发现并研究了一系列新型 GIRK1/2 和 GIRK1/4 激活剂。
Discovery and SAR of a novel series of GIRK1/2 and GIRK1/4 activators.
机构信息
Department of Chemistry, Vanderbilt University, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2013 Sep 15;23(18):5195-8. doi: 10.1016/j.bmcl.2013.07.002. Epub 2013 Jul 18.
Abstract
This Letter describes a novel series of GIRK activators identified through an HTS campaign. The HTS lead was a potent and efficacious dual GIRK1/2 and GIRK1/4 activator. Further chemical optimization through both iterative parallel synthesis and fragment library efforts identified dual GIRK1/2 and GIRK1/4 activators as well as the first examples of selective GIRK1/4 activators. Importantly, these compounds were inactive on GIRK2 and other non-GIRK1 containing GIRK channels, and SAR proved shallow.
摘要
这封信件描述了通过高通量筛选（HTS）活动鉴定出的新型 GIRK 激活剂系列。HTS 的先导化合物是一种强效且有效的双重 GIRK1/2 和 GIRK1/4 激活剂。通过迭代平行合成和片段文库工作的进一步化学优化，确定了双重 GIRK1/2 和 GIRK1/4 激活剂以及首个选择性 GIRK1/4 激活剂的例子。重要的是，这些化合物对 GIRK2 和其他非 GIRK1 包含的 GIRK 通道没有活性，并且 SAR 证明很浅显。
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