2-((3R,5R,6S)-5-(3-chlorophenyl)-6-( 4-chlorophenyl)-3-methyl-2-oxo-l-( (1 S)-1(tetrahydrofuran-2-yl)propyl)piperidin-3-yl)acetic acid | 1352065-43-0

• 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-((3R,5R,6S)-5-(3-chlorophenyl)-6-( 4-chlorophenyl)-3-methyl-2-oxo-l-( (1 S)-1(tetrahydrofuran-2-yl)propyl)piperidin-3-yl)acetic acid
• 英文别名: 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((1S)-1-(tetrahydrofuran-2-yl)propyl)piperidin-3-yl)acetic acid；2-((3R,5R,6S)-5-(3-Chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-((S)-tetrahydrofuran-2-yl)propyl)piperidin-3-yl)acetic acid；2-[(3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-[(1S)-1-[(2S)-oxolan-2-yl]propyl]piperidin-3-yl]acetic acid
• CAS: 1352065-43-0
• 化学式: C₂₇H₃₁Cl₂NO₄
• 分子量: 504.453
• InChiKey: WWKWPSAIEAMHPQ-DZHCERKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal 在 ruthenium trichloride 、 sodium periodate 、 二乙基偶氮二羧酸酯 、 四丁基氟化铵 、 三苯基膦 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 6.25h， 生成 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-( 4-chlorophenyl)-3-methyl-2-oxo-l-( (1 S)-1(tetrahydrofuran-2-yl)propyl)piperidin-3-yl)acetic acid
  参考文献：
  名称：

  Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2–p53 Interaction

  摘要：

  Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone-pyridine inhibitors 6, 7, 14, and 15 with improved pharmacokinetic properties in rats. Reducing structure complexity of the N-alkyl substituent led to the discovery of 23, a potent and simplified inhibitor of MDM2. Compound 23 exhibits excellent pharmacokinetic properties and substantial in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft mouse model.

  DOI：

  10.1021/ml500142b

文献信息

• Discovery of Potent and Simplified Piperidinone-Based Inhibitors of the MDM2–p53 Interaction
  作者：Ming Yu、Yingcai Wang、Jiang Zhu、Michael D. Bartberger、Jude Canon、Ada Chen、David Chow、John Eksterowicz、Brian Fox、Jiasheng Fu、Michael Gribble、Xin Huang、Zhihong Li、Jiwen (Jim) Liu、Mei-chu Lo、Dustin McMinn、Jonathan D. Oliner、Tao Osgood、Yosup Rew、Anne Y. Saiki、Paul Shaffer、Xuelei Yan、Qiuping Ye、Dongyin Yu、Xiaoning Zhao、Jing Zhou、Steven H. Olson、Julio C. Medina、Daqing Sun

  DOI：10.1021/ml500142b

  日期：2014.8.14

  Continued optimization of the N-substituent in the piperidinone series provided potent piperidinone-pyridine inhibitors 6, 7, 14, and 15 with improved pharmacokinetic properties in rats. Reducing structure complexity of the N-alkyl substituent led to the discovery of 23, a potent and simplified inhibitor of MDM2. Compound 23 exhibits excellent pharmacokinetic properties and substantial in vivo antitumor activity in the SJSA-1 osteosarcoma xenograft mouse model.