(1R,2S)-1,2-双(4-氯苯基)丙烷-1,2-二胺L-酒石酸盐 | 1033712-88-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 中文名称: (1R,2S)-1,2-双(4-氯苯基)丙烷-1,2-二胺L-酒石酸盐
• 英文名称: (1R,2S)-1,2-bis(4-chlorophenyl)propane-1,2-diamine L-tartrate
• CAS: 1033712-88-7
• 化学式: C₄H₆O₆*C₁₅H₁₆Cl₂N₂
• 分子量: 445.299
• InChiKey: XEZQODNXUOHAHV-YFHUMEBCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.74
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  167.1
• 氢给体数：
  6.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (1R,2S)-1,2-双(4-氯苯基)丙烷-1,2-二胺L-酒石酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-{[(5R,6S)-5,6-Bis(4-chlorophenyl)-3-isopropyl-6-methyl-5,6-dihydroimidazo[2,1-b][1,3]thiazol-2-yl]carbonyl}-L-proline
  参考文献：
  名称：

  Lead optimization of novel p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold

  摘要：

  With the aim of discovering potent inhibitors of the p53-MDM2 interaction and thus obtaining a potent anticancer drug, we have pursued synthesis and optimization of dihydroimidazothiazole derivatives, which have been discovered via scaffold hopping by mimicing the mode of interaction between MDM2 and Nutlins. Upon the discovery we encountered a problem involving the chemical instability of the scaffold, that is, susceptibility to oxidation which led to imidazothiazole. In order to solve this problem and to obtain further potent compounds, we executed medicinal research and thus furnished the optimal compounds by incorporating the methyl group onto the C-6 position to avoid the oxidation, and by modifying the C-2 moiety of the additional proline motif, which furnished high potency. The incorporation of the pyrrolidine moiety at the C-2 position raised another hydrophobic interaction site with MDM2 protein, which was generated by the induced-fitting observed by co-crystal structure analysis. These optimal molecules showed significant improvement in potency when compared with the early lead (+)-1 or Nutlin-3a. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.091
• 作为产物：
  描述：

  (1R*,2S*)-1,2-bis(4-chlorophenyl)propane-1,2-diamine 、 L-酒石酸 以 乙醇 为溶剂， 生成 (1R,2S)-1,2-双(4-氯苯基)丙烷-1,2-二胺L-酒石酸盐 、 1,2-bis(4-chlorophenyl)propane-1,2-diamine L-tartrate
  参考文献：
  名称：

  Lead optimization of novel p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold

  摘要：

  With the aim of discovering potent inhibitors of the p53-MDM2 interaction and thus obtaining a potent anticancer drug, we have pursued synthesis and optimization of dihydroimidazothiazole derivatives, which have been discovered via scaffold hopping by mimicing the mode of interaction between MDM2 and Nutlins. Upon the discovery we encountered a problem involving the chemical instability of the scaffold, that is, susceptibility to oxidation which led to imidazothiazole. In order to solve this problem and to obtain further potent compounds, we executed medicinal research and thus furnished the optimal compounds by incorporating the methyl group onto the C-6 position to avoid the oxidation, and by modifying the C-2 moiety of the additional proline motif, which furnished high potency. The incorporation of the pyrrolidine moiety at the C-2 position raised another hydrophobic interaction site with MDM2 protein, which was generated by the induced-fitting observed by co-crystal structure analysis. These optimal molecules showed significant improvement in potency when compared with the early lead (+)-1 or Nutlin-3a. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.091