萘环类PD-1/PD-L1抑制剂的设计、合成及生物活性评价
Design, Synthesis and Biological Evaluation of Naphthalene Ring PD-1/PD-L1 Inhibitors
DOI: 10.12677/HJMCe.2021.92012, PDF,    国家自然科学基金支持
作者: 赵 磊, 欧阳宜强, 赖宜生*：中国药科大学，新药研究中心，天然药物活性组分与药效国家重点实验室，江苏省代谢性疾病药物重点实验室，江苏 南京；余龙波, 郭文洁, 徐 强, 高 健*：南京大学，生命科学学院，医药生物技术国家重点实验室，江苏 南京
关键词: 肿瘤免疫治疗；免疫检查点；PD-1/PD-L1抑制剂；生物活性；Tumor Immunotherapy； Immune Checkpoint； PD-1/PD-L1 Inhibitor； Biological Activity
摘要: 以BMS-1018为先导化合物，通过替换联苯片段为萘环以及生物电子等排原理，结合分子对接技术，设计并合成了两个系列共18个新型萘环类PD-1/PD-L1小分子抑制剂，结构经1H-NMR和ESI-MS谱确证。采用均相时间分辨荧光法评价目标化合物对PD-1/PD-L1结合的抑制活性。结果表明，所有目标化合物对PD-1/PD-L1均显示不同程度的抑制活性。其中6个化合物A-8、A-9和B-5、B-6、B-8、B-9的活性较为突出，值得进一步研究。
Abstract: Using BMS-1018 as the lead compound, two series of novel naphthalene-based PD-1/PD-L1 small molecule inhibitors were designed and synthesized by replacing the biphenyl moiety with a naph-thalene ring and applying the principle of bioisosterism combined with molecular docking technol-ogy. The structures of the target compounds were confirmed by 1H-NMR and ESI-MS. The inhibitory activity of the compounds against the PD-1/PD-L1 interaction was evaluated by homogeneous time-resolved fluorescence. The results showed that all the target compounds displayed different degrees of inhibitory activity. Among them, six compounds A-8, A-9 and B-5, B-6, B-8, B-9 have out-standing activities, which are worthy of further study.
文章引用：赵磊, 余龙波, 欧阳宜强, 郭文洁, 徐强, 高健, 赖宜生. 萘环类PD-1/PD-L1抑制剂的设计、合成及生物活性评价[J]. 药物化学, 2021, 9(2): 94-103. https://doi.org/10.12677/HJMCe.2021.92012

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