Optimized synthesis and pharmacological evaluation of HCN channel inhibitor EC18

Arch Pharm (Weinheim). 2023 Jun;356(6):e2200665. doi: 10.1002/ardp.202200665. Epub 2023 Mar 22.

Abstract

HCN4 channels are considered to be a promising target for cardiac pathologies, epilepsy, and multiple sclerosis. However, there are no subtype-selective HCN channel blockers available, and only a few compounds are reported to display subtype preferences, one of which is EC18 (cis-1). Herein, we report the optimized synthetic route for the preparation of EC18 and its evaluation in three different pharmacological models, allowing us to assess its activity on cardiac function, thalamocortical neurons, and immune cells.

Keywords: EC18; HCN channel; HCN4; iPSC; ion channels.

MeSH terms

  • Cyclic Nucleotide-Gated Cation Channels* / metabolism
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Neurons / metabolism
  • Potassium Channels*
  • Structure-Activity Relationship

Substances

  • Potassium Channels
  • Cyclic Nucleotide-Gated Cation Channels
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels