Design and bio-evaluation of indole derivatives as potent Kv1.5 inhibitors.
作者： Xiaoke Guo , Qian Yang , Jing Xu , Li Zhang , Hongxi Chu
DOI: 10.1016/J.BMC.2013.08.041
关键词:
摘要: Atrial fibrillation (AF) is one of the common arrhythmias that threaten human health. Kv1.5 potassium channel reported as an efficacious and safe target for treatment AF. In this paper, we designed synthesized three series compounds through modifying lead compound RH01617 was screened out by pharmacophore model earlier. All were evaluated whole-patch lamp technology most them possessed potent inhibitory activities against Kv1.5. Compounds IIIi IIIl selectivity well pharmacodynamic effects in isolated rat model. Due to promising pharmacological behavior, deserves further pharmacokinetic evaluations.
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sci-hub.se 参考文章(39)
Q Tang, Z-Q Li, W Li, J Guo, H-Y Sun, X-H Zhang, C-P Lau, H-F Tse, S Zhang, G-R Li, The 5-HT2 antagonist ketanserin is an open channel blocker of human cardiac ether-à-go-go-related gene (hERG) potassium channels. British Journal of Pharmacology. ,vol. 155, pp. 365- 373 ,(2009) , 10.1038/BJP.2008.261
Jia Guo, Sheng-Na Han, Jin-Xu Liu, Xiang-Mei Zhang, Zhen-Sheng Hu, Jie Shi, Li-Rong Zhang, Zhong-Zhong Zhao, Zhao Zhang, The Action of a Novel Fluoroquinolone Antibiotic Agent Antofloxacin Hydrochloride on Human-Ether-à-go-go-Related Gene Potassium Channel Basic & Clinical Pharmacology & Toxicology. ,vol. 107, pp. 643- 649 ,(2010) , 10.1111/J.1742-7843.2010.00550.X
John Lloyd, Heather J. Finlay, Karnail Atwal, Alexander Kover, Joseph Prol, Lin Yan, Rao Bhandaru, Wayne Vaccaro, Tram Huynh, Christine S. Huang, MaryLee Conder, Tonya Jenkins-West, Huabin Sun, Danshi Li, Paul Levesque, Dihydropyrazolopyrimidines containing benzimidazoles as KV1.5 potassium channel antagonists Bioorganic & Medicinal Chemistry Letters. ,vol. 19, pp. 5469- 5473 ,(2009) , 10.1016/J.BMCL.2009.07.083
João F. S. Carvalho, Julien Louvel, Maarten L. J. Doornbos, Elisabeth Klaasse, Zhiyi Yu, Johannes Brussee, Adriaan P. IJzerman, Strategies to reduce HERG K+ channel blockade. Exploring heteroaromaticity and rigidity in novel pyridine analogues of dofetilide. Journal of Medicinal Chemistry. ,vol. 56, pp. 2828- 2840 ,(2013) , 10.1021/JM301564F
Wayne Vaccaro, Tram Huynh, John Lloyd, Karnail Atwal, Heather J. Finlay, Paul Levesque, Mary Lee Conder, Tonya Jenkins-West, Hong Shi, Lucy Sun, Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur) Bioorganic & Medicinal Chemistry Letters. ,vol. 18, pp. 6381- 6385 ,(2008) , 10.1016/J.BMCL.2008.10.099
Kazuto YAZAWA, Muneshige KAIBARA, Masahiro OHARA, Masaki KAMEYAMA, An improved method for isolating cardiac myocytes useful for patch-clamp studies. Japanese Journal of Physiology. ,vol. 40, pp. 157- 163 ,(1990) , 10.2170/JJPHYSIOL.40.157
Minyong Li, Ying-Ju Huang, Phang C. Tai, Binghe Wang, Discovery of the first SecA inhibitors using structure-based virtual screening. Biochemical and Biophysical Research Communications. ,vol. 368, pp. 839- 845 ,(2008) , 10.1016/J.BBRC.2008.01.135
Pier Giovanni Baraldi, Delia Preti, Mojgan Aghazadeh Tabrizi, Francesca Fruttarolo, Giulia Saponaro, Stefania Baraldi, Romeo Romagnoli, Allan R Moorman, Stefania Gessi, Katia Varani, Pier Andrea Borea, None, N6-[(Hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5′-N-ethylcarboxamido-adenosines: The first example of adenosine-related structures with potent agonist activity at the human A2B adenosine receptor Bioorganic & Medicinal Chemistry. ,vol. 15, pp. 2514- 2527 ,(2007) , 10.1016/J.BMC.2007.01.055
Sham M. Sondhi, Monica Dinodia, Ashok Kumar, Synthesis, anti-inflammatory and analgesic activity evaluation of some amidine and hydrazone derivatives. Bioorganic & Medicinal Chemistry. ,vol. 14, pp. 4657- 4663 ,(2006) , 10.1016/J.BMC.2006.02.014
Qian Yang, Xiaojian Wang, Lupei Du, Minyong Li, Qidong You, Strategies for atrial fibrillation therapy: focusing on IKur potassium channel Expert Opinion on Therapeutic Patents. ,vol. 17, pp. 1443- 1456 ,(2007) , 10.1517/13543776.17.12.1443