Inhibition of N-type calcium channels by fluorophenoxyanilide derivatives

Mar Drugs. 2015 Apr 13;13(4):2030-45. doi: 10.3390/md13042030.

Abstract

A set of fluorophenoxyanilides, designed to be simplified analogues of previously reported ω-conotoxin GVIA mimetics, were prepared and tested for N-type calcium channel inhibition in a SH-SY5Y neuroblastoma FLIPR assay. N-type or Cav2.2 channel is a validated target for the treatment of refractory chronic pain. Despite being significantly less complex than the originally designed mimetics, up to a seven-fold improvement in activity was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / chemical synthesis
  • Analgesics, Non-Narcotic / chemistry
  • Analgesics, Non-Narcotic / metabolism
  • Analgesics, Non-Narcotic / pharmacology*
  • Anilides / chemical synthesis
  • Anilides / chemistry
  • Anilides / metabolism
  • Anilides / pharmacology*
  • Binding, Competitive
  • Calcium Channel Blockers / chemical synthesis
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels, N-Type / chemistry
  • Calcium Channels, N-Type / metabolism*
  • Calcium Signaling / drug effects
  • Cell Line, Tumor
  • Drug Design*
  • Fluorobenzenes / chemical synthesis
  • Fluorobenzenes / chemistry
  • Fluorobenzenes / metabolism
  • Fluorobenzenes / pharmacology
  • High-Throughput Screening Assays
  • Humans
  • Molecular Structure
  • Molecular Targeted Therapy
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Neuralgia / drug therapy
  • Neuralgia / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotoxins / chemistry
  • Pain, Intractable / drug therapy
  • Pain, Intractable / metabolism
  • Structure-Activity Relationship
  • omega-Conotoxin GVIA / chemistry
  • omega-Conotoxin GVIA / metabolism
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Analgesics, Non-Narcotic
  • Anilides
  • CACNA1B protein, human
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Fluorobenzenes
  • Nerve Tissue Proteins
  • Neurotoxins
  • omega-Conotoxin GVIA