Design and synthesis of novel phthalazinone derivatives as potent poly(ADP-ribose)polymerase 1 inhibitors.

The development of effective PARP-1 inhibitors has received great enthusiasm in medicinal chemistry communities. A new series of novel phthalazinone derivatives were designed and synthesized. Among these, and displayed more potent PARP-1 inhibitory activities than olaparib. gave an IC value of 7.8 nM against PARP-1, and a PF value of 3.4 in the sensitizing effect assay. The pharmacokinetic properties evaluation showed displayed insufficient oral exposure, and it was also not stable in rat blood. The results indicated that our design phthalazinone derivatives were potent PARP-1 inhibitors, and compound was a valuable lead compound with significant  efficacy, deserving further optimization to develop anticancer drug candidate.