α-Hydroxy-N-propyldiphenylacetamide | 52839-74-4

• 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: α-Hydroxy-N-propyldiphenylacetamide
• 英文别名: N-propyl-2,2-diphenyl-2-hydroxyacetamide；N-propyl-benzilamide；Benzilsaeurepropylamid；N-Propyl-benzilamid；2-hydroxy-2,2-diphenyl-N-propylacetamide
• CAS: 52839-74-4
• 化学式: C₁₇H₁₉NO₂
• 分子量: 269.343
• InChiKey: ALYNHPLBMYWVLF-UHFFFAOYSA-N

物化性质

• 熔点：
  75-77 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  497.8±45.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  二苯乙醇酸甲酯 、 正丁胺 以 neat (no solvent) 为溶剂， 150.0 ℃ 、1.72 MPa 条件下， 反应 0.17h， 以20%的产率得到α-Hydroxy-N-propyldiphenylacetamide
  参考文献：
  名称：

  N-propyl-2,2-diphenyl-2-hydroxyacetamide, a novel α-hydroxyamide with anticonvulsant, anxiolytic and antidepressant-like effects that inhibits voltage-gated sodium channels

  摘要：

  In patients with epilepsy, anxiety and depression are the most frequent psychiatric comorbidities but they often remain unrecognized and untreated.We report herein the antidepressant-like activity in two animal models, tail suspension and forced swimming tests, of six anticonvulsants alpha-hydroxyamides. From these, N-propyl-2,2-diphenyl-2-hydroxyacetamide (compound 5) emerged not only as the most active as anticonvulsant (ED50 = 2.5 mg/kg, MES test), but it showed the most remarkable antidepressant-like effect in the tail suspension and forced swimming tests (0.3-30 mg/kg, i.p.); and, also, anxiolytic-like action in the plus maze test (3-10 mg/kg, i.p.) in mice. Studies of its mechanism of action, by means of its capacity to act via the GABA(A) receptor ([H-3]-flunitrazepam binding assay); the 5-HT1A receptor ([H-3]-8-OH-DPAT binding assay) and the voltage-gated sodium channels (either using the patch clamp technique in hNa(v) 1.2 expressed in HEK293 cell line or using veratrine, in vivo) were attempted. The results demonstrated that its effects are not likely related to 5-HT1A or GABA(A)ergic receptors and that its anticonvulsant and antidepressant-like effect could be due to its voltage-gated sodium channel blocking properties.

  DOI：

  10.1016/j.ejphar.2017.11.048

文献信息

• Synthesis of α-Hydroxycarboxamides from Acetonides of α-Hydroxycarboxylic Acids and Primary Amines
  作者：A. Khalaj、E. Nahid

  DOI：10.1055/s-1985-31460

  日期：——

  The reaction of acetonides of α-hydroxycarboxylic acids with primary amines on heating provides a useful synthetic route to N-substituted α-hydroxycarboxamides. In general, formation of the α-hydroxycarboxamides is favored by the presence of only small substituents on the acetonide, by sufficient nucleophilicity of the amine, and by high-boiling aprotic solvents.

  加热时，α-羟基羧酸的乙酰苯乙醚与初级胺反应提供了一种合成N取代的α-羟基羧酰胺的有效路线。一般而言，α-羟基羧酰胺的形成受益于乙酰苯乙醚上仅有小取代基的存在、胺的足够亲核性以及高沸点非质子溶剂。
• Curtius, Journal fur praktische Chemie (Leipzig 1954), 1917, vol. <2> 95, p. 211
  作者：Curtius

  DOI：——

  日期：——
• KHALAJ, A.;NAHID, E., SYNTHESIS, BRD, 1985, N 12, 1153-1155
  作者：KHALAJ, A.、NAHID, E.

  DOI：——

  日期：——
• N-propyl-2,2-diphenyl-2-hydroxyacetamide, a novel α-hydroxyamide with anticonvulsant, anxiolytic and antidepressant-like effects that inhibits voltage-gated sodium channels
  作者：Valentina Pastore、Cristina Wasowski、Pedro Martin、Andrea Enrique、Josefina Higgs、Luis E. Bruno-Blanch、Veronica Milesi、Mariel Marder

  DOI：10.1016/j.ejphar.2017.11.048

  日期：2018.1

  In patients with epilepsy, anxiety and depression are the most frequent psychiatric comorbidities but they often remain unrecognized and untreated.We report herein the antidepressant-like activity in two animal models, tail suspension and forced swimming tests, of six anticonvulsants alpha-hydroxyamides. From these, N-propyl-2,2-diphenyl-2-hydroxyacetamide (compound 5) emerged not only as the most active as anticonvulsant (ED50 = 2.5 mg/kg, MES test), but it showed the most remarkable antidepressant-like effect in the tail suspension and forced swimming tests (0.3-30 mg/kg, i.p.); and, also, anxiolytic-like action in the plus maze test (3-10 mg/kg, i.p.) in mice. Studies of its mechanism of action, by means of its capacity to act via the GABA(A) receptor ([H-3]-flunitrazepam binding assay); the 5-HT1A receptor ([H-3]-8-OH-DPAT binding assay) and the voltage-gated sodium channels (either using the patch clamp technique in hNa(v) 1.2 expressed in HEK293 cell line or using veratrine, in vivo) were attempted. The results demonstrated that its effects are not likely related to 5-HT1A or GABA(A)ergic receptors and that its anticonvulsant and antidepressant-like effect could be due to its voltage-gated sodium channel blocking properties.