Inhibition of N-type calcium channels by fluorophenoxyanilide derivatives.

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.

• Authors: Ellen C Gleeson, Janease E Graham, Sandro Spiller, Irina Vetter, Richard J Lewis, Peter J Duggan, Kellie L Tuck
• Journal: Marine drugs (Mar Drugs) Vol. 13 Issue 4 Pg. 2030-45 (Apr 13 2015) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 25871286 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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