Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. However, there is a growing demand for novel small-molecule IFN inducer due to tolerance, toxicity, or short duration of action following direct administration of IFNs. In this study, we assessed arylpiperazine (ARP) as a new core skeleton of IFN inducer. To investigate structure–activity relationship, we designed and synthesized a series of ARP analogues and evaluated the ability to stimulate IFN response in THP-1 human monocyte cells. Compound 5i was identified as a potent type I IFN inducer as it significantly increased cytokine secretion and increased expression of various IFN-stimulating genes which are representative biomarkers of type I IFN pathway. Our results suggested a beneficial therapeutic potential of 5i as an anti-viral agent.

I型干扰素（IFN）信号传导在抵抗病毒感染的免疫防御系统和先天免疫应答中起着重要作用，因此IFN被广泛用作抗病毒剂和免疫紊乱或癌症的治疗方法。然而，由于耐受性，毒性或直接施用IFN后的短作用时间，对新型小分子IFN诱导剂的需求不断增长。在这项研究中，我们评估了芳基哌嗪（ARP）作为IFN诱导剂的新核心骨架。为了研究结构与活性之间的关系，我们设计并合成了一系列ARP类似物，并评估了在THP-1人单核细胞中刺激IFN反应的能力。化合物5i被鉴定为有效的I型IFN诱导剂，因为它显着增加了细胞因子的分泌并增加了各种IFN刺激基因的表达，这些基因是I型IFN途径的代表性生物标志物。我们的结果表明5i作为抗病毒药物具有有益的治疗潜力。