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

  • J Enzyme Inhib Med Chem. 2022 Dec;37(1):462-471. doi: 10.1080/14756366.2021.2018683.
Lingyue Zhao  1  2 ,  Qian Yang  1  2 ,  Yiqun Tang  3 ,  Qidong You  1  2 ,  Xiaoke Guo  1  2
Affiliations
  • 1. Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China.
  • 2. Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
  • 3. Department of Clinical Pharmacy, School of Basic Medical Sciences and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
PMID: 35012386 DOI: 10.1080/14756366.2021.2018683
Abstract

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 (IC50 = 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.

Keywords
Kv1.5 inhibitors; anti-arrhythmia; atrial fibrillation.
Products