Triazolo and imidazo dihydropyrazolopyrimidine potassium channel antagonists

Bioorg Med Chem Lett. 2013 Mar 15;23(6):1743-7. doi: 10.1016/j.bmcl.2013.01.064. Epub 2013 Jan 26.

Abstract

Previously disclosed C6 amido and benzimidazole dihydropyrazolopyrimidines were potent and selective blockers of IKur current. Syntheses and SAR for C6 triazolo and imidazo dihydropyrazolopyrimidines series are described. Trifluoromethylcyclohexyl N(1) triazole, compound 51, was identified as a potent and selective Kv1.5 inhibitor with an acceptable PK and liability profile.

MeSH terms

  • Animals
  • Cell Line
  • Imidazoles / chemistry
  • Isomerism
  • Kv1.5 Potassium Channel / antagonists & inhibitors
  • Kv1.5 Potassium Channel / metabolism
  • Mice
  • Potassium Channel Blockers / chemical synthesis
  • Potassium Channel Blockers / chemistry*
  • Potassium Channel Blockers / metabolism
  • Potassium Channels / chemistry*
  • Potassium Channels / metabolism
  • Protein Binding
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / metabolism
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*

Substances

  • 7-(3,4-dichlorophenyl)-5-methyl-2-(trifluoromethyl)-6-(1-(4-(trifluoromethyl)cyclohexyl)-1H-1,2,4-triazol-5-yl)-4,7-dihydropyrazolo(1,5-a)pyrimidine
  • Imidazoles
  • Kv1.5 Potassium Channel
  • Potassium Channel Blockers
  • Potassium Channels
  • Pyrazoles
  • Pyrimidines
  • Triazoles
  • pyrazole
  • imidazole
  • pyrimidine