Synthesis and structure-activity relationship studies of conformationally flexible tetrahydroisoquinolinyl triazole carboxamide and triazole substituted benzamide analogues as σ2 receptor ligands

J Med Chem. 2014 May 22;57(10):4239-51. doi: 10.1021/jm5001453. Epub 2014 May 12.

Abstract

Two novel classes of compounds targeting the sigma-2 (σ2) receptor were synthesized, and their bioactivities to binding σ1 and σ2 receptors were measured. Four novel triazole carboxamide analogues, 24d, 24e, 24f, and 39c, demonstrated high affinity and selectivity for the σ2 receptor. These data suggest (11)C-labeled versions of these compounds may be potential σ2-selective radiotracers for imaging the proliferative status of solid tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzamides / chemical synthesis*
  • Benzamides / metabolism
  • Cell Line, Tumor
  • Guinea Pigs
  • Ligands
  • Mice
  • Molecular Conformation
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / metabolism*
  • Sigma-1 Receptor
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / metabolism

Substances

  • Benzamides
  • Ligands
  • Receptors, sigma
  • Triazoles
  • sigma-2 receptor