2-chloro-N-(4-(2-(3,4,5-trimethoxybenzoyl)hydrazinecarbonyl)phenyl)acetamide

• 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: 2-chloro-N-(4-(2-(3,4,5-trimethoxybenzoyl)hydrazinecarbonyl)phenyl)acetamide
• 英文别名: 2-chloro-N-[4-[[(3,4,5-trimethoxybenzoyl)amino]carbamoyl]phenyl]acetamide
• 化学式: C₁₉H₂₀ClN₃O₆
• 分子量: 421.837
• InChiKey: OGUCMMHPIUAGCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.96
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  114.99
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4-(2-(3,4,5-trimethoxybenzoyl)hydrazinecarbonyl)phenyl)acetamide 在 sodium azide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以44%的产率得到2-azido-N-(4-(2-(3,4,5-trimethoxybenzoyl)hydrazinecarbonyl) phenyl) acetamide
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bioorg.2020.103767
• 作为产物：
  描述：

  没食子酸 在 一水合肼 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 2-chloro-N-(4-(2-(3,4,5-trimethoxybenzoyl)hydrazinecarbonyl)phenyl)acetamide
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bioorg.2020.103767

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.