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

• 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-methylamine
• 英文别名: [(1-benzyl-1H-1,2,3-triazol-4-yl)methyl](methyl)amine；1-(1-benzyltriazol-4-yl)-N-methylmethanamine
• 化学式: C₁₁H₁₄N₄
• 分子量: 202.259
• InChiKey: NXLSEHFZPXPPKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-methylamine 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-methylamine hydrochloride
  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
• 作为产物：
  描述：

  N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-(tert-butoxycarbonyl)-N-methylamine 在 磷酸 作用下， 以 二氯甲烷 为溶剂， 以87%的产率得到N-[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]-N-methylamine
  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

• 5,5′-Bistriazoles as axially chiral, multidentate ligands: synthesis, configurational stability and catalytic application of their scandium(<scp>iii</scp>) complexes
  作者：Pablo Etayo、Eduardo C. Escudero-Adán、Miquel A. Pericàs

  DOI：10.1039/c7cy01518f

  日期：——

  chirality of these atropisomeric heterobiaryl compounds has been evidenced through structural characterization in solution and confirmed in the solid state by means of SCXRD analysis. A dinuclear stepwise mechanism for the tandem CuAACoxidative dimerization process giving rise to the bistriazole products has been tentatively proposed. The first experimental determination of the configurational stability

  讨论了具有氨基甲基取代基的5,5'-双三唑的设计和开发。从市售的炔丙基胺衍生物和叠氮化苄中选择性制备4,4'-双（氨基甲基）-5,5'-双三唑的有效合成工艺已得到优化。这些阻转异构的杂联芳基化合物的轴向手性已通过溶液中的结构表征得到证明，并通过SCXRD分析以固态得以证实。初步提出了串联的CuAAC氧化二聚过程中产生双三唑产物的双核逐步机理。基于旋转能垒和半衰期，首次实验确定了5,5'-双三唑的构型稳定性。对于仅具有轴向手性的双三唑，观察到快速消旋，而具有轴向和中心手性的更重取代的双三唑被证明是构型稳定的。通过使用N，N-二甲基炔丙基胺衍生的5,5'-双三唑作为多齿配体来控制在select（III）催化的吲哚亲核加成反应中的产物选择性（单次或两次加成），已成功实现了催化应用。伊斯兰亲电试剂。
• 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.