Initial SAR studies on apamin-displacing 2-aminothiazole blockers of calcium-activated small conductance potassium channels

Bioorg Med Chem Lett. 2008 Oct 1;18(19):5316-9. doi: 10.1016/j.bmcl.2008.08.023. Epub 2008 Aug 14.

Abstract

An initial SAR study on a series of apamin-displacing 2-aminothiazole K(Ca)2 channel blockers is described. Potent inhibitors such as N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (13) are disclosed, and for select members of the series, the relationship between the observed activity in a thallium flux, a binding and a whole-cell electrophysiology assay is presented.

MeSH terms

  • Apamin / pharmacology*
  • Combinatorial Chemistry Techniques
  • Molecular Structure
  • Potassium Channel Blockers / chemical synthesis*
  • Potassium Channel Blockers / chemistry
  • Potassium Channel Blockers / pharmacology*
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Small-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Thiazoles / chemical synthesis*
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • N-(4-methylpyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine
  • Potassium Channel Blockers
  • Pyridines
  • Small-Conductance Calcium-Activated Potassium Channels
  • Thiazoles
  • Apamin