3-methyl-spiro<1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine>-2,2',5'-trione | 107583-12-0

• 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-methyl-spiro<1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine>-2,2',5'-trione
• 英文别名: 3'-Methylspiro-2,2',5(3'H)-trione；3-methyl-spiro[1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine]-2,2',5'-trione；3-methylspiro[1H-quinazoline-4,5'-imidazolidine]-2,2',4'-trione
• CAS: 107583-12-0
• 化学式: C₁₁H₁₀N₄O₃
• 分子量: 246.225
• InChiKey: WTRHXNHBRZONAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  90.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methyl-spiro<1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine>-2,2',5'-trione 在 sodium hydride 作用下， 反应 4.5h， 生成 3-acetyl-1-<(benzyloxy)methyl>-1',3'-dimethylspiro-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 sodium hydroxide 、 溶剂黄146 、 sodium nitrite 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 3-methyl-spiro<1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine>-2,2',5'-trione
  参考文献：
  名称：

  Quinazolin-2-ones having a spirohydantoin ring. I. Synthesis of spiro(1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine)-2,2',5'-trione by reaction of 1-carbamoylisatin with urea or guanidine.

  摘要：

  在 1, 8-二氮杂双环[5.4.0]十一-7-烯（DBU）存在下，1-甲基氨基甲酰化（4）与尿素反应，得到 4-羟基-3-甲基-4-脲羰基-1, 2, 3, 4-四氢喹唑啉-2-酮（5）。0]十一碳-7-烯（DBU）的条件下与脲反应，得到 4-羟基-3-甲基-4-脲羰基-1，2，3，4-四氢喹唑啉-2-酮（5），用 10% HCl 很容易将其环化，得到螺海因衍生物；3-甲基-螺[1，2，3，4-四氢喹唑啉-4，4'-咪唑烷]-2，2'，5'-三酮（6）。用类似的方法，通过 4 与胍的反应制备了 2'-亚氨基-3-甲基-螺[1，2，3，4-四氢喹唑啉-4.4'-咪唑烷]-2，5'-二酮（8），通过在乙酸中使用亚硝酸钠处理，8 进一步转化为螺海因化合物 6。

  DOI：

  10.1248/cpb.38.2926

文献信息

• Quinazolinone copmpounds useful for the prophyloxis and treatment of
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04762839A1

  公开（公告）日：1988-08-09

  Novel quinazolinone compounds of the formula: ##STR1## wherein R is hydrogen atom or a lower alkyl, R.sup.1 is a lower alkyl, a substituted or unsubstituted phenyl or an aralkyl, and R.sup.2, R.sup.3, R.sup.4 and R.sup.5 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, or two adjacent groups of R.sup.2,R.sup.3, R.sup.4 and R.sup.5 when taken together form methylenedioxy and the other two are hydrogen atom, and a salt thereof, which are useful for the prophylaxis and treatment of various diabetic complications, and processes for the preparation thereof, and a pharmaceutical composition containing said compound as an active ingredient.

  新型喹唑啉酮化合物的化学式为：##STR1## 其中R为氢原子或较低的烷基，R.sup.1为较低的烷基，取代或未取代的苯基或芳基烷基，R.sup.2、R.sup.3、R.sup.4和R.sup.5相同或不同，分别为氢原子、卤原子、较低的烷基、较低的烷氧基、较低的烷氧羰基或较低的烷氧羰基-较低的烯基，或者当R.sup.2、R.sup.3、R.sup.4和R.sup.5中的两个相邻基团结合形成亚甲二氧基时，另外两个为氢原子，以及其盐。这些化合物对于预防和治疗各种糖尿病并发症非常有用，以及其制备方法，以及含有该化合物作为活性成分的药物组合物。
• Quinazolin-2-ones having a spirohydantoin ring. I. Synthesis of spiro(1,2,3,4-tetrahydroquinazoline-4,4'-imidazolidine)-2,2',5'-trione by reaction of 1-carbamoylisatin with urea or guanidine.
  作者：Masafumi YAMAGISHI、Ken-ichi OZAKI、Hiroshi OHMIZU、Yoshihisa YAMADA、Mamoru SUZUKI

  DOI：10.1248/cpb.38.2926

  日期：——

  Reaction of 1-methylcarbamoylisation (4) with urea in the presence of 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave 4-hydroxy-3-methyl-4-ureidocarbonyl-1, 2, 3, 4-tetrahydroquinazolin-2-one (5), which was easily cyclized with 10% HCl to afford a spirohydantoin derivative; 3-methyl-spiro[1, 2, 3, 4-tetrahydroquinazoline-4, 4'-imidazolidine]-2, 2', 5'-trione (6). In a similar manner, 2'-imino-3-methyl-spiro[1, 2, 3, 4-tetrahydroquinazoline-4.4'-imidazolidine]-2, 5'-dione (8) was prepared by the reaction of 4 with guanidine, and 8 was further converted to the spirohydantoin compound 6 by treatment with sodium nitrite in acetic acid.

  在 1, 8-二氮杂双环[5.4.0]十一-7-烯（DBU）存在下，1-甲基氨基甲酰化（4）与尿素反应，得到 4-羟基-3-甲基-4-脲羰基-1, 2, 3, 4-四氢喹唑啉-2-酮（5）。0]十一碳-7-烯（DBU）的条件下与脲反应，得到 4-羟基-3-甲基-4-脲羰基-1，2，3，4-四氢喹唑啉-2-酮（5），用 10% HCl 很容易将其环化，得到螺海因衍生物；3-甲基-螺[1，2，3，4-四氢喹唑啉-4，4'-咪唑烷]-2，2'，5'-三酮（6）。用类似的方法，通过 4 与胍的反应制备了 2'-亚氨基-3-甲基-螺[1，2，3，4-四氢喹唑啉-4.4'-咪唑烷]-2，5'-二酮（8），通过在乙酸中使用亚硝酸钠处理，8 进一步转化为螺海因化合物 6。
• 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。
• 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。
• YAMADA, YOSHIHISA;MATSUOKA, YUZO;MATSUMOTO, MAMORU
  作者：YAMADA, YOSHIHISA、MATSUOKA, YUZO、MATSUMOTO, MAMORU

  DOI：——

  日期：——