The discovery of tetrahydropyridine analogs as hNav1.7 selective inhibitors for analgesia |
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| Authors: | Wentao Wu Zhixiang Li Guangwen Yang Mingxing Teng Jian Qin Zhijing Hu Lijuan Hou Liang Shen Haiheng Dong Yang Zhang Jian Li Shuhui Chen Jingwei Tian Jianzhao Zhang Liang Ye |
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| Institution: | 1. WuXi AppTec (Shanghai) Co., Ltd., 288 FuTe Zhong Road, Shanghai 200131, People’s Republic of China;2. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, People''s Republic of China |
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| Abstract: | hNav1.7 small molecular inhibitors have attracted lots of attention by its unique analgesic effect. Herein, we report the design and synthesis of a novel series of tetrahydropyridine analogs as hNav1.7 inhibitors for analgesia. Detail structural–activity relationship (SAR) studies were undertaken towards improving hNav1.7 activity, in vitro ADME, and in vivo PK profiles. These efforts resulted in the identification of compound (?)-15h, a highly potent and selective hNav1.7 inhibitor with good ADME and PK profiles. |
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| Keywords: | Voltage-gated sodium channel Tetrahydropyridine Pain Analgesia |
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