(2'R,3S,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-piperidin-1-yl-ethyl)-amide

• 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: (2'R,3S,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-piperidin-1-yl-ethyl)-amide
• 英文别名: Spiro-oxindole, 10；(2'R,3S,3'S,5'R)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-2-oxo-N-(2-piperidin-1-ylethyl)spiro[1H-indole-3,4'-pyrrolidine]-2'-carboxamide
• 化学式: C₃₀H₃₇Cl₂FN₄O₂
• 分子量: 575.554
• InChiKey: FFQBAPRTDPSSEL-HVHHDALESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  73.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,3-二甲基丁醛 在 lead(IV) acetate 、 4 A molecular sieve 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 (2'R,3S,4'S,5'R)-6-chloro-4'-(3-chloro-2-fluoro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-piperidin-1-yl-ethyl)-amide
  参考文献：
  名称：

  Structure-Based Design of Spiro-oxindoles as Potent, Specific Small-Molecule Inhibitors of the MDM2−p53 Interaction

  摘要：

  Potent, specific, non-peptide small-molecule inhibitors of the MDM2-p53 interaction were successfully designed. The most potent inhibitor ( MI-63) has a K-i value of 3 nM binding to MDM2 and greater than 10 000-fold selectivity over Bcl-2/Bcl-xL proteins. MI-63 is highly effective in activation of p53 function and in inhibition of cell growth in cancer cells with wild-type p53 status. MI-63 has excellent specificity over cancer cells with deleted p53 and shows a minimal toxicity to normal cells.

  DOI：

  10.1021/jm051122a

文献信息

• SMALL MOLECULE INHIBITORS OF MDM2 AND THE USES THEREOF
  申请人：Wang Shaomeng

  公开号：US20100273799A1

  公开（公告）日：2010-10-28

  The invention relates to small molecules which function as inhibitors of the interaction between p53 and MDM2. The invention also relates to the use of these compounds for inhibiting cell growth, inducing cell death, inducing cell cycle arrest and/or sensitizing cells to additional agent(s).

  本发明涉及作为p53和MDM2之间相互作用抑制剂的小分子。本发明还涉及使用这些化合物来抑制细胞生长，诱导细胞死亡，诱导细胞周期停滞和/或使细胞对其他药物敏感。
• PROCESS FOR THE PREPARATION OF SMALL MOLECULE INHIBITORS OF MDM2 AND INTERMEDIATES USED THEREIN
  申请人：Wang Shaomeng

  公开号：US20130030173A1

  公开（公告）日：2013-01-31

  The invention relates to small molecules which function as inhibitors of the interaction between p53 and MDM2. The invention also relates to the use of these compounds for inhibiting cell growth, inducing cell death, inducing cell cycle arrest and/or sensitizing cells to additional agent(s).

  本发明涉及作为p53和MDM2相互作用抑制剂的小分子。本发明还涉及使用这些化合物来抑制细胞生长，诱导细胞死亡，诱导细胞周期阻滞和/或使细胞对其他药物敏感。
• US7759383B2
  申请人：——

  公开号：US7759383B2

  公开（公告）日：2010-07-20
• US8088931B2
  申请人：——

  公开号：US8088931B2

  公开（公告）日：2012-01-03
• US8742121B2
  申请人：——

  公开号：US8742121B2

  公开（公告）日：2014-06-03