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目的 设计合成2类1H-吲唑类新化合物,并测试其吲哚胺2,3-双加氧酶1 (IDO1)抑制活性.方法 以肿瘤免疫关键调控蛋白IDO1作为靶标,依据IDO1活性位点的关键药效团特征,利用合理药物设计方法,以前期研究获得的高活性化合物作为先导化合物,设计合成了2类1H-吲唑类衍生物,并测试其体外IDO1酶抑制活性.采用分子对接软件DOCK6进行分子对接模拟并分析化合物的构效关系.结果与结论 合成了5个1H-吲唑类衍生物,均表现出不同程度的IDO1抑制活性,其中化合物2a和3b的抑制活性较好,在100 μmol· L-1时的抑制率均为69％.构效关系和分子对接研究显示,4位连接基团的结构对化合物活性影响很大,1H-吲唑类化合物还有很大结构优化空间,极具开发潜力,可为靶向IDO1的肿瘤免疫治疗提供候选化合物.“,”Cancer immunotherapies promise to be an innovation in the treatment of cancer following surgicaltreatment,chemotherapy,radiotherapy,and targeted therapy,because of distinguished effectiveness and novelty.Indoleamine 2,3-dioxygenase 1 (IDO1) is an attractive target of cancer immunotherapy,and it has demonstrated remarkable value in the cancer treatment.Based on the key pharmacophore features of IDO active sites,two series of new 1H-indazoles were designed and synthesized via rational drug design methods.These 1H-indazole derivatives were determined the enzyme inhibitory activities,and compounds 2a and 3b exhibited the highest activities with inhibition ratio 69％ at 100 μmol· L-1.The structure-activity relationships (SARs) analysis and docking model of the 1H-indazole derivatives as novel IDO1 inhibitors indicated that the linker groups at the 4-position largely affect inhibitory activity.In view of structural optimized potential of 1H-indazoles,the study suggested that 1H-indazoles have the potential to be the novel IDO pharmacological inhibitors and thus to provide the candidate compounds of IDO-targeted cancer immunotherapy agents.