Triazolyl azabicyclo[3.1.0]hexanes: A class of potent and selective dopamine D(3) receptor antagonists

ChemMedChem. 2010 May 3;5(5):705-15. doi: 10.1002/cmdc.201000026.

Abstract

Herein we report a detailed description of the structure-activity relationships for a novel series of "C-linked" 1,2,4-triazolylazabicyclo[3.1.0]hexanes. These derivatives are endowed with very high in vitro affinity and selectivity for the dopamine D(3) receptor. An optimization with respect to undesired affinity toward the hERG potassium channel is also reported. Members of this compound series also show excellent in vitro and in vivo pharmacokinetic properties.

MeSH terms

  • Animals
  • Aza Compounds / chemistry*
  • Binding Sites
  • Bridged Bicyclo Compounds / chemistry*
  • Computer Simulation
  • Hexanes / chemical synthesis
  • Hexanes / chemistry*
  • Hexanes / pharmacokinetics
  • Humans
  • Rats
  • Receptors, Dopamine D3 / antagonists & inhibitors*
  • Receptors, Dopamine D3 / metabolism
  • Structure-Activity Relationship
  • Triazoles / chemistry*

Substances

  • Aza Compounds
  • Bridged Bicyclo Compounds
  • Hexanes
  • Receptors, Dopamine D3
  • Triazoles