Through conformational restriction of a benzamide by formation of a seven-membered hydrogen-bond with an oxindole carbonyl group, a series of PARP inhibitors was designed for appropriate orientation for binding to the PARP surface. This series of compounds with a 3-oxoisoindoline-4-carboxamide core structure, displayed modest to good activity against PARP-1 in both intrinsic and cellular assays. SAR studies at the lactam nitrogen of the pharmacophore have suggested that a secondary or tertiary amine is important for cellular potency. An X-ray structure of compound 1e bound to the protein confirmed the formation of a seven-membered intramolecular hydrogen bond. Though revealed previously in peptides, this type of seven-membered intramolecular hydrogen bond is rarely observed in small molecules. Largely due to the formation of the intramolecular hydrogen bond, the 3-oxoisoindoline-4-carboxamide core structure appears to be planar in the X-ray structure. An additional hydrogen bond interaction of the piperidine nitrogen to Gly-888 also contributes to the binding affinity of 1e to PARP-1.

通过形成与羟吲哚羰基的七元氢键形成苯甲酰胺的构象限制，设计了一系列PARP抑制剂以使其与PARP表面结合时具有适当的取向。这一系列具有3-氧代异吲哚啉-4-羧酰胺核心结构的化合物在固有和细胞分析中均显示出对PARP-1的适度至良好活性。在药效基团的内酰胺氮上进行的SAR研究表明，仲胺或叔胺对于细胞效能很重要。化合物1e的X射线结构结合到蛋白质上证实了七元分子内氢键的形成。尽管以前在肽中发现过，但这种类型的七元分子内氢键很少在小分子中观察到。在很大程度上，由于分子内氢键的形成，3-氧代异吲哚啉-4-羧酰胺核心结构在X射线结构中似乎是平面的。哌啶氮与Gly-888的其他氢键相互作用也有助于1e与PARP-1的结合亲和力。