Molecular hybridization, synthesis, and biological evaluation of novel chroman IKr and IKs dual blockers

The combination of IKr and IKs 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 IKr and IKs 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.

Graphical abstractOn the rationale of molecular hybridization of azimilide and HMR-1556, a novel series of IKr and IKs dual blockers were designed, synthesized and evaluated.Figure optionsDownload full-size imageDownload as PowerPoint slide