2,4-dioxo-1,3-diaza-spiro[4.4]nonane-6-carboxylic acid | 7153-58-4

• 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[4.4]nonane-6-carboxylic acid
• 英文别名: Hydantoin-5-spirocyclopentan-carbonsaeure-(2')；2,4-Dioxo-1,3-diazaspiro[4.4]nonane-6-carboxylic acid；2,4-dioxo-1,3-diazaspiro[4.4]nonane-9-carboxylic acid
• CAS: 7153-58-4
• 化学式: C₈H₁₀N₂O₄
• 分子量: 198.178
• InChiKey: WACOSHVKEJALEK-UHFFFAOYSA-N

物化性质

• 熔点：
  225-226 °C(Solvent: Water)
• 密度：
  1.53±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 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[4.4]nonane-6-carboxylic acid 在 barium dihydroxide 作用下， 以 水 为溶剂， 生成 1-氨基环戊烷-1,2-二羧酸
  参考文献：
  名称：

  428. 1-氨基环戊烷羧酸的一些衍生物和有关化合物

  摘要：

  DOI：

  10.1039/jr9600002119
• 作为产物：
  描述：

  2,4-dioxo-1,3-diaza-spiro[4.4]nonane-6-carboxylic acid ethyl ester 在 盐酸 作用下， 生成 2,4-dioxo-1,3-diaza-spiro[4.4]nonane-6-carboxylic acid
  参考文献：
  名称：

  Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor necrosis factor-α converting enzyme (TACE)

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2006.11.089

文献信息

• 428. Some derivatives of 1-aminocyclopentanecarboxylic acid and related compounds
  作者：T. A. Connors、W. C. J. Ross

  DOI：10.1039/jr9600002119

  日期：——
• 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.
• 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.