苯磺酰胺类IDO1抑制剂的设计、合成和生物活性  

Design,synthesis and biological evaluation of phenylsulfonamide-based IDO1 inhibitors

作　　者：金双龙 王芳[1] 邹毅 王燕 胡月 郭文洁[2] 徐强[2] 赖宜生[1] JIN Shuanglong;WANG Fang;ZOU Yi;WANG Yan;HU Yue;GUO Wenjie;XU Qiang;LAI Yisheng(Center of Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing;210009;2 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University,Nanjing 210093, China)

机构地区：[1]中国药科大学新药研究中心,江苏省代谢性疾病药物重点实验室,南京210009 [2]南京大学生命科学学院,医药生物技术国家重点实验室,南京210093

出　　处：《中国药科大学学报》2018年第1期34-38,共5页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.21472244,No.21472091,No.21772233)

摘　　要：在IDO1抑制剂U-3i的基础上,利用生物电子等排原理,结合分子对接技术,设计并合成了11个苯磺酰胺类目标化合物。采用基于He La细胞的酶学测定方法评价了目标化合物对IDO1活性的影响,结果表明,大多数化合物对IDO1显示不同程度的抑制活性。其中,化合物3b和3e的抑制作用最强,而且能够逆转IDO1介导的免疫抑制,值得进一步研究。Based on the reported ID01inhibitor U-3i,11phenylsulfonamide derivatives were designed and synthesized by adopting bioisosterism and molecular docking technology.The inhibitory activities of the target compounds against ID01were determined by the HeLa cell-based kynurenine assay.The results demonstrated that most compounds showed different degrees of inhibitory effects on IDOl.Among them,compounds3b and3e displayed the most potent activity and could reverse IDO1-mediated immune suppression,which might be worth of further investigation.

关 键 词：ID01抑制剂 苯磺酰胺 合成 生物活性 

分 类 号：R914[医药卫生—药物化学] R965[医药卫生—药学]