(2'R,3'S,4'R,5'R)-6-Chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-1'-((1R,2S)-2-hydroxy-1,2-diphenyl-ethyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-morpholin-4-yl-ethyl)-amide | 897365-78-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (2'R,3'S,4'R,5'R)-6-Chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-1'-((1R,2S)-2-hydroxy-1,2-diphenyl-ethyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-morpholin-4-yl-ethyl)-amide
• 英文别名: (2a(2)R,3S,4a(2)R,5a(2)R)-6-Chloro-4a(2)-(3-chlorophenyl)-2a(2)-(2,2-dimethylpropyl)-1,2-dihydro-1a(2)-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-N-[2-(4-morpholinyl)ethyl]-2-oxospiro[3H-indole-3,3a(2)-pyrrolidine]-5a(2)-carboxamide；(2'R,3S,3'R,5'R)-6-chloro-3'-(3-chlorophenyl)-5'-(2,2-dimethylpropyl)-1'-[(1R,2S)-2-hydroxy-1,2-diphenylethyl]-N-(2-morpholin-4-ylethyl)-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carboxamide
• CAS: 897365-78-5
• 化学式: C₄₃H₄₈Cl₂N₄O₄
• 分子量: 755.785
• InChiKey: BCGWPLVKHBMGOP-IIRGSQAISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.38
• 重原子数：
  53.0
• 可旋转键数：
  10.0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  94.14
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2'R,3'S,4'R,5'R)-6-Chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-1'-((1R,2S)-2-hydroxy-1,2-diphenyl-ethyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-morpholin-4-yl-ethyl)-amide 在 lead(IV) acetate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (2'R,3S,4'R,5'R)-6-chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-morpholin-4-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
• 作为产物：
  描述：

  6-chloro-3-[1-(3-chloro-phenyl)-meth-(E)-ylidene]-1,3-dihydro-indol-2-one 在 4 A molecular sieve 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 (2'R,3'S,4'R,5'R)-6-Chloro-4'-(3-chloro-phenyl)-2'-(2,2-dimethyl-propyl)-1'-((1R,2S)-2-hydroxy-1,2-diphenyl-ethyl)-2-oxo-1,2-dihydro-spiro[indole-3,3'-pyrrolidine]-5'-carboxylic acid (2-morpholin-4-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