A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects

Bioorg Med Chem Lett. 1999 Oct 18;9(20):2999-3002. doi: 10.1016/s0960-894x(99)00516-8.

Abstract

A series of novel arylpiperidines (4a-d) which have highly potent blocking effects for both neuronal Na+ and T-type Ca2+ channels with extremely low affinity for dopamine D2 receptors were synthesized. Among these compounds, 1-(2-hydroxy-3-phenoxy)propyl-4-(4-phenoxyphenyl)-piperidine hydrochloride (4c; SUN N5030) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (MCAO) model.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, T-Type / drug effects*
  • Epilepsy, Reflex / prevention & control
  • Ischemic Attack, Transient / prevention & control*
  • Mice
  • Mice, Inbred DBA
  • Neuroprotective Agents / pharmacology*
  • Phenyl Ethers / pharmacology*
  • Piperidines / pharmacology*
  • Sodium Channel Blockers*

Substances

  • Anticonvulsants
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Neuroprotective Agents
  • Phenyl Ethers
  • Piperidines
  • SUN N5030
  • Sodium Channel Blockers