12-tert-butyl-8-methyl(8S,11R,12S)-2,10-dioxo-11{[2'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methyl}-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate | 377088-80-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 12-tert-butyl-8-methyl(8S,11R,12S)-2,10-dioxo-11{[2'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methyl}-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate
• 英文别名: 12-O-tert-butyl 8-O-methyl (8S,11R,12S)-2,10-dioxo-11-[[4-[2-(trifluoromethyl)phenyl]phenyl]methyl]-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate
• CAS: 377088-80-7
• 化学式: C₃₃H₄₁F₃N₂O₇
• 分子量: 634.693
• InChiKey: MTQIXESJCZLZOD-WEWMWRJBSA-N

物化性质

• 沸点：
  772.4±60.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  45
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  12-tert-butyl-8-methyl(8S,11R,12S)-2,10-dioxo-11{[2'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methyl}-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate 在 lithium hydroxide 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以100%的产率得到
  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 palladium on activated charcoal 、 四(三苯基膦)钯 N-甲基吗啉 、 lithium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 正丁基锂 、 氢气 、 双氧水 、 氯化二乙基铝 、 三甲基乙酰氯 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 二异丙胺 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 12-tert-butyl-8-methyl(8S,11R,12S)-2,10-dioxo-11{[2'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methyl}-1-oxa-3,9-diazacyclopentadecane-8,12-dicarboxylate
  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.