A series of AG014699 derivatives containing a novel scaffold of 2,3-dihydro-1H-[1,2]diazepino[4,5,6-cd]indole-1,4(6H)-dione were synthesized and evaluated for their inhibitory activities toward PARP-1 enzyme and two cell lines, MCF-7 cells and the BRCA1-deficient MDA-MB-436 cells. Our results demonstrated that of all AG014699 derivatives synthesized in this work, compounds 6 and 7 showed strong PARP-1 inhibitory activity (IC50=3.5 nM and 2.4 nM, respectively), only four and three times less potent than AG014699. Compound 6 also had significantly cell inhibitory activity against both MCF-7 cells (CC50=25.8 μM) and the BRCA1-deficient MDA-MB-436 cells (CC50=5.4 μM), nearly as good as AG014699, indicating that it can be a promising compound for further evaluation.