伪糖精胺作为强效且选择性的KV1.5阻滞剂。
Pseudosaccharin amines as potent and selective KV1.5 blockers.
作者信息
Lloyd John, Finlay Heather J, Kover Alexander, Johnson James, Pi Zulan, Jiang Ji, Neels James, Cavallaro Cullen, Wexler Ruth, Conder Mary Lee, Shi Hong, Li Danshi, Sun Huabin, Chimalakonda Anjaneya, Huang Christine, Salvati Mark, Levesque Paul
机构信息
Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08534-5400, USA.
出版信息
Bioorg Med Chem Lett. 2015 Nov 1;25(21):4983-4986. doi: 10.1016/j.bmcl.2015.02.066. Epub 2015 Mar 7.
Phenethyl aminoheterocycles like compound 1 were known to be potent I(Kur) blockers although they lacked potency in vivo. Modification of the heterocycle led to the design and synthesis of pseudosaccharin amines. Compounds such as 14, 17d and 21c were found to be potent K(V)1.5 blockers and selective over other cardiac ion channels. These compounds had potent pharmacodynamic activity, however, they also showed off-target activities such as hemodynamic effects.
像化合物1这样的苯乙胺基杂环化合物已知是有效的I(Kur)阻滞剂，尽管它们在体内缺乏效力。对杂环的修饰导致了假糖精胺的设计和合成。发现化合物14、17d和21c是有效的K(V)1.5阻滞剂，并且对其他心脏离子通道具有选择性。这些化合物具有强大的药效学活性，然而，它们也表现出诸如血流动力学效应等脱靶活性。
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