Wang Shaochi, Han Xueqing, Yang Yun, Chen Rui, Guo Zhaoyi, Zhu Qihua, Xu Yungen
State Key Laboratory of Natural Medicines , China Pharmaceutical University , Nanjing , 210009 , China . Email:
Jiangsu Key Laboratory of Drug Design and Optimization , Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing 211198 , China.
RSC Med Chem. 2020 Jun 16;11(7):843-847. doi: 10.1039/d0md00117a. eCollection 2020 Jul 1.
A practical synthetic route, consisting of 5 steps, has been developed and applied successfully for converting limonin/deoxylimonin into the corresponding amino derivatives - and - . Deoxylimonin analogs and bearing an open A ring structure underwent ring closure reaction by employing the Mitsunobu procedure to afford and . All of the 12 newly synthesized compounds were subjected to preliminary screening for evaluating their inflammation and nociception inhibition efficacy. The most promising compounds, and , were selected for further investigation by a carrageenan-induced mouse paw edema model, both of which displayed a dose-response dependent manner and demonstrated superior anti inflammation capacity to that of indomethacin in the first 2 hours.
已开发出一条由5步组成的实用合成路线，并成功应用于将柠檬苦素/去氧柠檬苦素转化为相应的氨基衍生物——和——。具有开环A环结构的去氧柠檬苦素类似物和通过采用光延反应进行闭环反应，得到和。对所有12种新合成的化合物进行了初步筛选，以评估它们的抗炎和镇痛抑制功效。通过角叉菜胶诱导的小鼠足爪肿胀模型，选择了最有前景的化合物和进行进一步研究，这两种化合物均呈现剂量反应依赖性方式，并且在前2小时内显示出优于吲哚美辛的抗炎能力。
