IKCa-channel blockers. Part 2: discovery of cyclohexadienes

Bioorg Med Chem Lett. 2005 Jan 17;15(2):401-4. doi: 10.1016/j.bmcl.2004.10.063.

Abstract

Novel cyclohexadienes have been identified as potent and specific IK(Ca)-channel blockers. In this communication we describe their synthesis as well as their chemical and biological properties. A selected derivative is being enriched in rat brain and reduces the infarct volume, intracranial pressure as well as the water content in a rat subdural hematoma model of traumatic brain injury after iv administration.

MeSH terms

  • Animals
  • Body Water / drug effects*
  • Body Water / metabolism
  • Brain Infarction / drug therapy
  • Brain Injuries / drug therapy
  • Cyclohexanes / chemical synthesis
  • Cyclohexanes / pharmacology*
  • Cyclohexenes
  • Disease Models, Animal
  • Hematoma, Subdural / drug therapy
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Intracranial Pressure / drug effects*
  • Potassium Channel Blockers / chemical synthesis
  • Potassium Channel Blockers / pharmacology*
  • Potassium Channels / metabolism*
  • Rats
  • Structure-Activity Relationship

Substances

  • Cyclohexanes
  • Cyclohexenes
  • Intermediate-Conductance Calcium-Activated Potassium Channels
  • Kcnn4 protein, rat
  • Potassium Channel Blockers
  • Potassium Channels
  • 1,4-cyclohexadiene