(1R*,2S*,3R*,4R*,6S*)-2-benzyloxycarbonylamino-6-styrylbicyclo[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*,4R*,6S*)-2-benzyloxycarbonylamino-6-styrylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester
• 英文别名: diethyl (1R,2S,3R,4R,6S)-6-[(E)-2-phenylethenyl]-2-(phenylmethoxycarbonylamino)bicyclo[2.2.1]heptane-2,3-dicarboxylate
• 化学式: C₂₉H₃₃NO₆
• 分子量: 491.584
• InChiKey: ILOQFIPOEKLWJQ-JBMJFGNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (1R*,2S*,3R*,4S*,6R*)-2-benzyloxycarbonylamino-6-formylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester 、 苄基三苯基氯化膦 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 生成 (1R*,2S*,3R*,4R*,6S*)-2-benzyloxycarbonylamino-6-styrylbicyclo[2.2.1]heptane-2,3-dicarboxylic acid diethyl ester 、 (1R*,2S*,3R*,4R*,6S*)-2-benzyloxycarbonylamino-6-styrylbicyclo[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

文献信息

• Identification of Selective Norbornane-Type Aspartate Analogue Inhibitors of the Glutamate Transporter 1 (GLT-1) from the Chemical Universe Generated Database (GDB)
  作者：Erika Luethi、Kong T. Nguyen、Marc Bürzle、Lorenz C. Blum、Yoshiro Suzuki、Matthias Hediger、Jean-Louis Reymond

  DOI：10.1021/jm100959g

  日期：2010.10.14

  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.