5-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-2-fluorobenzoic acid | 1609477-36-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-2-fluorobenzoic acid
• 英文别名: 5-[4-[4-(3,3-Dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-2-fluorobenzoic acid；5-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-2-fluorobenzoic acid
• CAS: 1609477-36-2
• 化学式: C₂₄H₂₉FO₆
• 分子量: 432.489
• InChiKey: CWZPRSAZWABAER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-2-fluorobenzoic acid 、 二甲胺 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 5-[4-[4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy]butoxy]-2-fluoro-N,N-dimethylbenzamide
  参考文献：
  名称：

  II 组代谢型谷氨酸受体的正变构调节剂 (PAM)：作为离体工具化合物的设计、合成和评估

  摘要：

  这封信描述了在铊通量测定中具有中等 mGlu 3效力和强大 mGlu 2效力的两个系列双 mGlu 2 /mGlu 3正变构调节剂的合成和评估。通过共同应用选择性mGlu 2 NAM 以分离mGlu 3选择性作用，分析了这些化合物调节中枢神经元中mGlu 3介导的信号传导的能力。利用从前额皮质急性小鼠脑切片，组II组mGlu受体激动剂的Ca的增强2+在PFC锥体细胞与双组mGlu信令2 /组mGlu 3 PAM 16E或图23d证明了通过mGlu 3选择性介导的效果。

  DOI：

  10.1016/j.bmcl.2021.128342
• 作为产物：
  描述：

  3,3-二甲基-1-丁酸 在 aluminum (III) chloride 、 草酰氯 、 potassium carbonate 、 potassium iodide 、 potassium hydroxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 24.25h， 生成 5-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-2-fluorobenzoic acid
  参考文献：
  名称：

  Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu_2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence

  摘要：

  As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu(2) receptor PAMs and no activity at mGlu(3). Compound optimization led to the identification of potent mGlu(2/3) selective PAMs with no in vitro activity at mGlu(1,4-8) or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu(2) and PAM activity at mGlu(3). The most potent mGlu(2/3) PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu(2/3) PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu(2/3) receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.

  DOI：

  10.1021/jm5000563

文献信息

• [EN] METABOTROPIC GLUTAMATE RECEPTOR POSITIVE ALLOSTERIC MODULATORS (PAMS) AND USES THEREOF<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS (PAM) DU RÉCEPTEUR MÉTABOTROPIQUE DU GLUTAMATE ET LEURS UTILISATIONS
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2015157187A1

  公开（公告）日：2015-10-15

  Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

  本文件提供了小分子活性的代谢型谷氨酸亚型-2和-3受体正变构调节剂（PAMS），包括这些化合物的组合物，以及使用这些化合物和包含这些化合物的组合物的方法。
• Metabotropic glutamate receptor positive allosteric modulators (PAMS) and uses thereof
  申请人：Sanford-Burnham Medical Research Institute

  公开号：US10099993B2

  公开（公告）日：2018-10-16

  Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

  本文提供了小分子活性代谢型谷氨酸亚型-2 和-3 受体正异位调节剂（PAMS）、包含这些化合物的组合物以及使用这些化合物和包含这些化合物的组合物的方法。
• Metabotropic Glutamate Receptor Positive Allosteric Modulators (PAMS) and Uses Thereof
  申请人：Sanford-Burnham Medical Research Institute

  公开号：US20170036987A1

  公开（公告）日：2017-02-09

  Provided herein are small molecule active metabotropic glutamate subtype-2 and -3 receptor positive allosteric modulators (PAMS), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
• Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu_2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence
  作者：Raveendra-Panickar Dhanya、Douglas J. Sheffler、Russell Dahl、Melinda Davis、Pooi San Lee、Li Yang、Hilary Highfield Nickols、Hyekyung P. Cho、Layton H. Smith、Manoranjan S. D’Souza、P. Jeffrey Conn、Andre Der-Avakian、Athina Markou、Nicholas D. P. Cosford

  DOI：10.1021/jm5000563

  日期：2014.5.22

  As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu(2) receptor PAMs and no activity at mGlu(3). Compound optimization led to the identification of potent mGlu(2/3) selective PAMs with no in vitro activity at mGlu(1,4-8) or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu(2) and PAM activity at mGlu(3). The most potent mGlu(2/3) PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu(2/3) PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu(2/3) receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
• Positive allosteric modulators (PAMs) of the group II metabotropic glutamate receptors: Design, synthesis, and evaluation as ex-vivo tool compounds
  作者：Yousuke Yamada、Kristen Gilliland、Zixiu Xiang、Daniel Haymer、Katherine E. Crocker、Matthew T. Loch、Michael L. Schulte、Alice L. Rodriguez、Colleen M. Niswender、P. Jeffrey Conn、Craig W. Lindsley、Bruce J. Melancon

  DOI：10.1016/j.bmcl.2021.128342

  日期：2021.10

  This letter describes synthesis and evaluation of two series of dual mGlu2/mGlu3 positive allosteric modulators with moderate mGlu3 potency and robust mGlu2 potency in thallium flux assays. These compounds were profiled their ability to modulate mGlu3-mediated signaling in central neurons by co-application of a selective mGlu2 NAM to isolate mGlu3-selective effects. Using acute mouse brain slices from

  这封信描述了在铊通量测定中具有中等 mGlu 3效力和强大 mGlu 2效力的两个系列双 mGlu 2 /mGlu 3正变构调节剂的合成和评估。通过共同应用选择性mGlu 2 NAM 以分离mGlu 3选择性作用，分析了这些化合物调节中枢神经元中mGlu 3介导的信号传导的能力。利用从前额皮质急性小鼠脑切片，组II组mGlu受体激动剂的Ca的增强2+在PFC锥体细胞与双组mGlu信令2 /组mGlu 3 PAM 16E或图23d证明了通过mGlu 3选择性介导的效果。