Design, synthesis, and characterization of BK channel openers based on oximation of abietane diterpene derivatives

Bioorg Med Chem. 2010 Dec 15;18(24):8642-59. doi: 10.1016/j.bmc.2010.09.072. Epub 2010 Nov 8.

Abstract

Oxime ether derivatives at the benzylic position of unsubstituted, dichloro, trichloro, and monobromo derivatives of the aromatic C-ring of dehydroabietic acid and podocarpic acid were synthesized and evaluated as BK channel openers in an assay system of CHO-K1 cells expressing hBKα channels. Detailed SAR analysis showed that the oximation was particularly effective in the cases of dehydroabietic acid derivatives, and some of these oxime derivatives showed more potent BK channel activities than the standard compound, NS1619. The present studies provide a new structural basis for development of efficient BK channel openers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / chemical synthesis*
  • Abietanes / chemistry
  • Abietanes / pharmacology
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Drug Design
  • Humans
  • Large-Conductance Calcium-Activated Potassium Channels / agonists*
  • Large-Conductance Calcium-Activated Potassium Channels / genetics
  • Oximes / chemistry*
  • Structure-Activity Relationship
  • Transduction, Genetic

Substances

  • Abietanes
  • Large-Conductance Calcium-Activated Potassium Channels
  • Oximes