T-type calcium channel blockers: spiro-piperidine azetidines and azetidinones-optimization, design and synthesis

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4602-6. doi: 10.1016/j.bmcl.2010.06.012. Epub 2010 Jun 8.

Abstract

A series of spiro-azetidines and azetidinones has been evaluated as novel blockers of the T-type calcium channel (Ca(V)3.2) which is a new therapeutic target for the potential treatment of both inflammatory and neuropathic pain. Confirmation and optimization of the potency, selectivity and DMPK properties of leads will be described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azetidines / chemical synthesis
  • Azetidines / chemistry*
  • Azetidines / therapeutic use
  • Calcium Channel Blockers / chemical synthesis*
  • Calcium Channel Blockers / chemistry
  • Calcium Channel Blockers / therapeutic use
  • Calcium Channels, T-Type / chemistry*
  • Calcium Channels, T-Type / metabolism
  • Drug Design
  • Humans
  • Pain / drug therapy
  • Piperidines / chemistry*
  • Protein Binding
  • Rats
  • Spiro Compounds / chemistry*
  • Structure-Activity Relationship

Substances

  • 2-azetidinone
  • Azetidines
  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Piperidines
  • Spiro Compounds
  • piperidine