Synthesis and biological evaluation of 4'-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists

Bioorg Med Chem. 2012 Aug 1;20(15):4661-7. doi: 10.1016/j.bmc.2012.06.011. Epub 2012 Jun 15.

Abstract

A series of 4'-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT(1) and endothelin ET(A) receptors (AT(1) IC(50)=8.5, ET(A) IC(50)=8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure-activity relationships were also discussed in the present paper.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin Receptor Antagonists / chemical synthesis*
  • Angiotensin Receptor Antagonists / pharmacology*
  • Animals
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / chemistry*
  • Benzimidazoles / pharmacology*
  • CHO Cells
  • Cricetinae
  • Endothelin A Receptor Antagonists*
  • Humans
  • Male
  • Molecular Structure
  • Rats
  • Rats, Inbred SHR
  • Receptors, Angiotensin / metabolism*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • 4'-((benzimidazole-1-yl)methyl)biphenyl-2-sulfonamide
  • Angiotensin Receptor Antagonists
  • Benzimidazoles
  • Endothelin A Receptor Antagonists
  • Receptors, Angiotensin
  • Sulfonamides