1-[6-(4-Chloro-phenoxy)-hexyl]-3-pyrimidin-4-yl-imidazolidin-2-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-[6-(4-Chloro-phenoxy)-hexyl]-3-pyrimidin-4-yl-imidazolidin-2-one
• 英文别名: 1-[6-(4-Chlorophenoxy)hexyl]-3-pyrimidin-4-yl-imidazolidin-2-one；1-[6-(4-chlorophenoxy)hexyl]-3-pyrimidin-4-ylimidazolidin-2-one
• 化学式: C₁₉H₂₃ClN₄O₂
• 分子量: 374.87
• InChiKey: AKKCVXLLGAGCDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(2-Chloro-ethyl)-3-pyrimidin-4-yl-urea 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 1-[6-(4-Chloro-phenoxy)-hexyl]-3-pyrimidin-4-yl-imidazolidin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationship of Pyridyl Imidazolidinones:  A Novel Class of Potent and Selective Human Enterovirus 71 Inhibitors

  摘要：

  When skeletons of Win compounds were used as templates, computer-assisted drug design led to the identification of a novel series of imidazolidinone derivatives with significant antiviral activity against enterovirus 71(EV 71), the infection of which had resulted in about 80 fatalities during the 1998 epidemic outbreak in Taiwan. In addition to inhibiting all the genotypes (A, B, and C) of EV 71 in the submicromolar to low micromolar range, compounds 1 and 8 were extensively evaluated against a variety of viruses, showing potent activity against coxsackievirus A9 (IC50 = 0.47-0.55 muM) and coxsackievirus A24 (IC50 = 0.47-0.55 muM) as well as moderate activity against enterovirus 68 (IC50 = 2.13 muM) and echovirus 9 (IC50 = 2.6 muM). Our SAR studies revealed that imidazolidinone analogues with an aryl substituent at the para position of the phenoxyl ring, such as compounds 20, 21, 27, 57, 58, and 61, in general exhibited the highest activity against EV 71. Among them, compound 20 and its corresponding hydrochloride salt 57, in terms of potency and selectivity index, appear to be the most promising candidates in this series for further development of anti-EV-71 agents. Preliminary results of the study on the mode of action by a time-course experiment suggest that test compounds 1 and 8 can effectively inhibit the virus replication at the early stages, referring to virus attachment or uncoating. This indicates that the surface protein may be the target for this type of compounds.

  DOI：

  10.1021/jm010536a