N-(methylcarbamoyl)isatin | 21381-47-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-(methylcarbamoyl)isatin
• 英文别名: 1-(methylcarbamoyl)isatin；1-methylcarbamoylisatin；2,3-dioxo-2,3-dihydro-indole-1-carboxylic acid methylamide；1-Methylcarbamoyl-isatin；N-methyl-2,3-dioxoindole-1-carboxamide
• CAS: 21381-47-5
• 化学式: C₁₀H₈N₂O₃
• 分子量: 204.185
• InChiKey: DPFWDTPLVNXXST-UHFFFAOYSA-N

物化性质

• 熔点：
  149-150 °C
• 密度：
  1.431±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  66.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(methylcarbamoyl)isatin 在 钯 盐酸 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 乙醇 为溶剂， 25.0~80.0 ℃ 、310.27 kPa 条件下， 反应 15.5h， 生成 3-acetyl-1'-isobutyl-3'-methylspiro-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：

  2-羟基亚氨基-n-苯乙酰胺 在 硫酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 N-(methylcarbamoyl)isatin
  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 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. III. A General and Efficient Synthesis of 3'-Substituted Spiro(imidazolidine-4,4'(1'H)-quinazoline)-2,2',5(3'H)-triones.
  作者：Masafumi YAMAGISHI、Ken-ichi OZAKI、Yoshihisa YAMADA、Tadamasa DA-TE、Kimio OKAMURA、Mamoru SUZUKI

  DOI：10.1248/cpb.39.1694

  日期：——

  The reaction of 1-carbamoylisatins 2 with 2-ethyl-2-isothiourea hydrobromide in the presence of triethylamine followed by acid-catalyzed cyclization of the resulting 4-(2-ethyl-2-isothioureido)carbonyl-3, 4-dihydro-4-hydroxy-2(1H)-quinazolinones 7 provides a general and high-yielding route to 3'-substituted spiro[imidazolidine-4, 4'(1'H)-quinazoline]-2, 2'5(3'H)-triones 8.

  在三乙胺存在下，1-氨基甲酰基异沙丁鱼苷 2 与 2-乙基-2-异硫脲氢溴酸盐反应，然后在酸催化下环化生成 4-(2-乙基-2-异硫脲基)羰基-3.4-二氢-4-羟基-2(1H)-喹唑啉酮 7、4-二氢-4-羟基-2(1H)-喹唑啉酮 7 提供了一条通向 3'-取代的螺[咪唑烷-4，4'(1'H)-喹唑啉]-2，2'5(3'H)-三酮 8 的通用高产路线。
• 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。
• 3-Acyloxymethyl-cephem compounds
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04166178A1

  公开（公告）日：1979-08-28

  Novel 3-acyloxymethyl-cephem compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen or an acyl group; X is a divalent group consisting of a carbon chain having 2 to 3 carbon atoms and a carbonyl or sulfonyl group at one terminal end thereof, said divalent group being either substituted or unsubstituted on the carbon chain; and Z is an organic acid residue, and salts thereof were found to be useful as starting materials for preparing cephalosporins of the formula: ##STR2## wherein R.sup.2 stands for a residue of a nucleophilic compound and R.sup.1 has the same meaning as above.

  化合物的名称为Novel 3-acyloxymethyl-cephem，分子式为： ##STR1## 其中R1为氢或酰基；X为二价基团，由具有2到3个碳原子的碳链和一个在其末端具有羰基或磺酰基的基团组成，该二价基团在碳链上可以是取代或未取代的；Z为有机酸残基，其盐也可用作制备下式中头孢菌素的起始材料： ##STR2## 其中R2代表亲核化合物的残基，R1具有与上述相同的含义。
• Derivatives of 7-aminocephalosporanic acid
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04224441A1

  公开（公告）日：1980-09-23

  Novel 3-acyloxymethyl-cephem compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen or an acyl group; X is a divalent group consisting of a carbon chain having 2 to 3 carbon atoms and a carbonyl or sulfonyl group at one terminal end thereof, said divalent group being either substituted or unsubstituted on the carbon chain; and Z is an organic acid residue, and salts thereof were found to be useful as starting materials for preparing cephalosporins of the formula: ##STR2## wherein R.sup.2 stands for a residue of a nucleophilic compound and R.sup.1 has the same meaning as above.

  化合物的名称为Novel 3-acyloxymethyl-cephem，分子式为：##STR1## 其中R.sup.1是氢或酰基；X是一个二价基团，由一个碳链和一个羰基或磺酰基组成，该二价基团在碳链上是取代或未取代的；Z是一个有机酸残基。这些化合物及其盐被发现可用作制备头孢菌素的起始材料，头孢菌素的分子式为：##STR2## 其中R.sup.2代表亲核化合物残基，R.sup.1具有与上述相同的含义。