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.
Renren Bai  1 ,  Zhen Wei ,  Jie Liu ,  Weijia Xie ,  Hequan Yao ,  Xiaoming Wu ,  Jieyun Jiang ,  Qiujuan Wang ,  Jinyi Xu
Affiliations
  • 1. Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
PMID: 22750010 DOI: 10.1016/j.bmc.2012.06.011
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.