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

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 AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 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.

A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia–Il) were synthesized and biologically evaluated. The most prospective compound Ig was found to have the most effective antagonism for Ang II AT1 and endothelin ETA receptors, exhibiting more potent activity (AT1 IC50 = 8.5 nM, ETA IC50 = 8.9 nM) than losartan and equivalent activity to bosentan, and was more potent than losartan in RHRs with no significant effect on heart rate.Figure optionsDownload as PowerPoint slide