Olga Lomovskaya, David C. Griffith, Scott J. Hecker, Michael N. Dudley
Abstract
In recognition of the need for effective oral therapies to treat Gram-negative bacterial infections, efforts were directed toward identifying an oral prodrug of β-lactamase inhibitor clinical candidate QPX7728. Seventeen prodrugs were synthesized; key properties investigated were rates of cleavage to the active form in vitro, pharmacokinetics across species, and crystallinity. Compound 5-Na (QPX7831 Sodium) emerged with optimal properties across all key attributes.
Topics & Concepts
ProdrugChemistryBioavailabilityPharmacokineticsPharmacologyOral administrationOrally activeBoronic acidAntibioticsIn vitroCombinatorial chemistryBiochemistryMedicineAntibiotic Resistance in BacteriaAntibiotics Pharmacokinetics and EfficacyPneumocystis jirovecii pneumonia detection and treatment