ethyl (2Z)-cyano(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetate | 13481-44-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: ethyl (2Z)-cyano(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetate
• 英文别名: 1-α-Cyan-α-ethoxycarbonyl-methylen-3-oxo-isoindolin；3-(Ethoxycarbonyl-cyanmethylen)-phtalimidin；ethyl (2Z)-2-cyano-2-(3-oxoisoindol-1-ylidene)acetate
• CAS: 13481-44-2
• 化学式: C₁₃H₁₀N₂O₃
• 分子量: 242.234
• InChiKey: QMWZCYFGJGTVQG-KHPPLWFESA-N

物化性质

• 熔点：
  170 °C
• 沸点：
  476.9±45.0 °C(Predicted)
• 密度：
  1.324±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl (2Z)-cyano(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetate 在 potassium carbonate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 Ethyl 2-(2-butyl-1-cyano-3-oxoisoindol-1-yl)-2-cyanoacetate
  参考文献：
  名称：

  Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents

  摘要：

  Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.

  DOI：

  10.1021/jm00102a016
• 作为产物：
  描述：

  2-氰基苯甲酸甲酯 在 氨 、 sodium methylate 、 sodium ethanolate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 9.0h， 生成 ethyl (2Z)-cyano(3-oxo-2,3-dihydro-1H-isoindol-1-ylidene)acetate
  参考文献：
  名称：

  环状酰基am作为与丙二腈在碱介导的反应中完全取代的吡啶环形成的意外C4供体

  摘要：

  一个新的步骤中，对于完全取代的吡啶的合成伪四组分的方法通过将3-氨基1的环状酰基脒的开环ħ与丙二腈在反应过程中异吲哚-1-酮和其氮杂类似物据报道在甲醇钠存在下，随后吡啶闭环。该方法允许在温和的反应条件下以高收率一步制备先前未知的2-（吡啶-4-基）（杂）芳基羧酰胺。

  DOI：

  10.1016/j.tetlet.2019.06.038

文献信息

• DUNN, A. D., J. HETEROCYCL. CHEM., 1984, 21, N 4, 965-968
  作者：DUNN, A. D.

  DOI：——

  日期：——
• Novel spirosuccinimides with incorporated isoindolone and benzisothiazole 1,1-dioxide moieties as aldose reductase inhibitors and antihyperglycemic agents
  作者：Jay Wrobel、Arlene Dietrich、Shiela A. Woolson、Jane Millen、Michael McCaleb、Maria C. Harrison、Thomas C. Hohman、Janet Sredy、Donald Sullivan

  DOI：10.1021/jm00102a016

  日期：1992.11

  Compounds from two novel series of spirosuccinimides were prepared. Analogs of series 2 possessed a spiro-fused isoindolone moiety while those of series 3 contained a spiro-fused benzisothiazole S,S-dioxide group. These compounds were evaluated as aldose reductase inhibitors (ARI) in vitro by their ability to inhibit glyceraldehyde reduction using a partially purified bovine lens aldose reductase preparation and in vivo as inhibitors of galactitol accumulation in the lens, sciatic nerve, and diaphragm of galactose-fed rats. Many members from the isoindolone series 2, particularly those containing an isoindolone N-methyl moiety, showed good in vitro and in vivo potency. The most potent member, the 6-chloro analog 32, was resolved, and aldose reductase activity was found to reside almost exclusively in the (+)-enantiomer. Compound 32 was approximately equipotent in the sciatic nerve of the galactose-fed rat to other cyclic imide ARI's of similar in vitro activity, namely sorbinil and ADN-138 and also to tolrestat, an acetic acid-based ARI (ED50's 4-8 mg/kg). Compounds from both series, 2 and 3, were also found to lower plasma glucose levels of genetically obese db/db and ob/ob mice with potency similar to that of ciglitazone. However, members from these series failed to lower insulin levels of the ob/ob mouse at the doses tested.
• Cyclic acyl amidines as unexpected C4-donors for fully substituted pyridine ring formation in the base mediated reaction with malononitrile
  作者：Volodymyr Tkachuk、Vladyslava Merkulova、Iryna Omelchenko、Axelle Arrault、Olga Hordiyenko

  DOI：10.1016/j.tetlet.2019.06.038

  日期：2019.7

  A new one-step, pseudo four-component approach for the synthesis of fully substituted pyridines via ring-opening of the cyclic acyl amidine of 3-amino-1H-isoindol-1-one and its aza-analogues during the reaction with malononitrile in the presence of sodium methoxide, followed by pyridine ring closure is reported. This method allows the one-step preparation of previously unknown 2-(pyridin-4-yl)(hetero)aryl

  一个新的步骤中，对于完全取代的吡啶的合成伪四组分的方法通过将3-氨基1的环状酰基脒的开环ħ与丙二腈在反应过程中异吲哚-1-酮和其氮杂类似物据报道在甲醇钠存在下，随后吡啶闭环。该方法允许在温和的反应条件下以高收率一步制备先前未知的2-（吡啶-4-基）（杂）芳基羧酰胺。