Synthesis and Evaluation of Novel α-Aminoamides Containing an Indole Moiety for the Treatment of Neuropathic Pain

• Main Authors: Haotian Li, Shiyong Fan, Jingchao Cheng, Ping Zhang, Bohua Zhong, Weiguo Shi
• Format: Article
• Language: English
• Published: MDPI AG 2016-06-01
• Series: Molecules
• Subjects: neuropathic pain; α-aminoamide derivatives; voltage-gated sodium channel blockers
• Online Access: http://www.mdpi.com/1420-3049/21/7/793

The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted.