Selection of QPX7831, an Orally Bioavailable Prodrug of Boronic Acid β‑Lactamase Inhibitor QPX7728

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.