Design and synthesis of sulfonamidophenylethylamides as novel cardiac myosin activator

•N-Phenethyl-5-phenylpentanamides were explored as novel cardiac myosin activators.•Selective cardiac myosin ATPase activation of 13 and 27 are 48.5% and 55.0% at 10 µM.•The hemodynamic profiles of 13 and 27 in rat were greatly improved.•Potent compounds showed positive inotropic effect in isolated rat ventricular myocytes.•N,N-dimethylsulfonamide of 13 and 27 well fit into binding pocket of the enzyme.