N'-(3-hydroxy-4-methoxybenzoyl)-3,4,5-trimethoxybenzohydrazide | 1257321-37-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: N'-(3-hydroxy-4-methoxybenzoyl)-3,4,5-trimethoxybenzohydrazide
• CAS: 1257321-37-1
• 化学式: C₁₈H₂₀N₂O₇
• 分子量: 376.366
• InChiKey: HOUFRGXJZZBBTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  115.35
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  N'-(3-hydroxy-4-methoxybenzoyl)-3,4,5-trimethoxybenzohydrazide 在 三乙胺 、 对甲苯磺酰氯 、 水 作用下， 以 二氯甲烷 、 甲醇 为溶剂， 反应 24.0h， 以2.15 g的产率得到2-(3-hydroxy-4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazole
  参考文献：
  名称：

  Synthesis of Antimitotic Polyalkoxyphenyl Derivatives of Combretastatin Using Plant Allylpolyalkoxybenzenes

  摘要：

  DOI：

  10.1021/np1004278
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酸 在 吡啶 、 氯化亚砜 、 一水合肼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 N'-(3-hydroxy-4-methoxybenzoyl)-3,4,5-trimethoxybenzohydrazide
  参考文献：
  名称：

  Synthesis of Antimitotic Polyalkoxyphenyl Derivatives of Combretastatin Using Plant Allylpolyalkoxybenzenes

  摘要：

  DOI：

  10.1021/np1004278

文献信息

• Tubulin inhibitors: Discovery of a new scaffold targeting extra-binding residues within the colchicine site through anchoring substituents properly adapted to their pocket by a semi-flexible linker
  作者：Raed M. Maklad、El-Shimaa M.N. AbdelHafez、Dalia Abdelhamid、Omar M. Aly

  DOI：10.1016/j.bioorg.2020.103767

  日期：2020.6

  Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively targeting the colchicine site between alpha- and beta-tubulin subunits. The newly designed ring-B substituents were assisted at their ends by 'anchor groups' which are expected to exert binding interaction(s) with new additional amino acid residues in the colchicine site (beyond those amino acids previously reported to interact with reference inhibitors as CA-4 and colchicine). Conformational flexibility of bis-hydrazide linker assisted these 'extra-binding' properties through reliving ligands' strains in the final ligand-receptor complexes. Compound 13f displayed the most promising computational and biological study results in the series: MM/GBSA binding energy of -62.362 kcal/mol (extra-binding to Arg a:221, Thr beta:353 & Lys beta:254); 34% NCI-H522 cells' death (at 10 mu M), IC50 = 0.073 mu M (MTT assay); significant cell cycle arrest at G2/M phase; 11.6% preG1 apoptosis induction and 83.1% in vitro tubulin inhibition (at concentration = IC50). Future researchers in bis-hydrazide tubulin inhibitors are advised to consider the 2-chloro-N-(4-substituted-phenyl)acetamide derivatives as compound 13f due to extra-binding properties of their ring B.