N-(3-bromobenzyl)-N-methylprop-2-yn-1-amine | 138591-66-9

• 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: N-(3-bromobenzyl)-N-methylprop-2-yn-1-amine
• 英文别名: N-[(3-bromophenyl)methyl]-N-methylprop-2-yn-1-amine
• CAS: 138591-66-9
• 化学式: C₁₁H₁₂BrN
• 分子量: 238.127
• InChiKey: BENCDTCTOKFXTR-UHFFFAOYSA-N

物化性质

• 沸点：
  287.0±20.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  N-甲基炔丙基胺 、 间溴苯甲醛 在 盐酸 、 sodium cyanoborohydride 作用下， 生成 N-(3-bromobenzyl)-N-methylprop-2-yn-1-amine
  参考文献：
  名称：

  Synthesis, Biological Evaluation and Quantitative Structure Activity Relationship Analysis of Nuclear-substituted Pargylines as Competitive Inhibitors of MAO-A and MAO-B

  摘要：

  一系列取代核素的帕吉林衍生物已经制备并在受控条件下进行了测试（旨在测量竞争性抑制的成分），作为 MAO-A 和 -B 的竞争性抑制剂。只有当考虑 m- 和 p- 取代衍生物时才能获得生物数据与取代基团的物理化学常数之间的充分相关性。当抑制 MAO-B 时，p- 取代衍生物显示的活性范围较窄，未找到有意义的相关性。然而，通过 m- 取代衍生物对 MAO-B 的抑制需要包括 Verloop L 参数以获得充分的相关性，这表明 MAO-B 的抑制剂结合位点位于比 MAO-A 表面上的尺寸更有限的空腔内。对 MAO-A 和 -B 的抑制表明，抑制活性与 π 之间存在抛物线关系。虽然这种抛物线关系对于 MAO-A 的抑制显示出最大值（平均 πo = 0·86），但对于 MAO-B 的抑制却显示出最小值的 π 值（πmin= −0·5），即尚未达到 MAO-B 抑制的最佳 π 值，但对于这一系列化合物而言，该值将大于 MAO-A 的值。 Hammett σ 函数仅在 p- 取代衍生物抑制 MAO-A 时才显得重要或显著。

  DOI：

  10.1111/j.2042-7158.1991.tb03476.x

文献信息

• Synthesis, Biological Evaluation and Quantitative Structure Activity Relationship Analysis of Nuclear-substituted Pargylines as Competitive Inhibitors of MAO-A and MAO-B
  作者：Anmar Ali、J B Robinson

  DOI：10.1111/j.2042-7158.1991.tb03476.x

  日期：2011.4.12

  A series of nuclear substituted derivatives of pargyline has been prepared and tested (under controlled conditions designed to measure the competitive component of the inhibition) as competitive inhibitors of MAO-A and -B. Adequate correlation of the biological data with the physicochemical constants of substituent groups was obtained only when the m- and p-substituted derivatives were considered separately. Due to the narrow range of activity displayed by the p-substituted derivates when inhibiting MAO-B, meaningful correlations were not found. However, the inhibition of MAO-B by the m-substituted derivatives required the inclusion of the Verloop L parameter for adequate correlation, suggesting that the inhibitor binding site of MAO-B is present within a cavity of more limited lateral dimensions than that present on the MAO-A surface. Inhibition of both MAO-A and -B demonstrated a parabolic relationship between inhibitory activity and π. Whereas this parabolic relationship showed a maximal value for inhibition of MAO-A (mean πo = 0·86), inhibition of MAO-B demonstrated a minimal value of π (πmin= −0·5) i.e. the optimal value of π for inhibition of MAO-B has not been achieved for this series of compounds but such would be greater than that demonstrated for MAO-A. The Hammett σ function was important or significant only in the inhibition of MAO-A by the p-substituted derivatives.

  一系列取代核素的帕吉林衍生物已经制备并在受控条件下进行了测试（旨在测量竞争性抑制的成分），作为 MAO-A 和 -B 的竞争性抑制剂。只有当考虑 m- 和 p- 取代衍生物时才能获得生物数据与取代基团的物理化学常数之间的充分相关性。当抑制 MAO-B 时，p- 取代衍生物显示的活性范围较窄，未找到有意义的相关性。然而，通过 m- 取代衍生物对 MAO-B 的抑制需要包括 Verloop L 参数以获得充分的相关性，这表明 MAO-B 的抑制剂结合位点位于比 MAO-A 表面上的尺寸更有限的空腔内。对 MAO-A 和 -B 的抑制表明，抑制活性与 π 之间存在抛物线关系。虽然这种抛物线关系对于 MAO-A 的抑制显示出最大值（平均 πo = 0·86），但对于 MAO-B 的抑制却显示出最小值的 π 值（πmin= −0·5），即尚未达到 MAO-B 抑制的最佳 π 值，但对于这一系列化合物而言，该值将大于 MAO-A 的值。 Hammett σ 函数仅在 p- 取代衍生物抑制 MAO-A 时才显得重要或显著。
• A fragment-like approach to PYCR1 inhibition
  作者：Kirsty Milne、Jianhui Sun、Esther A. Zaal、Jenna Mowat、Patrick H.N. Celie、Alexander Fish、Celia R. Berkers、Giuseppe Forlani、Fabricio Loayza-Puch、Craig Jamieson、Reuven Agami

  DOI：10.1016/j.bmcl.2019.07.047

  日期：2019.9

  Pyrroline-5-carboxylate reductase 1 (PYCR1) is the final enzyme involved in the biosynthesis of proline and has been found to be upregulated in various forms of cancer. Due to the role of proline in maintaining the redox balance of cells and preventing apoptosis, PYCR1 is emerging as an attractive oncology target. Previous PYCR1 knockout studies led to a reduction in tumor growth. Accordingly, a small molecule inhibitor of PYCR1 could lead to new treatments for cancer, and a focused screening effort identified pargyline as a fragment-like hit. We report the design and synthesis of the first tool compounds as PYCR1 inhibitors, derived from pargyline, which were assayed to assess their ability to attenuate the production of proline. Structural activity studies have revealed the key determinants of activity, with the most potent compound (4) showing improved activity in vitro in enzyme (IC50 = 8.8 mu M) and pathway relevant effects in cell-based assays.