Wu Wentao, Li Zhixiang, Yang Guangwen, Teng Mingxing, Qin Jian, Hu Zhijing, Hou Lijuan, Shen Liang, Dong Haiheng, Zhang Yang, Li Jian, Chen Shuhui, Tian Jingwei, Zhang Jianzhao, Ye Liang
WuXi AppTec (Shanghai) Co., Ltd., 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
WuXi AppTec (Shanghai) Co., Ltd., 288 FuTe Zhong Road, Shanghai 200131, People's Republic of China.
Bioorg Med Chem Lett. 2017 May 15;27(10):2210-2215. doi: 10.1016/j.bmcl.2017.03.043. Epub 2017 Mar 18.
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.
hNav1.7小分子抑制剂因其独特的镇痛作用而备受关注。在此，我们报道了一系列新型四氢吡啶类似物作为hNav1.7抑制剂用于镇痛的设计与合成。为了提高hNav1.7活性、体外ADME和体内PK特性，我们进行了详细的构效关系（SAR）研究。这些努力导致了化合物(-)-15h的鉴定，它是一种高效且选择性的hNav1.7抑制剂，具有良好的ADME和PK特性。
