3-Benzyl-1,3-oxazolidin-2-ones as mGluR2 positive allosteric modulators: Hit-to lead and lead optimization
3-Benzyl-1,3-oxazolidin-2-ones as mGluR2 positive allosteric modulators: Hit-to lead and lead optimization
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DOI：
10.1016/j.bmcl.2009.03.032
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发表时间：
2009-05-01
影响因子：
2.7
通讯作者：
Zhang, Lei
中科院分区：
文献类型：
--
作者：
Duplantier, Allen J.;Efremov, Ivan;Zhang, Lei
描述了作为 mGluR2 正变构调节剂 (PAM) 的一系列新型 3-benzyl-1,3-oxazolidin-2-ones 的发现、合成和 SAR。对单个 HTS 命中的便捷命中到先导工作导致了配体高效且结构有吸引力的一系列 mGluR2 PAM 的鉴定。人类微粒体清除率和初始先导物的次优理化性质得到改善，得到有效、代谢稳定且可口服的 mGluR2 PAM。 (C) 2009 Elsevier Ltd. 保留所有权利。
The discovery, synthesis and SAR of a novel series of 3-benzyl-1,3-oxazolidin-2-ones as positive allosteric modulators (PAMs) of mGluR2 is described. Expedient hit-to-lead work on a single HTS hit led to the identification of a ligand-efficient and structurally attractive series of mGluR2 PAMs. Human microsomal clearance and suboptimal physicochemical properties of the initial lead were improved to give potent, metabolically stable and orally available mGluR2 PAMs. (C) 2009 Elsevier Ltd. All rights reserved.