| Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception |
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| 作者姓名： | Dengqi Xue Yani Liu Yilin Zheng Heling Niu Liying Dong Xiangshuo Ouyang Siyu Song Denggao Zhang Qianwei Ge Kewei Wang Liming Shao |
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| 作者单位： | 1. School of Pharmacy, Fudan University;2. State Key Laboratory of Medical Neurobiology, Fudan University;3. Department of Pharmacology, School of Pharmacy, Qingdao University Medical College |
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| 基金项目： | Financial supports by National Natural Science Foundation of China (Nos. 82003565 and 81973162)； |
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| 摘 要： | Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide,and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration(IC50) values ranging from2.9 μmol/L to 21.4 μmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy ...
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| 收稿时间： | 4 July 2021 |
Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception |
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| Dengqi Xue,Yani Liu,Yilin Zheng,Heling Niu,Liying Dong,Xiangshuo Ouyang,Siyu Song,Denggao Zhang,Qianwei Ge,Kewei Wang,Liming Shao.Design and synthesis of novel α-aminoamides derivatives as Nav1.7 inhibitors for antinociception[J].Chinese Chemical Letters,2022,33(3):1643-1646. |
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| Institution: | 1. School of Pharmacy, Fudan University, Shanghai 201203, China;2. State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China;3. Department of Pharmacology, School of Pharmacy, Qingdao University Medical College, Qingdao 266071, China |
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| Abstract: | Three novel series of α-aminoamides derivatives were designed and synthesized based on ralfinamide, and their Nav1.7 inhibitory activities were evaluated using manual patch clamp electrophysiology. Active compounds inhibited Nav1.7 with half maximal inhibitory concentration (IC50) values ranging from 2.9 µmol/L to 21.4 µmol/L. Among them, the most potent compound 19h exhibited about 12-fold potency better than ralfinamide. The investigation of their structure-activity relationship gives a strategy to improve the Nav1.7 inhibition of ralfinamide analogues. Compound 19h was efficacious in antinociception in the mouse spared nerve injury (SNI) model of neuropathic pain without causing sedation in the open field test. |
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