Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA.
Bioorg Med Chem Lett. 2022 Dec 15;78:129021. doi: 10.1016/j.bmcl.2022.129021. Epub 2022 Oct 10.
This Letter describes our ongoing effort to improve the clearance of selective M antagonists. Herein, we report the replacement of the previously disclosed piperidine amide (4, disclosed in Part 1) with a pyrrolidine amide core. Several compounds within this series provided good potency, subtype selectivity, and low to moderate clearance profiles. Interestingly, the left-hand side SAR for this series diverged from our earlier efforts.
这封信描述了我们正在努力提高选择性 M 拮抗剂的清除率。在此，我们报告了先前披露的哌啶酰胺（第 1 部分中披露的 4）被吡咯烷酰胺核心取代。该系列中的几种化合物具有良好的效力、亚型选择性和低至中等的清除率特征。有趣的是，该系列的左侧 SAR 偏离了我们早期的研究。
