2,4-dioxo-1,3-diaza-spiro[4.5]decane-6-carboxylic acid | 947-10-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 2,4-dioxo-1,3-diaza-spiro[4.5]decane-6-carboxylic acid
• 英文别名: 2-Carboxy-cyclohexanspiro-5'-hydantoin；2,4-Dioxo-1,3-diazaspiro[4.5]decane-6-carboxylic acid
• CAS: 947-10-4
• 化学式: C₉H₁₂N₂O₄
• 分子量: 212.205
• InChiKey: OTAKKISWKHJBKV-UHFFFAOYSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-dioxo-1,3-diaza-spiro[4.5]decane-6-carboxylic acid 在 盐酸 、 水 作用下， 反应 168.0h， 以36%的产率得到1-amino-cyclohexane-1,2-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：

  2,4-二氧代-1,3-二氮杂螺[4.5]癸烷-6-羧酸乙酯 在 盐酸 、 水 作用下， 反应 48.0h， 以81 mg的产率得到2,4-dioxo-1,3-diaza-spiro[4.5]decane-6-carboxylic 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

文献信息

• Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor necrosis factor-α converting enzyme (TACE)
  作者：James E. Sheppeck、John L. Gilmore、Anle Yang、Xiao-Tao Chen、Chu-Biao Xue、John Roderick、Rui-Qin Liu、Maryanne B. Covington、Carl P. Decicco、James J.-W. Duan

  DOI：10.1016/j.bmcl.2006.11.089

  日期：2007.3

  A series of novel hydantoins was designed and synthesized as structural alternatives to hydroxamate inhibitors of TACE. 5-Mono- and di-substituted hydantoins exhibited activity with IC50 values of 11-60 nM against porcine TACE in vitro and excellent selectivity against other MMPs.