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

文献信息

• Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA₂) Discovered through X-ray Fragment Screening
  作者：Alison J.-A. Woolford、Joseph E. Pero、Sridhar Aravapalli、Valerio Berdini、Joseph E. Coyle、Philip J. Day、Andrew M. Dodson、Pascal Grondin、Finn P. Holding、Lydia Y. W. Lee、Peng Li、Eric S. Manas、Joseph Marino、Agnes C. L. Martin、Brent W. McCleland、Rachel L. McMenamin、Christopher W. Murray、Christopher E. Neipp、Lee W. Page、Vipulkumar K. Patel、Florent Potvain、Sharna Rich、Ralph A. Rivero、Kirsten Smith、Donald O. Somers、Lionel Trottet、Ranganadh Velagaleti、Glyn Williams、Ren Xie

  DOI：10.1021/acs.jmedchem.6b00212

  日期：2016.6.9

  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.