1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮,7-[(2S,3S,4R,5R)-3,4-二羟基-5-(羟甲基)-2-吡咯烷基]-,盐酸(1:1) | 774516-60-8

• 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
• 中文名称: 1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮,7-[(2S,3S,4R,5R)-3,4-二羟基-5-(羟甲基)-2-吡咯烷基]-,盐酸(1:1)
• 中文别名: (1R)-2-氨基双环[2.2.1]庚烷-2,3-二甲酸
• 英文名称: (1S*,2R*,3S*,4R*)-2-amino-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid
• 英文别名: (1R,2S,3R,4S)-2-Aminobicyclo[2.2.1]heptane-2,3-dicarboxylic acid
• CAS: 774516-60-8
• 化学式: C₉H₁₃NO₄
• 分子量: 199.207
• InChiKey: HBLCKYRWQMAQCD-LHKPINMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮,7-[(2S,3S,4R,5R)-3,4-二羟基-5-(羟甲基)-2-吡咯烷基]-,盐酸(1:1) 在 盐酸 作用下， 以 水 为溶剂， 以13 mg的产率得到(1R,2S,3R,4S)-2-Amino-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid; hydrochloride
  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：

  (1R*,2R*,3S*,4S*)-2-benzyloxycarbonylaminobicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 1.5h， 生成 1H-吡咯并[3,2-d]嘧啶-2,4(3H,5H)-二酮,7-[(2S,3S,4R,5R)-3,4-二羟基-5-(羟甲基)-2-吡咯烷基]-,盐酸(1:1)
  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.