tert-butyl (3E)-3-[3-(trimethylsilyl)prop-2-yn-1-ylidene]piperidine-1-carboxylate | 1107620-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: tert-butyl (3E)-3-[3-(trimethylsilyl)prop-2-yn-1-ylidene]piperidine-1-carboxylate
• 英文别名: tert-butyl (3E)-3-(3-trimethylsilylprop-2-ynylidene)piperidine-1-carboxylate
• CAS: 1107620-57-4
• 化学式: C₁₆H₂₇NO₂Si
• 分子量: 293.481
• InChiKey: OKPFMDINUNXYFX-GXDHUFHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  20.0
• 可旋转键数：
  0.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (3E)-3-[3-(trimethylsilyl)prop-2-yn-1-ylidene]piperidine-1-carboxylate 在 copper(l) iodide 、 四(三苯基膦)钯 、 四丁基氟化铵 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基乙酰胺 为溶剂， 反应 28.25h， 生成 6-methyl-2-{(3E)-3-[3-(6-methylpyridin-2-yl)prop-2-yn-1-ylidene]piperidin-1-yl}-3-nitropyridine
  参考文献：
  名称：

  Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: Discovery and computational modeling of a new series of ligands with nanomolar affinity

  摘要：

  Metabotropic glutamate receptor 5 (mGlu(5)) is a biological target implicated in major neurological and psychiatric disorders. In the present study, we have investigated structural determinants of the interaction of negative allosteric modulators (NAMs) with the seven-transmembrane (7TM) domain of mGlu(5). A homology model of the 7TM receptor domain built on the crystal structure of the mGlu(1) template was obtained, and the binding modes of known NAMs, namely MPEP and fenobam, were investigated by docking and molecular dynamics simulations. The results were validated by comparison with mutagenesis data available in the literature for these two ligands, and subsequently corroborated by the recently described mGlu(5) crystal structure. Moreover, a new series of NAMs was synthesized and tested, providing compounds with nanomolar affinity. Several structural modifications were sequentially introduced with the aim of identifying structural features important for receptor binding. The synthesized NAMs were docked in the validated homology model and binding modes were used to interpret and discuss structure-activity relationships within this new series of compounds. Finally, the models of the interaction of NAMs with mGlu(5) were extended to include important non-aryl alkyne mGlu(5) NAMs taken from the literature. Overall, the results provide useful insights into the molecular interaction of negative allosteric modulators with mGlu(5) and may facilitate the design of new modulators for this class of receptors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.008
• 作为产物：
  描述：

  diethyl (3-(trimethylsilyl)prop-2-yn-1-yl)phosphonate 、 N-叔丁氧羰基-3-哌啶酮 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙基苯 为溶剂， 反应 3.33h， 以10%的产率得到tert-butyl (3E)-3-[3-(trimethylsilyl)prop-2-yn-1-ylidene]piperidine-1-carboxylate
  参考文献：
  名称：

  Insights into the interaction of negative allosteric modulators with the metabotropic glutamate receptor 5: Discovery and computational modeling of a new series of ligands with nanomolar affinity

  摘要：

  Metabotropic glutamate receptor 5 (mGlu(5)) is a biological target implicated in major neurological and psychiatric disorders. In the present study, we have investigated structural determinants of the interaction of negative allosteric modulators (NAMs) with the seven-transmembrane (7TM) domain of mGlu(5). A homology model of the 7TM receptor domain built on the crystal structure of the mGlu(1) template was obtained, and the binding modes of known NAMs, namely MPEP and fenobam, were investigated by docking and molecular dynamics simulations. The results were validated by comparison with mutagenesis data available in the literature for these two ligands, and subsequently corroborated by the recently described mGlu(5) crystal structure. Moreover, a new series of NAMs was synthesized and tested, providing compounds with nanomolar affinity. Several structural modifications were sequentially introduced with the aim of identifying structural features important for receptor binding. The synthesized NAMs were docked in the validated homology model and binding modes were used to interpret and discuss structure-activity relationships within this new series of compounds. Finally, the models of the interaction of NAMs with mGlu(5) were extended to include important non-aryl alkyne mGlu(5) NAMs taken from the literature. Overall, the results provide useful insights into the molecular interaction of negative allosteric modulators with mGlu(5) and may facilitate the design of new modulators for this class of receptors. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.008