1-(2-{(4-chlorobenzyl)-[2-(4'-chlorobiphenyl-4-yloxy)ethyl]amino}ethyl)-3-pyridin-4-ylimidazolidin-2-one

• 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: 1-(2-{(4-chlorobenzyl)-[2-(4'-chlorobiphenyl-4-yloxy)ethyl]amino}ethyl)-3-pyridin-4-ylimidazolidin-2-one
• 英文别名: 1-[2-[(4-Chlorophenyl)methyl-[2-[4-(4-chlorophenyl)phenoxy]ethyl]amino]ethyl]-3-(4-pyridyl)imidazolidin-2-one；1-[2-[(4-chlorophenyl)methyl-[2-[4-(4-chlorophenyl)phenoxy]ethyl]amino]ethyl]-3-pyridin-4-ylimidazolidin-2-one
• 化学式: C₃₁H₃₀Cl₂N₄O₂
• 分子量: 561.511
• InChiKey: BPOYHJWKBMNMQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  48.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯-N-(2-氯乙基)-N-[(4-氯苯基)甲基]乙胺 在 氢氧化钾 、 sodium hydride 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 1-(2-{(4-chlorobenzyl)-[2-(4'-chlorobiphenyl-4-yloxy)ethyl]amino}ethyl)-3-pyridin-4-ylimidazolidin-2-one
  参考文献：
  名称：

  Design, Synthesis, and Antipicornavirus Activity of 1-[5-(4-Arylphenoxy)alkyl]-3-pyridin-4-ylimidazolidin-2-one Derivatives

  摘要：

  A series of pyridylimidazolidinone derivatives was synthesized and tested in vitro against enterovirus 71 (EV71). On the basis of compound 33 (DBPR103), introduction of a methyl group at the 2- or 3-position of the linker between the imidazolidinone and the biphenyl resulted in markedly improved antiviral activity toward EV71 with IC50 values of 5.0 nM (24b) and 9.3 nM (14a), respectively. Increasing the branched chain to propyl resulted in a progressive decrease in activity, while inserting different heteroatoms entirely rendered the compound only weakly active. The introduction of a bulky group (cyclohexyl, phenyl, or benzyl) led to loss of activity against EV71. The 4-chlorophenyl moiety in 14a was replaced with bioisosteric groups such as oxadiazole (28a-d) or tetrazole (32a,b), dramatically improving anti-EV71 activity and selectivity indices. Compounds 14a, 24b, 28b, 28d, and 32a exhibited a strong activity against lethal EV71, and no apparent cellular toxicity was observed. Three of the more potent imidazolidinone compounds, 14a, 28b, and 32b, were subjected to a large group of picornaviruses to determine their spectrum of antiviral activity.

  DOI：

  10.1021/jm050033v

文献信息

• Imidazolidinone compounds
  申请人：——

  公开号：US20040116476A1

  公开（公告）日：2004-06-17

  This invention relates to compounds of the following formula: 1 in which R 1 , R 2 , A 1 , A 2 , X, Y, m, n, p, x and y are as defined herein, pharmaceutical compositions comprising the compounds and use of the compounds in treating enterovirus infection.

  本发明涉及以下式子的化合物：1其中R1，R2，A1，A2，X，Y，m，n，p，x和y如此定义，以及包含这些化合物的药物组成物和使用这些化合物治疗肠道病毒感染。
• US7129359B2
  申请人：——

  公开号：US7129359B2

  公开（公告）日：2006-10-31
• US7501445B2
  申请人：——

  公开号：US7501445B2

  公开（公告）日：2009-03-10
• Design, Synthesis, and Antipicornavirus Activity of 1-[5-(4-Arylphenoxy)alkyl]-3-pyridin-4-ylimidazolidin-2-one Derivatives
  作者：Chih-Shiang Chang、Ying-Ting Lin、Shin-Ru Shih、Chung-Chi Lee、Yen-Chun Lee、Chia-Liang Tai、Sung-Nien Tseng、Jyh-Haur Chern

  DOI：10.1021/jm050033v

  日期：2005.5.1

  A series of pyridylimidazolidinone derivatives was synthesized and tested in vitro against enterovirus 71 (EV71). On the basis of compound 33 (DBPR103), introduction of a methyl group at the 2- or 3-position of the linker between the imidazolidinone and the biphenyl resulted in markedly improved antiviral activity toward EV71 with IC50 values of 5.0 nM (24b) and 9.3 nM (14a), respectively. Increasing the branched chain to propyl resulted in a progressive decrease in activity, while inserting different heteroatoms entirely rendered the compound only weakly active. The introduction of a bulky group (cyclohexyl, phenyl, or benzyl) led to loss of activity against EV71. The 4-chlorophenyl moiety in 14a was replaced with bioisosteric groups such as oxadiazole (28a-d) or tetrazole (32a,b), dramatically improving anti-EV71 activity and selectivity indices. Compounds 14a, 24b, 28b, 28d, and 32a exhibited a strong activity against lethal EV71, and no apparent cellular toxicity was observed. Three of the more potent imidazolidinone compounds, 14a, 28b, and 32b, were subjected to a large group of picornaviruses to determine their spectrum of antiviral activity.