4-benzyl-1-tert-butyl(2S,3R)-2-allyl-3-[4-(benzyloxy)benzyl]butanedioate | 377088-76-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-benzyl-1-tert-butyl(2S,3R)-2-allyl-3-[4-(benzyloxy)benzyl]butanedioate
• 英文别名: 4-O-benzyl 1-O-tert-butyl (2S,3R)-3-[(4-phenylmethoxyphenyl)methyl]-2-prop-2-enylbutanedioate
• CAS: 377088-76-1
• 化学式: C₃₂H₃₆O₅
• 分子量: 500.635
• InChiKey: AYKKDBKPXWHTLV-URLMMPGGSA-N

物化性质

• 沸点：
  605.4±55.0 °C(Predicted)
• 密度：
  1.107±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-benzyl-1-tert-butyl(2S,3R)-2-allyl-3-[4-(benzyloxy)benzyl]butanedioate 在 palladium on activated charcoal 、 四(三苯基膦)钯 N-甲基吗啉 、 lithium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 盐酸羟胺 、 水 、 氢气 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2,10-Dioxo-11-(2''-trifluoromethyl-biphenyl-4-ylmethyl)-1-oxa-3,9-diaza-cyclopentadecane-8,12-dicarboxylic acid 12-hydroxyamide 8-[(2-oxo-2-piperazin-1-yl-ethyl)-amide]
  参考文献：
  名称：

  Discovery of Macrocyclic Hydroxamic Acids Containing Biphenylmethyl Derivatives at P1‘, a Series of Selective TNF-α Converting Enzyme Inhibitors with Potent Cellular Activity in the Inhibition of TNF-α Release

  摘要：

  SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrate for the first time that TACE has a larger S1' pocket in comparison to MMPs and that potent and selective TACE inhibitors can be achieved by incorporation of sterically bulky P1' residues.

  DOI：

  10.1021/jm0155502
• 作为产物：
  描述：

  3-[4-(苄氧基)苯基]丙酸 在 lithium hydroxide 、 正丁基锂 、 双氧水 、 氯化二乙基铝 、 三甲基乙酰氯 、 二异丙胺 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 6.0h， 生成 4-benzyl-1-tert-butyl(2S,3R)-2-allyl-3-[4-(benzyloxy)benzyl]butanedioate
  参考文献：
  名称：

  Discovery of Macrocyclic Hydroxamic Acids Containing Biphenylmethyl Derivatives at P1‘, a Series of Selective TNF-α Converting Enzyme Inhibitors with Potent Cellular Activity in the Inhibition of TNF-α Release

  摘要：

  SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrate for the first time that TACE has a larger S1' pocket in comparison to MMPs and that potent and selective TACE inhibitors can be achieved by incorporation of sterically bulky P1' residues.

  DOI：

  10.1021/jm0155502

文献信息

• Discovery of Macrocyclic Hydroxamic Acids Containing Biphenylmethyl Derivatives at P1‘, a Series of Selective TNF-α Converting Enzyme Inhibitors with Potent Cellular Activity in the Inhibition of TNF-α Release
  作者：Chu-Biao Xue、Xiaohua He、Ronald L. Corbett、John Roderick、Zelda R. Wasserman、Rui-Qin Liu、Bruce D. Jaffee、Maryanne B. Covington、Mingxin Qian、James M. Trzaskos、Robert C. Newton、Ronald L. Magolda、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm0155502

  日期：2001.10.1

  SAR exploration at P1' using an anti-succinate-based macrocyclic hydroxamic acid as a template led to the identification of several bulky biphenylmethyl P1' derivatives which confer potent porcine TACE and anti-TNF-alpha cellular activities with high selectivity versus most of the MMPs screened. Our studies demonstrate for the first time that TACE has a larger S1' pocket in comparison to MMPs and that potent and selective TACE inhibitors can be achieved by incorporation of sterically bulky P1' residues.