2-(4-benzylpiperazin-1-yl)-N-(6-methyl-1,3-benzothiazol-2-yl)acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(4-benzylpiperazin-1-yl)-N-(6-methyl-1,3-benzothiazol-2-yl)acetamide
• 化学式: C₂₁H₂₄N₄OS
• mdl: MFCD07469394
• 分子量: 380.514
• InChiKey: FBIFBGFQESJOFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-6-甲基苯并噻唑 在 potassium carbonate 、 三乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 2-(4-benzylpiperazin-1-yl)-N-(6-methyl-1,3-benzothiazol-2-yl)acetamide
  参考文献：
  名称：

  Targeting EGFR tyrosine kinase: Synthesis, in vitro antitumor evaluation, and molecular modeling studies of benzothiazole-based derivatives

  摘要：

  New benzothiazole-based derivatives were synthesized in the present work with the aim of evaluating their antitumor activity. They were in vitro tested against hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116), mammary gland cancer (MCF-7), prostate cancer (PC-3), and epithelioid carcinoma (HeLa). The results of the in vitro antitumor evaluation revealed that the most active compounds were 39, 40, 51, 56, and 61 exhibiting IC50 values comparable to the reference drug lapatinib. The most active compounds were further subjected to EGFR inhibitory activity assay to rationalize their potency mode. Notably, the most active antitumor compounds 39 and 40 represented the most potent inhibitors to EGFR with IC50 values of 24.58 and 30.42 nM respectively in comparison with 17.38 nM for lapatinib as a standard drug. Molecular modeling studies were also conducted for the synthesized compounds, including docking into EGFR active site and surface mapping. Results proved the superior binding of the hydrazone derivatives 39 and 40 with EGFR suggesting them as good candidates for targeted antitumor therapy through EGFR kinase inhibition.

  DOI：

  10.1016/j.bioorg.2020.104259

文献信息

• Targeting EGFR tyrosine kinase: Synthesis, in vitro antitumor evaluation, and molecular modeling studies of benzothiazole-based derivatives
  作者：Amal M. Mokhtar、Shahenda M. El-Messery、Mariam A. Ghaly、Ghada S. Hassan

  DOI：10.1016/j.bioorg.2020.104259

  日期：2020.11

  New benzothiazole-based derivatives were synthesized in the present work with the aim of evaluating their antitumor activity. They were in vitro tested against hepatocellular carcinoma (HepG2), colorectal carcinoma (HCT-116), mammary gland cancer (MCF-7), prostate cancer (PC-3), and epithelioid carcinoma (HeLa). The results of the in vitro antitumor evaluation revealed that the most active compounds were 39, 40, 51, 56, and 61 exhibiting IC50 values comparable to the reference drug lapatinib. The most active compounds were further subjected to EGFR inhibitory activity assay to rationalize their potency mode. Notably, the most active antitumor compounds 39 and 40 represented the most potent inhibitors to EGFR with IC50 values of 24.58 and 30.42 nM respectively in comparison with 17.38 nM for lapatinib as a standard drug. Molecular modeling studies were also conducted for the synthesized compounds, including docking into EGFR active site and surface mapping. Results proved the superior binding of the hydrazone derivatives 39 and 40 with EGFR suggesting them as good candidates for targeted antitumor therapy through EGFR kinase inhibition.