Structure-activity relationship of N-methyl-N-aralkyl-peptidylamines as novel N-type calcium channel blockers

Bioorg Med Chem Lett. 1999 Aug 2;9(15):2151-6. doi: 10.1016/s0960-894x(99)00359-5.

Abstract

Selective N-type voltage sensitive calcium channel (VSCC) blockers have shown efficacy in several animal models of stroke and pain. In the process of searching for small molecule N-type calcium channel blockers, we have identified a series of N-methyl-N-aralkyl-peptidylamines with potent functional activity at N-type VSCCs. The most active compound discovered in this series is PD 173212 (11, IC50 = 36 nM in the IMR-32 assays). SAR and pharmacological evaluation of this series are described.

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Disease Models, Animal
  • Humans
  • Mice
  • Seizures / drug therapy
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • Dipeptides
  • PD 173212