1-苄基-N-(丙-2-炔-1-基)哌啶-4-胺 | 1019508-30-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-苄基-N-(丙-2-炔-1-基)哌啶-4-胺
• 英文名称: 1-benzyl-N-(prop-2-ynyl)aminopiperidine
• 英文别名: 1-Benzyl-N-(prop-2-YN-1-YL)piperidin-4-amine；1-benzyl-N-prop-2-ynylpiperidin-4-amine
• CAS: 1019508-30-5
• 化学式: C₁₅H₂₀N₂
• mdl: MFCD11137809
• 分子量: 228.337
• InChiKey: IPRURHXNXMQZEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.466
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(氯甲基)喹啉-8-醇 、 1-苄基-N-(丙-2-炔-1-基)哌啶-4-胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以33.8%的产率得到5-(((1-benzylpiperidin-4-yl)(prop-2-ynyl)amino)methyl)quinolin-8-ol
  参考文献：
  名称：

  Donepezil + propargylamine + 8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer's disease

  摘要：

  The synthesis, biochemical evaluation, ADMET, toxicity and molecular modeling of novel multi-target-directed Donepezil + Propargylamine + 8-Hydroxyquinoline (DPH) hybrids 1-7 for the potential prevention and treatment of Alzheimer's disease is described. The most interesting derivative was racemic α-aminotrile4-(1-benzylpiperidin-4-yl)-2-(((8-hydroxyquinolin-5-yl)methyl)(prop-2-yn-1-yl)amino) butanenitrile (DPH6) [MAO A (IC50 = 6.2 ± 0.7 μM; MAO B (IC50 = 10.2 ± 0.9 μM); AChE (IC50 = 1.8 ± 0.1 μM); BuChE (IC50 = 1.6 ± 0.25 μM)], an irreversible MAO A/B inhibitor and mixed-type AChE inhibitor with metal-chelating properties. According to docking studies, both DPH6 enantiomers interact simultaneously with the catalytic and peripheral site of EeAChE through a linker of appropriate length, supporting the observed mixed-type AChE inhibition. Both enantiomers exhibited a relatively similar position of both hydroxyquinoline and benzyl moieties with the rest of the molecule easily accommodated in the relatively large cavity of MAO A. For MAO B, the quinoline system was hosted at the cavity entrance whereas for MAO A this system occupied the substrate cavity. In this disposition the quinoline moiety interacted directly with the FAD aromatic ring. Very similar binding affinity values were also observed for both enantiomers with ChE and MAO enzymes. DPH derivatives exhibited moderate to good ADMET properties and brain penetration capacity for CNS activity. DPH6 was less toxic than donepezil at high concentrations; while at low concentrations both displayed a similar cell viability profile. Finally, in a passive avoidance task, the antiamnesic effect of DPH6 was tested on mice with experimentally induced amnesia. DPH6 was capable to significantly decrease scopolamine-induced learning deficits in healthy adult mice.

  DOI：

  10.1016/j.ejmech.2014.04.078
• 作为产物：
  描述：

  在 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 以500 mg的产率得到1-苄基-N-(丙-2-炔-1-基)哌啶-4-胺
  参考文献：
  名称：

  Donepezil + propargylamine + 8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer's disease

  摘要：

  The synthesis, biochemical evaluation, ADMET, toxicity and molecular modeling of novel multi-target-directed Donepezil + Propargylamine + 8-Hydroxyquinoline (DPH) hybrids 1-7 for the potential prevention and treatment of Alzheimer's disease is described. The most interesting derivative was racemic α-aminotrile4-(1-benzylpiperidin-4-yl)-2-(((8-hydroxyquinolin-5-yl)methyl)(prop-2-yn-1-yl)amino) butanenitrile (DPH6) [MAO A (IC50 = 6.2 ± 0.7 μM; MAO B (IC50 = 10.2 ± 0.9 μM); AChE (IC50 = 1.8 ± 0.1 μM); BuChE (IC50 = 1.6 ± 0.25 μM)], an irreversible MAO A/B inhibitor and mixed-type AChE inhibitor with metal-chelating properties. According to docking studies, both DPH6 enantiomers interact simultaneously with the catalytic and peripheral site of EeAChE through a linker of appropriate length, supporting the observed mixed-type AChE inhibition. Both enantiomers exhibited a relatively similar position of both hydroxyquinoline and benzyl moieties with the rest of the molecule easily accommodated in the relatively large cavity of MAO A. For MAO B, the quinoline system was hosted at the cavity entrance whereas for MAO A this system occupied the substrate cavity. In this disposition the quinoline moiety interacted directly with the FAD aromatic ring. Very similar binding affinity values were also observed for both enantiomers with ChE and MAO enzymes. DPH derivatives exhibited moderate to good ADMET properties and brain penetration capacity for CNS activity. DPH6 was less toxic than donepezil at high concentrations; while at low concentrations both displayed a similar cell viability profile. Finally, in a passive avoidance task, the antiamnesic effect of DPH6 was tested on mice with experimentally induced amnesia. DPH6 was capable to significantly decrease scopolamine-induced learning deficits in healthy adult mice.

  DOI：

  10.1016/j.ejmech.2014.04.078

文献信息

• 1,2, <scp>3‐Triazole</scp> analogs with bulky and conformationally rigid substructures: Synthesis and in vitro evaluation as <scp>DPP</scp> ‐4 inhibitors
  作者：Duy‐Viet Vo、Jongkook Lee、Haeil Park

  DOI：10.1002/bkcs.12677

  日期：——

  Novel 1,2,3-triazole analogs with bulky and conformationally rigid azacyclic/azabicyclic amine and alcohol substructures at the C4 position were synthesized and evaluated for their inhibitory activities against human dipeptidyl peptidase-4 enzyme. The synthesized 1,2,3-triazole analogs (2a–2f) exhibited moderate in vitro hDPP-4 inhibitory activities (0.32–>2.0 μM) in comparison to the analog with the

  新型 1,2,3-三唑类似物在 C4 位置具有大体积和构象刚性的氮杂环/氮杂双环胺和醇亚结构，并评估了它们对人二肽基肽酶 4 酶的抑制活性。与具有 C4 叔的类似物相比，合成的 1,2,3-三唑类似物 ( 2a – 2f ) 表现出适度的体外 hDPP-4 抑制活性 (0.32–>2.0 μM)-Bu 组 (0.24 μM)。然而，具有大体积和构象刚性亚结构的 1,2,3-三唑类似物的生物活性降低可能归因于引入的杂环的范德华相互作用低于预期。另一个对活性降低的合理解释可能是由于其他两个因素（π-π 相互作用和氢键）在影响类似物与酶口袋中关键氨基残基相互作用方面的作用。鼓励进一步研究探索这些因素在决定 C4 取代的 1,2,3-三唑类似物的酶抑制活性中的作用。