N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-methyl-N-propargylamine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-methyl-N-propargylamine
• 英文别名: N-[(1-benzyltriazol-4-yl)methyl]-N-methylprop-2-yn-1-amine
• 化学式: C₁₄H₁₆N₄
• 分子量: 240.308
• InChiKey: WZCXCEOFJVMUMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  34
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  tert-butyl ((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)carbamate 在 磷酸 、 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 甲苯 、 mineral oil 为溶剂， 反应 3.0h， 生成 N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-methyl-N-propargylamine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of N-methyl-N-[(1,2,3-triazol-4-yl)alkyl]propargylamines as novel monoamine oxidase B inhibitors

  摘要：

  Different azides and alkynes have been coupled via Cu-catalyzed 1,3-dipolar Huisgen cycloaddition to afford a novel family of N-1- and C-5-substituted 1,2,3-triazole derivatives that feature the propargylamine group typical of irreversible MAO-B inhibitors at the C4-side chain of the triazole ring. All the synthesized compounds were evaluated against human MAO-A and MAO-B. Structure-activity relationships and molecular modeling were utilized to gain insight into the structural and chemical features that enhance the binding affinity and selectivity between the two enzyme isoforms. Several lead compounds, in terms of potency (submicromolar to low micromolar range), MAO-B selective recognition, and brain permeability, were identified. One of these leads (MAO-B IC50 of 3.54 mu M, selectivity MAO-A/MAO-B index of 27.7) was further subjected to reversibility and time-dependence inhibition studies, which disclosed a slow and irreversible inhibition of human MAO-B. Overall, the results support the suitability of the 4-triazolylalkyl propargylamine scaffold for exploring the design of multipotent anti-Alzheimer compounds endowed with irreversible MAO-B inhibitory activity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.06.045

文献信息

• Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions
  作者：Xiaoguang Zhang、Peiye Liu、Lei Zhu

  DOI：10.3390/molecules21121697

  日期：——

  This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as "privileged" azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under

  这项工作代表了我们为确定在铜催化的叠氮化物-炔烃环加成（CuAAC）反应中具有最佳反应性而需要的叠氮化物/炔烃对的初步工作。在以前的工作中，我们已经将螯合叠氮化物，特别是2-picolyl叠氮化物确定为具有高CuAAC反应性的“特权”叠氮化物底物。在当前的工作中，两种类型的炔烃在铜（II）-（通过诱导期）和铜（I）催化的条件下均会发生快速的CuAAC反应。第一种炔烃带有相对酸性的乙炔基CH键，而第二种炔烃则包含N-（三唑基甲基）丙炔基部分，可产生自加速作用。提供了在铜（II）-和铜（I）催化的条件下的反应性等级。关于其他反应参数如加速配体的观察
• Design, synthesis and biological evaluation of N-methyl-N-[(1,2,3-triazol-4-yl)alkyl]propargylamines as novel monoamine oxidase B inhibitors
  作者：Ornella Di Pietro、Nelson Alencar、Gerard Esteban、Elisabet Viayna、Natalia Szałaj、Javier Vázquez、Jordi Juárez-Jiménez、Irene Sola、Belén Pérez、Montse Solé、Mercedes Unzeta、Diego Muñoz-Torrero、F. Javier Luque

  DOI：10.1016/j.bmc.2016.06.045

  日期：2016.10

  Different azides and alkynes have been coupled via Cu-catalyzed 1,3-dipolar Huisgen cycloaddition to afford a novel family of N-1- and C-5-substituted 1,2,3-triazole derivatives that feature the propargylamine group typical of irreversible MAO-B inhibitors at the C4-side chain of the triazole ring. All the synthesized compounds were evaluated against human MAO-A and MAO-B. Structure-activity relationships and molecular modeling were utilized to gain insight into the structural and chemical features that enhance the binding affinity and selectivity between the two enzyme isoforms. Several lead compounds, in terms of potency (submicromolar to low micromolar range), MAO-B selective recognition, and brain permeability, were identified. One of these leads (MAO-B IC50 of 3.54 mu M, selectivity MAO-A/MAO-B index of 27.7) was further subjected to reversibility and time-dependence inhibition studies, which disclosed a slow and irreversible inhibition of human MAO-B. Overall, the results support the suitability of the 4-triazolylalkyl propargylamine scaffold for exploring the design of multipotent anti-Alzheimer compounds endowed with irreversible MAO-B inhibitory activity. (C) 2016 Elsevier Ltd. All rights reserved.