The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel openers targeted for post-stroke neuroprotection

Bioorg Med Chem Lett. 2002 Jul 8;12(13):1779-83. doi: 10.1016/s0960-894x(02)00240-8.

Abstract

A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in Xenopus laevis oocytes using electrophysiological methods. A brain penetrable activator of maxi-K channels was identified and shown to be significantly active in the MCAO model of stroke.

MeSH terms

  • Animals
  • Brain / drug effects
  • Clone Cells
  • Disease Models, Animal
  • Electrophysiology
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Membrane Potentials
  • Neuroprotective Agents / blood
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology
  • Oocytes / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels, Calcium-Activated / drug effects
  • Potassium Channels, Calcium-Activated / metabolism*
  • Quinolones / blood
  • Quinolones / chemical synthesis
  • Quinolones / chemistry*
  • Quinolones / pharmacology
  • Rats
  • Stroke / complications
  • Stroke / drug therapy
  • Structure-Activity Relationship
  • Xenopus laevis

Substances

  • Large-Conductance Calcium-Activated Potassium Channels
  • Neuroprotective Agents
  • Potassium Channels, Calcium-Activated
  • Quinolones