(3R,5S,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(5-methylpyridin-2-yl)propyl)piperidin-2-one | 1619258-07-9

• 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: (3R,5S,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(5-methylpyridin-2-yl)propyl)piperidin-2-one
• CAS: 1619258-07-9
• 化学式: C₃₀H₃₂Cl₂N₂O
• 分子量: 507.503
• InChiKey: BRJZEYWOZXNYRF-QGLFWIBISA-N

物化性质

• 沸点：
  622.2±55.0 °C(predicted)
• 密度：
  1.165±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.49
• 重原子数：
  35.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  33.2
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (3R,5S,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(5-methylpyridin-2-yl)propyl)piperidin-2-one 在 ruthenium trichloride 、 sodium periodate 作用下， 以 四氯化碳 、 水 、 乙腈 为溶剂， 反应 0.75h， 以66%的产率得到2-((3R,5S,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(5-methylpyridin-2-yl)propyl)-2-oxopiperidin-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
• 作为产物：
  描述：

  5-bromo-2-(1-bromopropyl)pyridine 在 potassium phosphate 、 palladium diacetate 、 sodium hydride 、 三环己基膦 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 8.3h， 生成 (3R,5S,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(5-methylpyridin-2-yl)propyl)piperidin-2-one
  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