Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain

Molecules. 2021 Mar 19;26(6):1716. doi: 10.3390/molecules26061716.

Abstract

Novel α-aminoamide derivatives containing different benzoheterocyclics moiety were synthesized and evaluated as voltage-gated sodium ion channels blocks the treatment of pain. Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Nav1.7 and anti-Nav1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Nav targets, could serve as new leads for the development of analgesic medicines.

Keywords: Nav1.7; Nav1.8; dual channel inhibitors; sodium channel blocker; α-aminoamides.

MeSH terms

  • Amides* / chemical synthesis
  • Amides* / chemistry
  • Amides* / pharmacology
  • Analgesics* / chemical synthesis
  • Analgesics* / chemistry
  • Analgesics* / pharmacology
  • Animals
  • Drug Evaluation
  • Male
  • Mice
  • NAV1.7 Voltage-Gated Sodium Channel / metabolism
  • NAV1.8 Voltage-Gated Sodium Channel / metabolism
  • Pain / chemically induced
  • Pain / drug therapy*
  • Pain / metabolism
  • Sodium Channel Blockers* / chemical synthesis
  • Sodium Channel Blockers* / chemistry
  • Sodium Channel Blockers* / pharmacology

Substances

  • Amides
  • Analgesics
  • NAV1.7 Voltage-Gated Sodium Channel
  • NAV1.8 Voltage-Gated Sodium Channel
  • Scn10a protein, mouse
  • Scn9a protein, mouse
  • Sodium Channel Blockers