Molecular hybridization, synthesis, and biological evaluation of novel chroman I(Kr) and I(Ks) dual blockers

  • Bioorg Med Chem Lett. 2009 Mar 1;19(5):1477-80. doi: 10.1016/j.bmcl.2009.01.022.
Lupei Du  1 ,  Minyong Li ,  Qian Yang ,  Yiqun Tang ,  Qidong You ,  Lin Xia
Affiliations
  • 1. Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Jiangsu 210009, China.
PMID: 19185489 DOI: 10.1016/j.bmcl.2009.01.022
Abstract

The combination of I(Kr) and I(Ks) blockade could lead to synergistic and safe class III anti-arrhythmic effect with the enhanced efficacy and reduced risk. On the rationale of structural hybridization of azimilide and HMR-1556, a novel series of I(Kr) and I(Ks) dual blockers were designed, synthesized and evaluated in vitro. One compound, 3r (CPUY11018), deserves further evaluation for its potent anti-arrhythmic activity and favorable cardiovascular profile.