Synthesis and biological evaluation of 6-aryl-6H-pyrrolo[3,4-d]pyridazine derivatives as high-affinity ligands of the alpha(2)delta subunit of voltage-gated calcium channels

Bioorg Med Chem Lett. 2004 May 3;14(9):2031-4. doi: 10.1016/j.bmcl.2004.02.070.

Abstract

A novel class of 2H-pyrrolo[3,4-c]pyridazine ligands of the alpha (2) delta subunit of voltage-gated calcium channels is described. Compound 4a with high affinity toward alpha (2) delta was identified through structure-activity relationship studies of the lead compound. Tritiated ligand [(3)H]-4b was synthesized to demonstrate that this ligand binds to the same site as Gabapentin toward alpha (2) delta subunit of voltage-gated calcium channels.

MeSH terms

  • Calcium Channels / drug effects*
  • Drug Evaluation, Preclinical
  • Ion Channel Gating*
  • Ligands
  • Pyridazines / chemical synthesis*
  • Pyridazines / chemistry
  • Pyridazines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Calcium Channels
  • Ligands
  • Pyridazines
  • pyridazine