The discovery of tetrahydropyridine analogs as hNav1.7 selective inhibitors for analgesia

[Display omitted] 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.