3'-Hydroxyspiro-2,2',5(3'H)-trione | 134540-04-8

• 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: 3'-Hydroxyspiro-2,2',5(3'H)-trione
• 英文别名: 3-hydroxyspiro[1H-quinazoline-4,5'-imidazolidine]-2,2',4'-trione
• CAS: 134540-04-8
• 化学式: C₁₀H₈N₄O₄
• 分子量: 248.198
• InChiKey: JXZSEWUYZXBMOM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-ethoxycarbonylisatin 在 氢氧化钾 、 盐酸羟胺 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 21.0h， 生成 3'-Hydroxyspiro-2,2',5(3'H)-trione
  参考文献：
  名称：

  Quinazolin-2-ones having a spirohydantoin ring. II. Synthesis of several spiro(imidazolidine-4,4'(1'H)-quinazoline)-2,2',5(3'H)-triones via 5-hydroxyhydantoin derivatives.

  摘要：

  将 1-乙氧基羰基靛红 (1b) 与脲反应，得到 5-(2-乙氧基羰基氨基苯基)-5-羟基海因 (4b)，收率很高。用几种胺直接处理 4b，可得到相应的螺[咪唑烷-4，4'(1'H)-喹唑啉]-2，2'，5(3'H)-三酮衍生物（7a-d），收率中等。5-乙氧基和 5-乙硫基海因 5a, d 也可合成 3-未取代和 3-甲基螺喹唑啉-2-酮衍生物 7a, b，这些衍生物又可通过乙醇或乙硫醇与 4b 在一定量的硫酸催化下反应而轻松获得。

  DOI：

  10.1248/cpb.39.626

文献信息

• Quinazolin-2-ones having a spirohydantoin ring. II. Synthesis of several spiro(imidazolidine-4,4'(1'H)-quinazoline)-2,2',5(3'H)-triones via 5-hydroxyhydantoin derivatives.
  作者：Masafumi YAMAGISHI、Yoshihisa YAMADA、Ken-ichi OZAKI、Junichi TANI、Mamoru SUZUKI

  DOI：10.1248/cpb.39.626

  日期：——

  Reaction of 1-ethoxycarbonylisatin (1b) with urea gave 5-(2-ethoxycarbonylaminophenyl)-5-hydroxyhydantoin (4b) in a good yield. Treatment of 4b with several amines directly gave the corresponding spiro[imidazolidine-4, 4'(1'H)-quinazoline]-2, 2', 5(3'H)-trione derivatives (7a-d) in moderate yields. 3-Unsubstituted and 3-methylspiroquinazolin-2-one derivatives 7a, b were also synthesized from 5-ethoxy and 5-ethylthiohydantoins 5a, d, which in turn were easily obtained by the reaction of either ethanol or ethylmercaptan with 4b in the presence of a catalytic amount of sulfuric acid.

  将 1-乙氧基羰基靛红 (1b) 与脲反应，得到 5-(2-乙氧基羰基氨基苯基)-5-羟基海因 (4b)，收率很高。用几种胺直接处理 4b，可得到相应的螺[咪唑烷-4，4'(1'H)-喹唑啉]-2，2'，5(3'H)-三酮衍生物（7a-d），收率中等。5-乙氧基和 5-乙硫基海因 5a, d 也可合成 3-未取代和 3-甲基螺喹唑啉-2-酮衍生物 7a, b，这些衍生物又可通过乙醇或乙硫醇与 4b 在一定量的硫酸催化下反应而轻松获得。
• Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors
  作者：Masafumi Yamagishi、Yoshihisa Yamada、Kenichi Ozaki、Masaaki Asao、Ryo Shimizu、Mamoru Suzuki、Mamoru Matsumoto、Yuzo Matsuoka、Kazuo Matsumoto

  DOI：10.1021/jm00089a021

  日期：1992.5

  A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'-halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'-chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure-activity relationships in this series are also discussed.