从持续优化 MLPCN 探针 ML012 中开发出一种更高选择性的 M1 拮抗剂。
Development of a more highly selective M(1) antagonist from the continued optimization of the MLPCN Probe ML012.
机构信息
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2012 Jan 15;22(2):1044-8. doi: 10.1016/j.bmcl.2011.11.110. Epub 2011 Dec 6.
Abstract
This Letter describes the continued optimization of an MLPCN probe molecule (ML012) through an iterative parallel synthesis approach. After exploring extensive modifications throughout the parent structure, we arrived at a more highly M(1)-selective antagonist, compound 13l (VU0415248). Muscarinic subtype selectivity across all five human and rat receptors for 13l, along with rat selectivity for the lead compound (ML012), is presented.
摘要
这封信件描述了通过迭代平行合成方法对 MLPCN 探针分子（ML012）的持续优化。在对母体结构进行广泛修饰后，我们得到了一个更高选择性的 M(1)拮抗剂，化合物 13l（VU0415248）。文中介绍了化合物 13l 对所有五个人类和大鼠受体的毒蕈碱亚型选择性，以及对先导化合物（ML012）的大鼠选择性。
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