Benzoyl and/or benzyl substituted 1,2,3-triazoles as potassium channel activators. VIII

Eur J Med Chem. 2005 Jun;40(6):521-8. doi: 10.1016/j.ejmech.2005.01.010. Epub 2005 Mar 3.

Abstract

This paper reports the preparation of new benzoyl and/or benzyl substituted 1,2,3-triazole derivatives and their pharmacological evaluation as potential BK channel openers, as a part of a research program which hypothesized a pharmacophoric structure containing the 1,2,3-triazole ring. The synthetic procedures consist essentially with the 1,3-dipolar cycloaddition of aryl or benzyl azides to the asymmetric alkyne benzoylacetylene to give the wished 4-benzoyl-1,2,3-triazole isomers in larger amount. The pharmacological results show that the 1-(2-hydroxybenzyl)-4-benzyl-1H-1,2,3-triazole possesses high vasorelaxing activity involving the opening of the BK channels. Therefore the structure-activity relationships concerning this pharmacophoric structure confirm the usefulness of a phenolic function in the ortho position of the aromatic ring and would suggest a 1,2,3-triazole model bearing benzyl substituents. In addition such substituents appear more flexible and able to take different conformations with respect to phenyl groups which have higher trend to coplanar conformations.

MeSH terms

  • Animals
  • Aorta / physiology
  • Benzoates / chemical synthesis*
  • Benzoates / chemistry
  • Benzoates / pharmacology*
  • Benzyl Compounds / chemical synthesis*
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / pharmacology*
  • Large-Conductance Calcium-Activated Potassium Channels
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Potassium Channels, Calcium-Activated / drug effects*
  • Rats
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • Vasodilator Agents / chemical synthesis
  • Vasodilator Agents / chemistry
  • Vasodilator Agents / pharmacology

Substances

  • Benzoates
  • Benzyl Compounds
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Triazoles
  • Vasodilator Agents