A series of exiguamine A analogues were designed and synthesized via 15 steps. Their inhibitory activities against IDO1 were tested and the structure-activity relationships were studied. Most compounds exhibited potent IDO1 inhibitory activities with IC₅₀ values at the level of 10⁻⁷–10⁻⁸ M. Compound 21f was the most potent IDO1 inhibitor with an IC₅₀ value of 65.3 nM, which was comparable with the positive control drug epacadostat (IC₅₀ = 46 nM). Moreover, compound 21f showed higher selectivity for IDO1 over tryptophan 2,3-dioxygenase (TDO) and no cytotoxicity at its effective concentration, rending it justifiable for further optimization and evaluation.

通过 15 个步骤设计和合成了一系列 exiguamine A 类似物。测试了它们对 IDO1 的抑制活性，并研究了构效关系。大多数化合物表现出有效的 IDO1 抑制活性，IC ₅₀值为 10 ^-7 –10 ^-8  M。化合物21f是最有效的 IDO1 抑制剂，IC ₅₀值为 65.3 nM，与阳性对照药物 epacadostat 相当(IC ₅₀  = 46 nM)。此外，化合物21f对 IDO1 显示出比色氨酸 2,3-双加氧酶 (TDO) 更高的选择性，并且在其有效浓度下没有细胞毒性，这使其有理由进一步优化和评估。