A novel class of phosphorus-containing Rucaparib analogues were synthesized and evaluated as poly(ADP-ribose) polymerase (PARP) inhibitors. Two distinct series  were designed: one incorporating a spacer and the other without a spacer. Pharmacokinetic evaluation of representative compounds demonstrated favorable oral  bioavailability and improved metabolic stability relative to Rucaparib. Oral administration of compound 9 (20 mg/kg, twice weekly) resulted in significant tumor  growth inhibition (71%) compared to vehicle control and showed superior efficacy over Rucaparib (100 mg/kg, 52% inhibition). Importantly, compound 9 exhibited no  mortality or significant body weight loss, while Rucaparib-treated animals displayed slight weight reduction and mortality in the final week of treatment. Collectively,  these results highlight phosphorus-containing Rucaparib analogues as a promising new class of PARP inhibitors with favorable pharmacological properties and  therapeutic potential for the treatment of BRCA-mutant and homologous recombination–deficient cancers, particularly breast and ovarian malignancies.