Discovery and evaluation of selective N-type calcium channel blockers: 6-unsubstituted-1,4-dihydropyridine-5-carboxylic acid derivatives

Bioorg Med Chem Lett. 2012 Jun 1;22(11):3639-42. doi: 10.1016/j.bmcl.2012.04.051. Epub 2012 Apr 17.

Abstract

A structure-activity relationship study of 6-unsubstituted-1,4-dihydropyridine and 2,6-unsubstituted-1,4-dihydropyridine derivatives was conducted in an attempt to discover N-type calcium channel blockers that were highly selective over L-type calcium channel blockers. Among the tested compounds, (+)-4-(3,5-dichloro-4-methoxy-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-cinnamyl ester was found to be an effective and selective N-type calcium channel blocker with oral analgesic potential.

MeSH terms

  • Administration, Oral
  • Analgesics / chemical synthesis
  • Analgesics / chemistry*
  • Analgesics / pharmacology
  • Animals
  • Calcium Channel Blockers / chemical synthesis
  • Calcium Channel Blockers / chemistry*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, N-Type / chemistry*
  • Calcium Channels, N-Type / metabolism
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry*
  • Carboxylic Acids / pharmacology
  • Dihydropyridines / chemistry*
  • Drug Evaluation, Preclinical
  • Formaldehyde / toxicity
  • Pain Measurement / drug effects
  • Rats
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Carboxylic Acids
  • Dihydropyridines
  • Formaldehyde
  • 1,4-dihydropyridine