(1R*,2S*,3R*,4S*,5S*)-2-benzyloxycarbonylamino-6-formylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R*,2S*,3R*,4S*,5S*)-2-benzyloxycarbonylamino-6-formylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester
• 英文别名: diethyl (1R,2S,3R,4S,5S)-5-formyl-2-(phenylmethoxycarbonylamino)bicyclo[2.2.1]heptane-2,3-dicarboxylate
• 化学式: C₂₂H₂₇NO₇
• 分子量: 417.459
• InChiKey: CJMMSKXTRAOKTN-JVOBEXOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R*,2S*,3R*,4S*,5S*)-2-benzyloxycarbonylamino-6-formylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester 、 甲基三苯基溴化膦 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 以65%的产率得到(1S*,2S*,3R*,4S*,5R*)-2-benzyloxycarbonylamino-5-vinylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester
  参考文献：
  名称：

  Identification of Selective Norbornane-Type Aspartate Analogue Inhibitors of the Glutamate Transporter 1 (GLT-1) from the Chemical Universe Generated Database (GDB)

  摘要：

  A variety of conformationally constrained aspartate and glutamate analogues inhibit the glutamate transporter 1 (GLT-1, also known as EAAT2). To expand the search for such analogues, a virtual library of aliphatic aspartate and glutamate analogues was generated starting from the chemical universe database GDB-11 which contains 26.4 million possible molecules up to 11 atoms of C. N. O, F, resulting in 101026 aspartate analogues and 151285 glutamate analogues. Virtual screening was realized by high-throughput docking to the glutamate binding site of the glutamate transporter homologue from Pyrococcus horikoshii (PDB code: 1XFH) using Autodock. Norbornane-type aspartate analogues were selected from the top-scoring virtual hits and synthesized. Testing and optimization led to the identification of (1R*,2R*,3S*,4R*,6R*)-2-amino-6-phenethyl-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid as a new inhibitor of GLT-1 with IC(50) = 1.4 mu M against GLT-1 and no inhibition of the related transporter EAAC1. The systematic diversification of ligands by enumeration with help of GDB followed by virtual screening, synthesis. and testing as exemplified here provides a general strategy For drug discovery.

  DOI：

  10.1021/jm100959g
• 作为产物：
  描述：

  一氧化碳 、 (1S*,2S*,3R*,4R*)-2-benzyloxycarbonylaminobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid diethyl ester 在 (acetylacetonato)dicarbonylrhodium (l) 、 氢气 作用下， 以 甲苯 为溶剂， 60.0 ℃ 、4.0 MPa 条件下， 反应 24.0h， 以30%的产率得到(1R*,2S*,3R*,4S*,6R*)-2-benzyloxycarbonylamino-6-formylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester
  参考文献：
  名称：

  Identification of Selective Norbornane-Type Aspartate Analogue Inhibitors of the Glutamate Transporter 1 (GLT-1) from the Chemical Universe Generated Database (GDB)

  摘要：

  A variety of conformationally constrained aspartate and glutamate analogues inhibit the glutamate transporter 1 (GLT-1, also known as EAAT2). To expand the search for such analogues, a virtual library of aliphatic aspartate and glutamate analogues was generated starting from the chemical universe database GDB-11 which contains 26.4 million possible molecules up to 11 atoms of C. N. O, F, resulting in 101026 aspartate analogues and 151285 glutamate analogues. Virtual screening was realized by high-throughput docking to the glutamate binding site of the glutamate transporter homologue from Pyrococcus horikoshii (PDB code: 1XFH) using Autodock. Norbornane-type aspartate analogues were selected from the top-scoring virtual hits and synthesized. Testing and optimization led to the identification of (1R*,2R*,3S*,4R*,6R*)-2-amino-6-phenethyl-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid as a new inhibitor of GLT-1 with IC(50) = 1.4 mu M against GLT-1 and no inhibition of the related transporter EAAC1. The systematic diversification of ligands by enumeration with help of GDB followed by virtual screening, synthesis. and testing as exemplified here provides a general strategy For drug discovery.

  DOI：

  10.1021/jm100959g