发现 ADX-47273 型 mGlu5 PAM 骨架内的分子开关，这些开关调节药理学模式，从而产生强效的 mGlu5 NAMs、PAMs 和部分拮抗剂。
Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists.
机构信息
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2011 May 1;21(9):2711-4. doi: 10.1016/j.bmcl.2010.11.119. Epub 2010 Dec 3.
Abstract
This Letter describes a chemical lead optimization campaign directed at a weak mGlu(5) NAM discovered while developing SAR for the mGlu(5) PAM, ADX-47273. An iterative parallel synthesis effort discovered multiple, subtle molecular switches that afford potent mGlu(5) NAMs, mGlu(5) PAMs as well as mGlu(5) partial antagonists.
摘要
这封信描述了一个针对在开发 mGlu(5) PAM（ADX-47273）的 SAR 过程中发现的弱 mGlu(5) NAM 进行的化学先导优化活动。通过迭代平行合成，发现了多个细微的分子开关，这些开关提供了有效的 mGlu(5) NAMs、mGlu(5) PAMs 以及 mGlu(5)部分拮抗剂。
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