2-phthalimido-N-<2-<(tert-butyldimethylsiloxy)oxy>-3,3,3-trifluoro-1-isopropyl>acetamide | 159780-13-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-phthalimido-N-<2-<(tert-butyldimethylsiloxy)oxy>-3,3,3-trifluoro-1-isopropyl>acetamide
• 英文别名: N-(2-tert-Butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropyl-propyl)-2-phthalimidoacetamide；N-[2-[tert-butyl(dimethyl)silyl]oxy-1,1,1-trifluoro-4-methylpentan-3-yl]-2-(1,3-dioxoisoindol-2-yl)acetamide
• CAS: 159780-13-9
• 化学式: C₂₂H₃₁F₃N₂O₄Si
• 分子量: 472.58
• InChiKey: RLHMIZVGIHWFPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.38
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-phthalimido-N-<2-<(tert-butyldimethylsiloxy)oxy>-3,3,3-trifluoro-1-isopropyl>acetamide 在 lithium hydroxide 、 TEA 、 叠氮磷酸二苯酯 、 一水合肼 、 lithium iodide 作用下， 以 1,4-二氧六环 、 吡啶 、 乙醇 为溶剂， 120.0 ℃ 、133.32 Pa 条件下， 反应 54.0h， 生成 2-(3-Benzyloxycarbonylamino-4-carboxy-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(2-tert-butyldimethylsilyloxy-3,3,3-trifluoro-1-isopropylpropyl)acetamide
  参考文献：
  名称：

  Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones

  摘要：

  Using molecular modeling and the information derived from X-ray crystal structures of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) complexed to peptidic ligands, we have developed a new series of nonpeptidic inhibitors of HNE, the pyridopyrimidine trifluoromethyl ketones (TFMKs). These bicyclic inhibitors were designed to extend the concept of the related pyridone trifluoromethyl ketones by incorporating a rigidly positioned carbonyl group to participate in a hydrogen bonding interaction with the backbone NH groups of Gly-218 and Gly-219 of the enzyme. In addition, the pyrimidine ring serves as a scaffold to vector substituents toward the S-5-S-4 subsites of the enzyme's extended binding pocket. Furthermore, the heteroatoms of the pyrimidine ring generally increase the aqueous solubility of the pyridopyrimidines relative to pyridone TFMKs. Pyridopyrimidine TFMKs containing a 6-phenyl substituent afforded potent inhibitors of elastase, and several inhibitors from this class of compounds possessed aqueous solubilities of > 0.1 mg/mL and K-i values of less than or equal to 10 nM.

  DOI：

  10.1021/jm950684z
• 作为产物：
  描述：

  邻苯二甲酰甘氨酸 在 N-甲基吗啉 、 2,6-二甲基吡啶 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 生成 2-phthalimido-N-<2-<(tert-butyldimethylsiloxy)oxy>-3,3,3-trifluoro-1-isopropyl>acetamide
  参考文献：
  名称：

  Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and in Vitro Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones

  摘要：

  Using molecular modeling and the information derived from X-ray crystal structures of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) complexed to peptidic ligands, we have developed a new series of nonpeptidic inhibitors of HNE, the pyridopyrimidine trifluoromethyl ketones (TFMKs). These bicyclic inhibitors were designed to extend the concept of the related pyridone trifluoromethyl ketones by incorporating a rigidly positioned carbonyl group to participate in a hydrogen bonding interaction with the backbone NH groups of Gly-218 and Gly-219 of the enzyme. In addition, the pyrimidine ring serves as a scaffold to vector substituents toward the S-5-S-4 subsites of the enzyme's extended binding pocket. Furthermore, the heteroatoms of the pyrimidine ring generally increase the aqueous solubility of the pyridopyrimidines relative to pyridone TFMKs. Pyridopyrimidine TFMKs containing a 6-phenyl substituent afforded potent inhibitors of elastase, and several inhibitors from this class of compounds possessed aqueous solubilities of > 0.1 mg/mL and K-i values of less than or equal to 10 nM.

  DOI：

  10.1021/jm950684z

文献信息

• Nonpeptidic Inhibitors of Human Neutrophil Elastase. 7. Design, Synthesis, and <i>in Vitro</i> Activity of a Series of Pyridopyrimidine Trifluoromethyl Ketones
  作者：Philip D. Edwards、Donald W. Andisik、Anne M. Strimpler、Bruce Gomes、Paul A. Tuthill

  DOI：10.1021/jm950684z

  日期：1996.1.1

  Using molecular modeling and the information derived from X-ray crystal structures of human neutrophil elastase (HNE) and porcine pancreatic elastase (PPE) complexed to peptidic ligands, we have developed a new series of nonpeptidic inhibitors of HNE, the pyridopyrimidine trifluoromethyl ketones (TFMKs). These bicyclic inhibitors were designed to extend the concept of the related pyridone trifluoromethyl ketones by incorporating a rigidly positioned carbonyl group to participate in a hydrogen bonding interaction with the backbone NH groups of Gly-218 and Gly-219 of the enzyme. In addition, the pyrimidine ring serves as a scaffold to vector substituents toward the S-5-S-4 subsites of the enzyme's extended binding pocket. Furthermore, the heteroatoms of the pyrimidine ring generally increase the aqueous solubility of the pyridopyrimidines relative to pyridone TFMKs. Pyridopyrimidine TFMKs containing a 6-phenyl substituent afforded potent inhibitors of elastase, and several inhibitors from this class of compounds possessed aqueous solubilities of > 0.1 mg/mL and K-i values of less than or equal to 10 nM.