5-[(2-methyl-4-thiazolyl)ethynyl]-1H-pyridin-2-one | 878018-91-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-[(2-methyl-4-thiazolyl)ethynyl]-1H-pyridin-2-one
• 英文别名: 5-[2-(2-methyl-1,3-thiazol-4-yl)ethynyl]-1H-pyridin-2-one
• CAS: 878018-91-8
• 化学式: C₁₁H₈N₂OS
• 分子量: 216.263
• InChiKey: GTSCXUJEKILSBG-UHFFFAOYSA-N

物化性质

• 沸点：
  417.7±45.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-[(2-methyl-4-thiazolyl)ethynyl]-1H-pyridin-2-one 在 三氯氧磷 作用下， 反应 1.5h， 以62%的产率得到2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine Analogues as Potent, Noncompetitive Metabotropic Glutamate Receptor Subtype 5 Antagonists; Search for Cocaine Medications

  摘要：

  Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.

  DOI：

  10.1021/jm050570f
• 作为产物：
  描述：

  2-甲基-4-三甲基硅乙炔基噻唑 在 四丁基氟化铵 氢氧化钾 、 copper(l) iodide 、 四(三苯基膦)钯 、 氢溴酸 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.25h， 生成 5-[(2-methyl-4-thiazolyl)ethynyl]-1H-pyridin-2-one
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine Analogues as Potent, Noncompetitive Metabotropic Glutamate Receptor Subtype 5 Antagonists; Search for Cocaine Medications

  摘要：

  Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.

  DOI：

  10.1021/jm050570f

文献信息

• PHARMACOLOGICAL MODULATION OF POSITIVE AMPA RECEPTOR MODULATOR EFFECTS ON NEUROTROPHIN EXPRESSION
  申请人：The Regents of the University of California

  公开号：EP2010174A2

  公开（公告）日：2009-01-07
• [EN] PHARMACOLOGICAL MODULATION OF POSITIVE AMPA RECEPTOR MODULATOR EFFECTS ON NEUROTROPHIN EXPRESSION<br/>[FR] MODULATION PHARMACOLOGIQUE DES EFFETS POSITIFS DES MODULATEURS DES RÉCEPTEURS AMPA SUR L'EXPRESSION DE NEUROTROPHINES
  申请人：UNIV CALIFORNIA

  公开号：WO2007124348A2

  公开（公告）日：2007-11-01

  [EN] Antagonists of group 1 metabotropic glutamate receptors (mGluR) potentiate the effect of positive AMPA receptor modulators on neurotrophin expression, such as brain-derived neurotrophic factor (BDNF). The findings described herein suggest a combinatorial approach for drug therapies, using both positive AMPA receptor modulators and mGluR antagonists, to enhance brain neurotrophism.
  [FR] Selon l'invention, les antagonistes des récepteurs métabotropiques du glutamate (mGluR) du groupe 1 potentialisent l'effet positif des modulateurs des récepteurs AMPA sur l'expression de neurotrophines telles que le facteur neurotrophique dérivé du cerveau (BDNF). Les découvertes décrites dans la présente invention suggèrent pour les thérapies médicamenteuses une approche combinatoire utilisant à la fois des modulateurs positifs des récepteurs AMPA et des antagonistes des récepteurs mGluR pour renforcer le neurotropisme cérébral.
• Synthesis and Structure−Activity Relationships of 3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]pyridine Analogues as Potent, Noncompetitive Metabotropic Glutamate Receptor Subtype 5 Antagonists; Search for Cocaine Medications
  作者：Yasuyoshi Iso、Ewa Grajkowska、Jarda T. Wroblewski、Jared Davis、Nicholas E. Goeders、Kenneth M. Johnson、Subramaniam Sanker、Bryan L. Roth、Werner Tueckmantel、Alan P. Kozikowski

  DOI：10.1021/jm050570f

  日期：2006.2.1

  Recent genetic and pharmacological studies have suggested that the metabotropic glutamate receptor subtype 5 (mGluR5) may represent a druggable target in identifying new therapeutics for the treatment of various central nervous system disorders including drug abuse. In particular, considerable attention in the mGluR5 field has been devoted to identifying ligands that bind to the allosteric modulatory site, distinct from the site for the primary agonist glutamate. Both 2-methyl-6-(phenylethynyl)pyridine (MPEP) and its analogue 3-[(2-methyl-4-thiazolyl)ethynyl]pyridine (MTEP) have been shown to be selective and potent noncompetitive antagonists of mGluR5. Because of results presented in this study showing that MTEP prevents the reinstatement of cocaine self-administration caused by the presentation of environmental cues previously associated with cocaine availability, we have prepared a series of analogues of MTEP with the aim of gaining a better understanding of the structural features relevant to its antagonist potency and with the ultimate aim of investigating the effects of such compounds in blunting the self-administration of cocaine. These efforts have led to the identification of compounds showing higher potency as mGluR5 antagonists than either MPEP or MTEP. Two compounds 19 and 59 exhibited functional activity as mGluR5 antagonists that are 490 and 230 times, respectively, better than that of MTEP.