(Z)-2-((4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino)-5-((E)-3-(4-methoxyphenyl)allylidene)thiazol-4(5H)-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (Z)-2-((4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino)-5-((E)-3-(4-methoxyphenyl)allylidene)thiazol-4(5H)-one
• 英文别名: (2E,5Z)-2-[(4-acetyl-5-methyl-5-phenyl-1,3,4-thiadiazol-2-yl)imino]-5-[(E)-3-(4-methoxyphenyl)prop-2-enylidene]-1,3-thiazolidin-4-one
• 化学式: C₂₄H₂₂N₄O₃S₂
• 分子量: 478.596
• InChiKey: GGPRILSFJGQRPO-SKRUYSPESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(5-amino-2-methyl-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-ethan-1-one 在 硫氰酸铵 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (Z)-2-((4-acetyl-5-methyl-5-phenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl)amino)-5-((E)-3-(4-methoxyphenyl)allylidene)thiazol-4(5H)-one
  参考文献：
  名称：

  Design and synthesis of novel thiadiazole-thiazolone hybrids as potential inhibitors of the human mitotic kinesin Eg5

  摘要：

  A novel series of 1,3,4-thiadiazole-thiazolone hybrids 5a-v were designed, synthesized, characterized, and evaluated against the basal and the microtubule (MT)-stimulated ATPase activity of Eg5. From the evaluated derivatives, 5h displayed the highest inhibition with an IC50 value of 13.2 mu M against the MT-stimulated Eg5 ATPase activity. Similarly, compounds 5f and 5i also presented encouraging inhibition with IC50 of 17.2 mu M and 20.2 mu M, respectively. A brief structure-activity relationship (SAR) analysis indicated that 2-chloro and 4-nitro substituents on the phenyl ring of the thiazolone motif contributed significantly to enzyme inhibition. An in silico molecular docking study using the crystal structure of Eg5 further supported the SAR and reasoned the importance of crucial molecular protein-ligand interactions in influencing the inhibition of the ATPase activity of Eg5. The magnitude of the electron-withdrawing functionalities over the hybrids and the critical molecular interactions contributed towards higher in vitro potency of the compounds. The drug-like properties of the synthesized compounds 5a-v were also calculated based on the Lipinski's rule of five and in silico computation of key pharmacokinetic parameters (ADME). Thus, the present work unveils these hybrid molecules as novel Eg5 inhibitors with promising drug-like properties for future development.

  DOI：

  10.1016/j.bmcl.2018.07.007