%0 Journal Article
%T 萘环类PD-1/PD-L1抑制剂的设计、合成及生物活性评价<br>Design, Synthesis and Biological Evaluation of Naphthalene Ring PD-1/PD-L1 Inhibitors
%A 赵磊
%A 余龙波
%A 欧阳宜强
%A 郭文洁
%A 徐强
%A 高健
%A 赖宜生
%J Hans Journal of Medicinal Chemistry
%P 94-103
%@ 2331-8295
%D 2021
%I Hans Publishing
%R 10.12677/HJMCe.2021.92012
%X 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。<br />
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.
%K 肿瘤免疫治疗，免疫检查点，PD-1/PD-L1抑制剂，生物活性<br>Tumor Immunotherapy
%K Immune Checkpoint
%K PD-1/PD-L1 Inhibitor
%K Biological Activity
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=42812