2-cyano-2-hydroxycyclopentanecarboxylic acid | 1378717-66-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-cyano-2-hydroxycyclopentanecarboxylic acid
• 英文别名: 2-Cyano-2-hydroxycyclopentane-1-carboxylic acid
• CAS: 1378717-66-8
• 化学式: C₇H₉NO₃
• 分子量: 155.153
• InChiKey: IGOJENWGCOBCRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  81.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氧代环戊羧酸乙酯 、 碳酸氢铵 、 potassium cyanide 在 水 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以66 mg的产率得到2-cyano-2-hydroxycyclopentanecarboxylic acid
  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