3-(2-(6-methylpyridin-2-yl)ethynyl)-5-fluorobenzonitrile | 1224431-15-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(2-(6-methylpyridin-2-yl)ethynyl)-5-fluorobenzonitrile
• 英文别名: 6-methyl-2-[(3-cyano-5-fluorophenyl)ethynyl]pyridine；MFZ 10-7；3-fluoro-5-[2-(6-methylpyridin-2-yl)ethynyl]benzonitrile
• CAS: 1224431-15-5
• 化学式: C₁₅H₉FN₂
• 分子量: 236.248
• InChiKey: ZGEXQIMQZVRTDZ-UHFFFAOYSA-N

物化性质

• 沸点：
  396.2±42.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)
• 溶解度：
  在 DMSO 中溶解度为 100 mM，在乙醇中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-(6-methylpyridin-2-yl)ethynyl)-5-fluorobenzonitrile 在 氢溴酸 作用下， 以 甲醇 为溶剂， 生成 MFZ10-7 hydrobromide
  参考文献：
  名称：

  Metabotropic Glutamate Receptor 5 Negative Allosteric Modulators as Novel Tools for in Vivo Investigation

  摘要：

  Negative allosteric modulators (NAMs) of metabotropic glutamate receptor subtype 5 (mGluR5) have shown promising results in preclinical models for anxiety and drug abuse. Here, we describe a series of aryl substituted alkynyl analogues of the prototypic mGluR5 NAM 2-methyl-6-(phenylethynyl)pyridine (MPEP, 1). Displacement of [H-3]1 binding in rat brain membranes showed that several of these novel compounds displayed high affinity binding (K-i < 10 nM) for mGluR5, with up to a 24 fold increase in affinity over 1. Replacements of the 2-position Me on the pyridyl ring of 1 along with various 3'-CN, 5'-substitutions were generally well tolerated All of the active analogues in this series had cLog P values in the 2-5 range and displayed inverse agonist characteristics in an ELISA-based assay of G(q)alpha-mediated IP3 production. Compounds 7i and 7j produced in vivo effects in mouse models of anxiety-like behaviors more potently than 1 or 3-3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP, 2), supporting their utility as in vivo tools.

  DOI：

  10.1021/ml3000726
• 作为产物：
  描述：

  2-溴-6-甲基吡啶 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 3-(2-(6-methylpyridin-2-yl)ethynyl)-5-fluorobenzonitrile
  参考文献：
  名称：

  Potent mGluR5 antagonists: Pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series

  摘要：

  We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.047

文献信息

• Iodonium Cyclophanes for SECURE Arene Functionalization
  申请人：DiMagno Stephen

  公开号：US20110190505A1

  公开（公告）日：2011-08-04

  This disclosure relates to compounds, reagents, and methods useful in the synthesis of aryl fluorides, for example, in the preparation of 18 F labeled radiotracers. For example, this disclosure provides universal “locked” aryl substituents that result in StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) from diaryliodonium salts. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.

  本公开涉及化合物、试剂和合成芳基氟化物的方法，例如在制备18F标记的放射追踪剂中。例如，本公开提供了通用的“锁定”芳基取代基，从二芳基碘盐中结果的立体电子控制单向还原消除（SECURE）。本文所提供的试剂和方法可用于访问广泛的化合物，包括芳香族化合物、杂环芳香族化合物、氨基酸、核苷酸和合成化合物。
• Fluorination of Aromatic Ring Systems
  申请人：DiMagno Stephen Gregory

  公开号：US20110313170A1

  公开（公告）日：2011-12-22

  This disclosure relates to reagents and methods useful in the synthesis of aryl fluorides, for example, in the preparation of 18 F labeled radiotracers. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.

  本公开涉及到试剂和方法，可用于合成芳基氟化物，例如制备18F标记的放射性示踪剂。本文提供的试剂和方法可用于获得广泛的化合物，包括芳香族化合物、杂环芳香族化合物、氨基酸、核苷酸和合成化合物。
• FLUORINATION OF AROMATIC RING SYSTEMS
  申请人：Dimagno Stephen

  公开号：US20120004417A1

  公开（公告）日：2012-01-05

  This disclosure relates to reagents and methods useful in the synthesis of aryl fluorides, for example, in the preparation of 18 F labeled radiotracers. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.

  本公开涉及与合成芳基氟化物有关的试剂和方法，例如，在制备18F标记的放射性示踪剂时。本文提供的试剂和方法可用于访问广泛的化合物，包括芳香族化合物，杂环芳香族化合物，氨基酸，核苷酸和合成化合物。
• Negative allosteric modulators of MGLUR5 for use in the treatment of mature brain damages
  申请人：Sinntaxis AB

  公开号：US11033545B2

  公开（公告）日：2021-06-15

  The present disclosure relates to the use of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor 5 (mGluR5) in the treatment of a mature brain damage, such as damage after stroke.

  本公开涉及代谢型谷氨酸受体 5（mGluR5）的负变构调节剂（NAMs）在治疗成熟脑损伤（如中风后的损伤）中的应用。
• Potent mGluR5 antagonists: Pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series
  作者：David Alagille、Herve DaCosta、Yelin Chen、Kamondanai Hemstapat、Alice Rodriguez、Ronald M. Baldwin、Jeffrey P. Conn、Gilles D. Tamagnan

  DOI：10.1016/j.bmcl.2011.04.047

  日期：2011.6

  We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity. (C) 2011 Elsevier Ltd. All rights reserved.