朝向代谢型谷氨酸受体 5 型（mGluR5）的正变构调节剂的进展。
Progress toward positive allosteric modulators of the metabotropic glutamate receptor subtype 5 (mGluR5).
机构信息
Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, USA.
出版信息
ACS Chem Neurosci. 2011 Aug 17;2(8):450-70. doi: 10.1021/cn2000519. Epub 2011 Jun 27.
Abstract
This Review describes recent trends in the development of small molecule mGlu(5) positive allosteric modulators (PAMs). A large body of pharmacological, genetic, electrophysiological, and in vivo behavioral evidence has accumulated over the past decade which continues to support the hypothesis and rationale for the activation of the metabotropic glutamate receptor subtype 5 (mGlu(5)) as a viable and promising target for the development of novel antipsychotics. Until recently, functionally efficacious and potent mGlu(5) PAMs have been somewhat structurally limited in scope and slow to emerge. This Review will discuss efforts since late 2008 which have provided novel mGlu(5) PAM chemotypes, offering ligands with a diverse range of pharmacological, physicochemical, and DMPK properties that were previously unavailable. In addition, significant biological studies of importance in the past few years using the well established PAMs known as DFB, CPPHA, CDPPB, and ADX-47273 will be discussed.
摘要
这篇综述描述了小分子 mGlu(5) 正变构调节剂 (PAMs) 的最新发展趋势。在过去的十年中，积累了大量的药理学、遗传学、电生理学和体内行为学证据，这些证据不断支持这样一种假说和基本原理，即激活代谢型谷氨酸受体亚型 5 (mGlu(5)) 作为开发新型抗精神病药物的一个可行和有前途的靶点。直到最近，在功能上有效的和有效的 mGlu(5) PAMs 在结构上有些局限，而且出现得很慢。这篇综述将讨论自 2008 年底以来的努力，这些努力提供了新型的 mGlu(5) PAM 化学型，提供了以前无法获得的具有广泛药理学、物理化学和 DMPK 性质的配体。此外，还将讨论过去几年中使用已知的 PAMs，如 DFB、CPPHA、CDPPB 和 ADX-47273 进行的重要生物学研究。
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