Synthesis and evaluation of boron-containing heterocycles as drug candidates: Benzoxazaborinins as PARP inhibitors

• Organoboron compounds have attracted increased attention in the field of medicinal chemistry due to their ability to elicit direct drug-enzyme interactions. Our intent was to explore boron containing heterocycles as poly(ADP-ribose) polymerase (PARP) inhibitors. • In this study, we have created a series of boron-containing heterocyclic compounds that includes 21 benzoxazaborinin derivatives, in yields ranging from 20% to 99%. • We were able to synthesize benzoxazaborinin-based PARP inhibitors, with molecule 15A displaying the best potency with the lowest IC50 value of 31 mM. • Overall, we have shown that benzoxazaborinins can serve as effective PARP inhibitors in the mM range. The inhibition of poly(ADP-Ribose) polymerase (PARP) has been utilized therapeutically for the treatment of BRCA-deficient breast, ovarian and prostate cancer. Organoboron compounds have attracted increased attention in the field of medicinal chemistry due to their ability to elicit direct drug-enzyme interactions. In this study, we have created a series of boron-containing heterocyclic compounds that includes 21 benzoxazaborinin derivatives, in yields ranging from 20% to 99%. These benzoxazaborinin compounds are characterized by utilizing NMR spectroscopy and HRMS, and tested for PARP inhibition with a PARP-1 screening assay, which is both cost-effective and does not require special laboratory equipment. Overall, we were able to synthesize benzoxazaborinin-based PARP inhibitors, which are utilized as breast and ovarian cancer drugs. Molecule 15A displays the best potency with the lowest IC50 value of 31 μM.