苯甲酰胺类Kv1.5钾离子通道阻滞剂的研究

doi:10.5246/jcps.2012.06.070

苯甲酰胺类Kv1.5钾离子通道阻滞剂的研究

郭小可, 沈征, 于鹏, 褚红喜, 汤依群, 尤启冬*

1. 中国药科大学药物化学教研室, 江苏南京 210009
2. 中国药科大学药理学教研室, 江苏南京 210009

收稿日期:2012-06-14 修回日期:2012-08-20 出版日期:2012-10-25 发布日期:2012-10-25
通讯作者: 尤启冬*

Discovery of benzamide derivatives as potent Kv1.5 inhibitors

Xiaoke Guo, Zheng Shen, Peng Yu, Hongxi Chu, Yiqun Tang, Qidong You*

1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China
2. Research Division of Pharmacology, China Pharmaceutical University, Nanjing 210009, China

Received:2012-06-14 Revised:2012-08-20 Online:2012-10-25 Published:2012-10-25
Contact: Qidong You*

摘要/Abstract

摘要：

文献报道Kv1.5钾离子通道为治疗心房颤动的一个安全有效的靶点。在前期研究中我们证明化合物CPUY11018有中等的抑制Kv1.5钾离子通道的作用, 但其稳定性较差。为了改善其稳定性同时为了探讨构效关系, 本文利用骨架迁越原理, 合成了4个系列共17个苯甲酰胺类衍生物并测定其Kv1.5阻滞活性。其中, 化合物8c显示出良好的Kv1.5阻滞活性。

关键词: Kv1.5, 超速延迟整流钾离子通道, 钾离子通道, 心房颤动

Abstract: Kv1.5 potassium channel is reported as a potent and safe target for atrial fibrillation. CPUY11018 was proved it had moderate inhibition of Kv1.5. In order to improve the stability of CPUY11018, and investigate the structure-activity relationship, 4 series of benzamide derivatives were synthesized and evaluated. Among them, 8c is a most potent inhibitor of Kv1.5.

Key words: Kv1.5, Ultra-rapid potassium current, Potassium channel, Atrial fibrillation

中图分类号:

R916

Supporting:

Foundation items: National High-tech R&D Program of China (863 Program, Grant No. 2007AA02Z307), National Major Science and Technology Project of China (Grant No. 2009ZX09103-088 and 2009ZX09501-003).
^*Corresponding author. Tel.: 86-25-83271351

郭小可, 沈征, 于鹏, 褚红喜, 汤依群, 尤启冬*. 苯甲酰胺类Kv1.5钾离子通道阻滞剂的研究[J]. , DOI: 10.5246/jcps.2012.06.070.

Xiaoke Guo, Zheng Shen, Peng Yu, Hongxi Chu, Yiqun Tang, Qidong You* . Discovery of benzamide derivatives as potent Kv1.5 inhibitors [J]. , DOI: 10.5246/jcps.2012.06.070.

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