methyl 4-[(tert-butyldiphenylsilyl)oxy]-3-hydroxybutanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: methyl 4-[(tert-butyldiphenylsilyl)oxy]-3-hydroxybutanoate
• 英文别名: Methyl 4-[tert-butyl(diphenyl)silyl]oxy-3-hydroxybutanoate
• 化学式: C₂₁H₂₈O₄Si
• 分子量: 372.536
• InChiKey: IYARNAWKJBPAJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.49
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-[(tert-butyldiphenylsilyl)oxy]-3-hydroxybutanoate 在 草酰氯 、 1,8-双二甲氨基萘 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 34.92h， 生成 tert-butyl N-[2-({5-[(4-{3-[(tert-butyldiphenylsilyl)oxy]-2-methoxypropyl}-1,3-thiazol-2-yl)amino]-2,2'-dimethyl[1,1'-biphenyl]-4-yl}oxy)ethyl]carbamate
  参考文献：
  名称：

  Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA₂) Discovered through X-ray Fragment Screening

  摘要：

  Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA(2) in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 A from the catalytic residue Ser273). Using structure guided design, we optimized a fragment that bound in this pocket to generate a novel low nanomolar chemotype, which did not interact with the catalytic residues.

  DOI：

  10.1021/acs.jmedchem.6b00212
• 作为产物：
  描述：

  3-丁烯酸甲酯 在 4-二甲氨基吡啶 、 四氧化锇 、 N-甲基吗啉氧化物 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 64.17h， 生成 methyl 4-[(tert-butyldiphenylsilyl)oxy]-3-hydroxybutanoate
  参考文献：
  名称：

  Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA₂) Discovered through X-ray Fragment Screening

  摘要：

  Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA(2)) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA(2) in order to identify novel inhibitors. Multiple fragment hits were observed in different regions of the active site, including some hits that bound in a pocket created by movement of a protein side chain (approximately 13 A from the catalytic residue Ser273). Using structure guided design, we optimized a fragment that bound in this pocket to generate a novel low nanomolar chemotype, which did not interact with the catalytic residues.

  DOI：

  10.1021/acs.jmedchem.6b00212