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Kv1.5 potassium channel, encoded by KCNA5, is a promising target for the treatment of atrial fibrillation, one of the common arrhythmia. A new series of arylmethylpiperidines derivatives based on  DDO-02001  were synthesised and evaluated for their ability to inhibit Kv1.5 channel. Among them, compound  DDO-02005  showed good inhibitory activity (IC 50  = 0.72 μM), preferable anti-arrhythmic effects and favoured safety. These results indicate that  DDO-02005  can be a promising Kv1.5 inhibitor for further studies.

Design, synthesis, and biological evaluation of arylmethylpiperidines as Kv1.5 potassium channel inhibitors