4-chloro-1-trimethylsilyl-1-hexyn-3-one | 914358-92-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-chloro-1-trimethylsilyl-1-hexyn-3-one
• 英文别名: 4-Chloro-1-(trimethylsilyl)-1-hexyn-3-one；4-chloro-1-trimethylsilylhex-1-yn-3-one
• CAS: 914358-92-2
• 化学式: C₉H₁₅ClOSi
• 分子量: 202.756
• InChiKey: AOEYGYUEIRXWQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.45
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-chloro-1-trimethylsilyl-1-hexyn-3-one 在 四丁基氟化铵 、 四丁基碘化铵 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 生成 3-[(5-Ethyl-2-methyl-4-thiazolyl)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-氯丁酰氯 、 二(三甲基甲硅烷基)乙炔 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 生成 4-chloro-1-trimethylsilyl-1-hexyn-3-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

• 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.