1,3'-dimethyl-1'H-spiro[imidazolidine-4,4'-quinazoline]-2,5,2'-trione | 28567-71-7

• 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: 1,3'-dimethyl-1'H-spiro[imidazolidine-4,4'-quinazoline]-2,5,2'-trione
• 英文别名: 3,3'-dimethylspiro[1H-quinazoline-4,5'-imidazolidine]-2,2',4'-trione
• CAS: 28567-71-7
• 化学式: C₁₂H₁₂N₄O₃
• 分子量: 260.252
• InChiKey: BVHCEVFMOQMYCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,3'-dimethyl-1'H-spiro[imidazolidine-4,4'-quinazoline]-2,5,2'-trione 在 sodium hydride 作用下， 反应 3.0h， 生成 1,1',3,3'-tetramethylspiro-2,2',5'(3'H)-trione
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00089a021
• 作为产物：
  描述：

  N-(methylcarbamoyl)isatin 在 盐酸 、 sodium hydride 、 三乙胺 作用下， 反应 7.5h， 生成 1,3'-dimethyl-1'H-spiro[imidazolidine-4,4'-quinazoline]-2,5,2'-trione
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1021/jm00089a021

文献信息

• Quinazolinone compounds and processes for the preparation thereof
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0204534A2

  公开（公告）日：1986-12-10

  There are described novel quinazolinone compounds of the formula: wherein R is hydrogen atom or a lower alkyl, R1 is a lower alkyl, a substituted or unsubstituted phenyl or an aralkyl, and R2, R3, R4 and R5 are the same or different and are each hydrogen atom, a halogen atom, a lower alkyl, a lower alkoxy, a lower alkoxycarbonyl or a lower alkoxycarbonyl-lower alkenyl, ortwo adjacent groups of R2, R3, R4 and R5 when taken together form methylenedioxy and the other two are hydrogen atom, and salts thereof. The compounds are useful for the prophylaxis and treatment of various diabetic complications. There are also disclosed processes for the preparation of compound of formula I, and pharmaceutical compositions containing such compound as an active ingredient.

  描述了式中的新型喹唑啉酮化合物： 其中 R 是氢原子或低级烷基，R1 是低级烷基、取代或未取代的苯基或芳烷基，R2、R3、R4 和 R5 相同或不同，并且各自是氢原子、卤素原子、低级烷基、低级烷氧基、低级烷氧羰基或低级烷氧羰基-低级烯基，或者 R2、R3、R4 和 R5 的两个相邻基团在一起时形成亚甲基二氧基，另外两个是氢原子，以及它们的盐。这些化合物可用于预防和治疗各种糖尿病并发症。此外，还公开了制备式 I 化合物的工艺和含有此类化合物作为活性成分的药物组合物。
• US4762839A
  申请人：——

  公开号：US4762839A

  公开（公告）日：1988-08-09
• 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.