Novel cyclopentane dicarboxamide sodium channel blockers as a potential treatment for chronic pain

Bioorg Med Chem Lett. 2005 Apr 1;15(7):1901-7. doi: 10.1016/j.bmcl.2005.02.002.

Abstract

A series of new voltage-gated sodium channel blockers were prepared based on the screening lead succinic diamide BPBTS. Replacement of the succinimide linker with the more rigid cyclic 1,2-trans-diamide linker was well tolerated. N-Methylation on the biphenylsulfonamide side of the amide moiety significantly reduced the clearance rate in rat pharmacokinetic studies.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Amides / therapeutic use
  • Analgesics / chemical synthesis
  • Analgesics / pharmacology
  • Animals
  • Biphenyl Compounds / chemistry
  • Cyclopentanes / chemical synthesis
  • Cyclopentanes / pharmacology*
  • Cyclopentanes / therapeutic use
  • Ion Channel Gating / drug effects
  • Methylation
  • Mexiletine / pharmacology
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Rats
  • Sodium Channel Blockers / chemical synthesis*
  • Sodium Channel Blockers / pharmacology
  • Sodium Channel Blockers / therapeutic use
  • Structure-Activity Relationship
  • Succinates / chemistry
  • Sulfonamides / chemistry

Substances

  • Amides
  • Analgesics
  • Biphenyl Compounds
  • Cyclopentanes
  • Sodium Channel Blockers
  • Succinates
  • Sulfonamides
  • cyclopentane dicarboxamide
  • Mexiletine