[(3S,5R)-3-[4-(2-methoxyphenyl)piperazine-1-carbonyl]-5-phenyl-3-[4-(trifluoromethyl)phenoxy]piperidin-1-yl]-[4-(trifluoromethyl)pyridin-3-yl]methanone | 1601475-78-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: [(3S,5R)-3-[4-(2-methoxyphenyl)piperazine-1-carbonyl]-5-phenyl-3-[4-(trifluoromethyl)phenoxy]piperidin-1-yl]-[4-(trifluoromethyl)pyridin-3-yl]methanone
• CAS: 1601475-78-8
• 化学式: C₃₇H₃₄F₆N₄O₄
• 分子量: 712.692
• InChiKey: LSPICVFNSJPUEE-CYFIQEHSSA-N

物化性质

• 沸点：
  806.994±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.342±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  51
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  75.2
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  tert-butyl (R)-3-oxo-5-phenylpiperidine-1-carboxylate 在 盐酸 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 为溶剂， 生成 [(3S,5R)-3-[4-(2-methoxyphenyl)piperazine-1-carbonyl]-5-phenyl-3-[4-(trifluoromethyl)phenoxy]piperidin-1-yl]-[4-(trifluoromethyl)pyridin-3-yl]methanone
  参考文献：
  名称：

  Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction

  摘要：

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.02.055

文献信息

• Core modification of substituted piperidines as Novel inhibitors of HDM2–p53 protein–protein interaction
  作者：Weidong Pan、Brian R. Lahue、Yao Ma、Latha G. Nair、Gerald W. Shipps、Yaolin Wang、Ronald Doll、Stéphane L. Bogen

  DOI：10.1016/j.bmcl.2014.02.055

  日期：2014.4

  The discovery of 3,3-disubstituted piperidine 1 as novel p53-HDM2 inhibitors prompted us to implement subsequent SAR follow up directed towards piperidine core modifications. Conformational restrictions and further functionalization of the piperidine core were investigated as a strategy to gain additional interactions with HDM2. Substitutions at positions 4, 5 and 6 of the piperidine ring were explored. Although some substitutions were tolerated, no significant improvement in potency was observed compared to 1. Incorporation of an allyl side chain at position 2 provided a drastic improvement in binding potency. (C) 2014 Elsevier Ltd. All rights reserved.