In this work, two series of cyclic amine-containing benzimidazole carboxamide derivatives were designed and synthesized as potent anticancer agents. PARP1/2 inhibitory activity assays indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was investigated against four human cancer cell lines (MDA-MB-436, MDA-MB-231, MCF-7 and CAPAN-1), and several compounds exhibited strong cytotoxicity to tumor cells. Among them, 2-(1-(4,4-difluorocyclohexyl)piperidin-4-yl)-1H-benzo[d]imidazole-4-carboxamide (17d) was found to be effective PARP1/2 inhibitors (IC₅₀ = 4.30 and 1.58 nM, respectively). In addition, 17d possessed obvious selective antineoplastic activity and noteworthy microsomal metabolic stability. What’s more, further studies revealed that 17d was endowed with an excellent ADME profile. These combined results indicated that 17d could be a promising candidate for the treatment of cancer.

在这项工作中，设计并合成了两个系列的含环胺苯并咪唑甲酰胺衍生物作为有效的抗癌剂。 PARP1/2 抑制活性测定表明大多数化合物显示出显着的活性。研究了这些化合物针对四种人类癌细胞系（MDA-MB-436、MDA-MB-231、MCF-7 和 CAPAN-1）的体外抗增殖活性，其中几种化合物对肿瘤细胞表现出强烈的细胞毒性。其中，2-(1-(4,4-二氟环己基)哌啶-4-基)-1H-苯并[ d ]咪唑-4-甲酰胺( 17d )被发现是有效的PARP1/2抑制剂(IC ₅₀ = 4.30)和 1.58 nM，分别）。此外， 17d具有明显的选择性抗肿瘤活性和值得注意的微粒体代谢稳定性。更重要的是，进一步的研究表明， 17d具有出色的 ADME 特性。这些综合结果表明17d可能是治疗癌症的有希望的候选者。