Cheng Xin-Yue, Li Yu-Huan, Tang Sheng, Zhang Xin, Wang Yan-Xiang, Wang Sheng-Gang, Jiang Jian-Dong, Li Ying-Hong, Song Dan-Qing
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China.
Eur J Med Chem. 2017 Jan 27;126:133-142. doi: 10.1016/j.ejmech.2016.09.097. Epub 2016 Sep 30.
Twenty-eight new 12N-benzenesulfonyl matrinic butane and halogenated 12N-sulfonyl matrinic butane/ethane derivatives were designed, synthesized and evaluated for their anti-coxsakievirus activities against CVB3 taking compound 1 as the lead. SAR analysis indicated the introduction of a fluoro atom on the 1'-position might be helpful for keeping potency. Among them, compound 8a exhibited potential activities against all CVBs with IC ranging from 0.69 to 5.14 μM, suggesting a broad-spectrum anti-coxsackievirus B feature. In addition, it also displayed an excellent PK and a good safety profile, indicating a highly druggable nature. Thus, we consider compound 8a to be a promising drug candidate in the treatment of not only viral myocarditis caused by CVB3 but also various diseases infected with coxsackieviruses B.
以化合物1为先导，设计、合成了28种新型的12N-苯磺酰基苦参丁烷和卤代12N-磺酰基苦参丁烷/乙烷衍生物，并对其抗柯萨奇病毒B3（CVB3）的活性进行了评估。构效关系分析表明，在1'-位引入氟原子可能有助于保持活性。其中，化合物8a对所有CVB均表现出潜在活性，IC范围为0.69至5.14 μM，显示出广谱抗柯萨奇病毒B的特性。此外，它还具有优异的药代动力学性质和良好的安全性，表明其具有很高的成药潜力。因此，我们认为化合物8a不仅是治疗由CVB3引起的病毒性心肌炎的有前景的候选药物，也是治疗感染柯萨奇病毒B的各种疾病的有前景的候选药物。
