通过高通量筛选发现的新型 Kir6.2/SUR1 通道 opener 支架的合成及 SAR 研究。
Synthesis and SAR of a novel Kir6.2/SUR1 channel opener scaffold identified by HTS.
机构信息
Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2023 May 1;87:129256. doi: 10.1016/j.bmcl.2023.129256. Epub 2023 Mar 24.
Abstract
Kir6.2/SUR1 is an ATP-regulated potassium channel that acts as an intracellular metabolic sensor, controlling insulin and appetite-stimulatory neuropeptides secretion. In this Letter, we present the SAR around a novel Kir6.2/SUR1 channel opener scaffold derived from an HTS screening campaign. New series of compounds with tractable SAR trends and favorable potencies are reported.
摘要
Kir6.2/SUR1 是一种 ATP 调节性钾通道，作为细胞内代谢传感器，控制胰岛素和食欲刺激神经肽的分泌。在这封信中，我们介绍了源于高内涵筛选的新型 Kir6.2/SUR1 通道开放剂支架的 SAR。报道了具有可处理的 SAR 趋势和良好效力的新系列化合物。
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