(S,Z)-2-(5-(4-(4-chloro-3,5-dimethylphenoxy)benzylidene)-2,4-dioxothiazolidin-3-yl)-4-methyl pentanoic acid

• 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: (S,Z)-2-(5-(4-(4-chloro-3,5-dimethylphenoxy)benzylidene)-2,4-dioxothiazolidin-3-yl)-4-methyl pentanoic acid
• 英文别名: (2S)-2-[(5Z)-5-[[4-(4-chloro-3,5-dimethylphenoxy)phenyl]methylidene]-2,4-dioxo-1,3-thiazolidin-3-yl]-4-methylpentanoic acid
• 化学式: C₂₄H₂₄ClNO₅S
• 分子量: 473.977
• InChiKey: IAAARCIENVFTHV-SCWSXOCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S,Z)-2-(5-(4-(4-chloro-3,5-dimethylphenoxy)benzylidene)-2,4-dioxothiazolidin-3-yl)-4-methyl pentanoic acid 在 氯化铵 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以50%的产率得到(S,Z)-2-(5-(4-(4-chloro-3,5-dimethylphenoxy)benzylidene)-2,4-dioxothiazolidin-3-yl)-4-methyl pentanamide
  参考文献：
  名称：

  Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold

  摘要：

  Inspired by a rhodanine-based dual inhibitor of Bcl-x(L) and Mcl-1, a focused library of analogues was prepared wherein the rhodanine core was replaced with a less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b inhibited Mcl-1 with a K-i of 155 nM. Further investigation revealed comparable inhibition of Bcl-x(L) (K-i = 90 nM), indicating that the dual inhibitory profile of the initial rhodanine lead had been retained upon switching the heterocycle core. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.023
• 作为产物：
  描述：

  4-氯-3,5-二甲基苯酚 在 哌啶 、 硫酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 (S,Z)-2-(5-(4-(4-chloro-3,5-dimethylphenoxy)benzylidene)-2,4-dioxothiazolidin-3-yl)-4-methyl pentanoic acid
  参考文献：
  名称：

  Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold

  摘要：

  Inspired by a rhodanine-based dual inhibitor of Bcl-x(L) and Mcl-1, a focused library of analogues was prepared wherein the rhodanine core was replaced with a less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b inhibited Mcl-1 with a K-i of 155 nM. Further investigation revealed comparable inhibition of Bcl-x(L) (K-i = 90 nM), indicating that the dual inhibitory profile of the initial rhodanine lead had been retained upon switching the heterocycle core. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.023