Discovery and evaluation of Ca v 3.2-selective T-type calcium channel blockers

Bioorg Med Chem Lett. 2017 Dec 1;27(23):5326-5331. doi: 10.1016/j.bmcl.2017.09.062. Epub 2017 Sep 30.

Abstract

We identified and characterized a series of pyrrole amides as potent, selective Cav3.2-blockers. This series culminated with the identification of pyrrole amides 13b and 26d, with excellent potencies and/or selectivities toward the Cav3.1- and Cav3.3-channels. These compounds display poor physicochemical and DMPK properties, making their use difficult for in vivo applications. Nevertheless, they are well-suited for in vitro studies.

Keywords: Absence-type epilepsy; Pyrroles; Selective Cav3.2-blockers; T-type calcium channel.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry
  • Amides / pharmacology*
  • Animals
  • Calcium Channel Blockers / chemical synthesis
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, T-Type / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Humans
  • Molecular Structure
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Pyrroles / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • Amides
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Pyrroles