Synthesis and biological evaluation of substituted 2-phenyl-2H-indazole-7-carboxamides as potent poly(ADP-ribose) polymerase (PARP) inhibitors.

Abstract A potent series of substituted 2-phenyl-2 H -indazole-7-carboxamides were synthesized and evaluated as inhibitors of poly (ADP-ribose) polymerase (PARP). This extensive SAR exploration culminated with the identification of substituted 5-fluoro-2-phenyl-2 H -indazole-7-carboxamide analog 48 which displayed excellent PARP enzyme inhibition with IC 50  = 4 nM, inhibited proliferation of cancer cell lines deficient in BRCA-1 with CC 50  = 42 nM and showed encouraging pharmacokinetic properties in rats compared to the lead 6 .