N-substituted pyrrolidines and tetrahydrofurans as novel AMPAR positive modulators

Bioorg Med Chem Lett. 2010 Dec 1;20(23):7116-9. doi: 10.1016/j.bmcl.2010.09.062. Epub 2010 Sep 17.

Abstract

A series of novel AMPA receptor positive modulators displaying CNS penetration have been discovered with sub-micromolar activity and good selectivity over the cardiac channel receptor, hERG. We describe here the synthesis of these compounds which are biaryl pyrrolidine and tetrahydrofuran sulfonamides and disclose their activities against the human GluA2 flip isoform homotetrameric receptor.

MeSH terms

  • Central Nervous System / metabolism
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / drug effects
  • Furans / chemistry
  • Furans / pharmacology*
  • Humans
  • Protein Isoforms
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / pharmacology*
  • Receptors, AMPA / drug effects*
  • Structure-Activity Relationship
  • Sulfonamides

Substances

  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Furans
  • KCNH2 protein, human
  • Protein Isoforms
  • Pyrrolidines
  • Receptors, AMPA
  • Sulfonamides