Partial structures of ketoconazole as modulators of the large conductance calcium-activated potassium channel (BK(Ca))

Bioorg Med Chem Lett. 2006 Feb 15;16(4):887-90. doi: 10.1016/j.bmcl.2005.11.001. Epub 2005 Dec 15.

Abstract

A series of partial structures of ketoconazole has been synthesized and tested for activity on the large conductance calcium-activated potassium channel (BK) in bovine smooth muscle cells. This has provided openers and blockers of the channel. The results suggest that the phenyl and phenoxy moieties are important for interaction with BK, whereas the imidazole group is unimportant. The properties of the phenoxy moiety seem to determine whether the compounds act to open or block the channel.

MeSH terms

  • Animals
  • Cattle
  • Drug Evaluation, Preclinical
  • Ketoconazole / chemical synthesis
  • Ketoconazole / chemistry
  • Ketoconazole / pharmacology*
  • Large-Conductance Calcium-Activated Potassium Channels / drug effects*
  • Membrane Transport Modulators / chemical synthesis
  • Membrane Transport Modulators / chemistry
  • Membrane Transport Modulators / pharmacology*
  • Molecular Structure
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Structure-Activity Relationship

Substances

  • Large-Conductance Calcium-Activated Potassium Channels
  • Membrane Transport Modulators
  • Ketoconazole