17-benzyl-16-tert-butyl-5-methyl(5S,16S,17R)-18-[4-(benzyloxy)phenyl]-3,11-dioxo-1-phenyl-2,12-dioxa-4,10-diazaoctadecane-5,16,17-tricarboxylate | 377088-78-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 17-benzyl-16-tert-butyl-5-methyl(5S,16S,17R)-18-[4-(benzyloxy)phenyl]-3,11-dioxo-1-phenyl-2,12-dioxa-4,10-diazaoctadecane-5,16,17-tricarboxylate
• 英文别名: 4-O-benzyl 1-O-tert-butyl (2S,3R)-2-[3-[[(5S)-6-methoxy-6-oxo-5-(phenylmethoxycarbonylamino)hexyl]carbamoyloxy]propyl]-3-[(4-phenylmethoxyphenyl)methyl]butanedioate
• CAS: 377088-78-3
• 化学式: C₄₈H₅₈N₂O₁₁
• 分子量: 838.995
• InChiKey: ZTTGNRVSJITBMS-ZMWLRIRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  61
• 可旋转键数：
  29
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  165
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  17-benzyl-16-tert-butyl-5-methyl(5S,16S,17R)-18-[4-(benzyloxy)phenyl]-3,11-dioxo-1-phenyl-2,12-dioxa-4,10-diazaoctadecane-5,16,17-tricarboxylate 在 palladium on activated charcoal 、 四(三苯基膦)钯 lithium hydroxide 、 水 、 氢气 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 tert-butyl(8S,11R,12S)-8-({[2-(4-morpholinyl)-2-oxoethyl]amino}carbonyl)-2,10-dioxo-11-{[2'-(trifluoromethyl)-1,1'-biphenyl-4-yl]methyl}-1-oxa-3,9-diazacyclopentadecane-12-carboxylate
  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 N-甲基吗啉 、 lithium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 正丁基锂 、 双氧水 、 氯化二乙基铝 、 三甲基乙酰氯 、 potassium carbonate 、 二异丙胺 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 17-benzyl-16-tert-butyl-5-methyl(5S,16S,17R)-18-[4-(benzyloxy)phenyl]-3,11-dioxo-1-phenyl-2,12-dioxa-4,10-diazaoctadecane-5,16,17-tricarboxylate
  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.