Poly(ADP-ribose)polymerase (PARP) is a significant therapeutic target for the treatment of numerous human diseases. Olaparib has been approved as a PARP inhibitor. In this paper, a series of new compounds were designed and synthesized with Olaparib as the lead compound. In order to evaluate the inhibitory activities against PARP1 of the synthesized compounds, in vitro PARP1 inhibition assay and intracellular PARylation assay were conducted. The results showed that the inhibitory activities of the derivatives were related to the type of substituent and the length of alkyl chain connecting the aromatic ring. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT)-based assay also proved that these compounds demonstrating strong inhibition to PARP1 also have high anti-proliferative activities against BRCA2-deficient cell line (Capan-1). Analysis of the entire results suggest that compound 23 with desirable inhibitory efficiency may hold promise for further in vivo exploration of PARP inhibition.

聚（ADP-核糖）聚合酶（PARP）是治疗多种人类疾病的重要治疗靶点。奥拉帕尼已被批准作为 PARP 抑制剂。本文以奥拉帕尼为先导化合物，设计合成了一系列新化合物。为了评估合成化合物对PARP1的抑制活性，进行了体外PARP1抑制试验和细胞内PARylation试验。结果表明，衍生物的抑制活性与取代基的类型和连接芳环的烷基链长度有关。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2 H基于溴化四唑 (MTT) 的测定还证明，这些对 PARP1 表现出强烈抑制作用的化合物也对 BRCA2 缺陷细胞系 (Capan-1) 具有高抗增殖活性。对整个结果的分析表明，具有理想抑制效率的化合物23有望进一步在体内探索 PARP 抑制。