Discovery and evaluation of Cav3.1-selective T-type calcium channel blockers

Bioorg Med Chem Lett. 2017 Dec 1;27(23):5322-5325. doi: 10.1016/j.bmcl.2017.09.063. Epub 2017 Oct 3.

Abstract

We identified and characterized a series of pyrazole amides as potent, selective Cav3.1-blockers. This series culminated with the identification of pyrazole amides 5a and 12d, with excellent potencies and/or selectivities toward the Cav3.2- and Cav3.3-channels. This compound displays poor DMPK properties, making its use difficult for in vivo applications. Nevertheless, this compound as well as analogous ones are well-suited for in vitro studies.

Keywords: Pyrazoles; Selective Ca(v)3.1-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