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设计、合成及芳基甲基哌啶类化合物作为 Kv1.5 钾通道抑制剂的生物学评价。

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

机构信息

Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China.

Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, China.

出版信息

J Enzyme Inhib Med Chem. 2022 Dec;37(1):462-471. doi: 10.1080/14756366.2021.2018683.

DOI:10.1080/14756366.2021.2018683
PMID:35012386
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8757610/
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 were synthesised and evaluated for their ability to inhibit Kv1.5 channel. Among them, compound showed good inhibitory activity (IC = 0.72 μM), preferable anti-arrhythmic effects and favoured safety. These results indicate that can be a promising Kv1.5 inhibitor for further studies.

摘要

Kv1.5 钾通道由 KCNA5 编码，是治疗心房颤动（常见心律失常之一）的有前途的靶点。基于 合成并评价了一系列新的芳基甲基哌啶衍生物，以评估它们抑制 Kv1.5 通道的能力。其中，化合物 表现出良好的抑制活性（IC = 0.72 μM）、较好的抗心律失常作用和有利的安全性。这些结果表明 可以成为进一步研究的有前途的 Kv1.5 抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/f0bd080cce9a/IENZ_A_2018683_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/5d7b06054cf3/IENZ_A_2018683_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/22475c2a221f/IENZ_A_2018683_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/286f6dba8a15/IENZ_A_2018683_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/07e80c831ddb/IENZ_A_2018683_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/012d07d6569a/IENZ_A_2018683_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/faf9e86acb15/IENZ_A_2018683_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/5fae6eff78bd/IENZ_A_2018683_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/f0bd080cce9a/IENZ_A_2018683_F0006_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/5d7b06054cf3/IENZ_A_2018683_UF0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/22475c2a221f/IENZ_A_2018683_F0001_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/286f6dba8a15/IENZ_A_2018683_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/07e80c831ddb/IENZ_A_2018683_SCH0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/012d07d6569a/IENZ_A_2018683_SCH0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/faf9e86acb15/IENZ_A_2018683_F0004_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/5fae6eff78bd/IENZ_A_2018683_F0005_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa37/8757610/f0bd080cce9a/IENZ_A_2018683_F0006_C.jpg

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本文引用的文献

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