N-(cyclopropylmethyl)isatoic anhydride | 42239-89-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: N-(cyclopropylmethyl)isatoic anhydride
• 英文别名: 1-(cyclopropylmethyl)-3,1-benzoxazine-2,4-dione
• CAS: 42239-89-4
• 化学式: C₁₂H₁₁NO₃
• 分子量: 217.224
• InChiKey: CMVNCNXRMWPIOD-UHFFFAOYSA-N

物化性质

• 熔点：
  118-121 °C
• 沸点：
  354.4±25.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(cyclopropylmethyl)isatoic anhydride 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.55h， 生成 1-(cyclopropylmethyl)-N'-dodecanoyl-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbohydrazide
  参考文献：
  名称：

  Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases

  摘要：

  Glycogen synthase kinase 3 beta (GSK-3 beta) is a central target in several unmet diseases. To increase the specificity of GSK-3 beta inhibitors in chronic treatments, we developed small molecules allowing subtle modulation of GSK-3 beta activity. Design synthesis, structure activity relationships, and binding mode of quinoline-3-carbohydrazide derivatives as allosteric modulators of GSK-3 beta are presented here. Furthermore, we show how allosteric binders may overcome the beta-catenin side effects associated with strong GSK-3 beta inhibition. The therapeutic potential of some of these modulators has been tested in human samples from patients with congenital myotonic dystrophy type 1 (CDM1) and spinal it atrophy (SMA) patients. We found that compound 53 improves delayed myogenesis in CDM1 myoblasts, while compounds 1 and 53 have neuroprotective properties in SMA-derived cells. These findings suggest that the allosteric modulators of GSK-3 beta may be used for future development of drugs for DM1, SMA, and other chronic diseases where GSK-3 beta inhibition exhibits therapeutic effects.

  DOI：

  10.1021/acs.jmedchem.7b00395
• 作为产物：
  描述：

  靛红酸酐 、 溴甲基环丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 以41%的产率得到N-(cyclopropylmethyl)isatoic anhydride
  参考文献：
  名称：

  HAT亚微摩尔抑制剂1,4-苯并二氮杂-2-酮和喹唑啉-2,4-二酮支架的鉴定与开发

  摘要：

  合成了一个1,4-苯并二氮杂卓的文库，并评估了其对布鲁氏锥虫（人类非洲锥虫病（HAT）的致病性寄生虫）的活性。这些衍生物中最有效的MIC值为0.97μM。本文中我们报告了上述化合物的设计，合成和生物学评估。

  DOI：

  10.1016/j.bmc.2012.08.049

文献信息

• One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction
  作者：Zi-Xuan Wang、Jia-Chen Xiang、Miao Wang、Jin-Tian Ma、Yan-Dong Wu、An-Xin Wu

  DOI：10.1021/acs.orglett.8b02667

  日期：2018.10.19

  The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation

  使用三组分反应可实现一锅法合成乙二胺及其类似物。通过连续的双环化，容易将具有良好官能团耐受性的各种容易获得的底物掺入具有生物活性的喹唑啉代咔啉主链中。三乙氧基甲烷作为助溶剂的使用对于这种快速而直接的转化至关重要。
• The chemistry of 2<i>H</i>-3,1-benzoxazine-2,4(1<i>H</i>)dione (isatoic anhydrides) 1. The synthesis of<i>N</i>-substituted 2<i>H</i>-3,1-benzoxazine-2,4(1<i>H</i>)diones
  作者：Goetz E. Hardtmann、Gabor Koletar、Oskar R. Pfister

  DOI：10.1002/jhet.5570120325

  日期：1975.6

  Three methods for the preparation of N-substituted 2H-3,1-benzoxazine-2,4(1H)diones (isatoic anhydrides) (1) utilizing 2-chloro-, 2-nitrobenzoic acids and N-unsubstituted isatoic anhydrides as starting materials, are described.

  三种制备N-取代的2 H -3,1-苯并恶嗪-2,4（1 H）二酮（乙酸酐）的方法（1）使用2-氯-，2-硝基苯甲酸和N-未取代的等角酸酐作为制备方法描述了起始材料。
• Heterocyclic GSK-3 Allosteric Modulators
  申请人：Consejo Superior de Investigaciones Cientificas (CSIC)

  公开号：US20150057311A1

  公开（公告）日：2015-02-26

  The present invention relates to heterocyclic substituted quinoline derivatives as allosteric inhibitors of the glycogen synthase kinase-3 (GSK-3) enzyme. Therefore, these compounds are useful for the manufacturing of a medicament designed for the treatment and/or prevention of diseases wherein GSK-3 is involved, such as neurodegenerative diseases, inflammatory diseases, cancer, diabetes, and to promote various regenerative processes.

  本发明涉及杂环取代喹啉衍生物作为糖原合成酶激酶-3 (GSK-3) 酶的变构抑制剂。因此，这些化合物可用于制造用于治疗和/或预防 GSK-3 参与的疾病的药物，例如神经退行性疾病、炎症性疾病、癌症、糖尿病，以及促进各种再生过程。
• The chemistry of 2<i>H</i>-3,1-benzoxazine-2,4-(1<i>H</i>)dione (isatoic anhydride) 5. Synthesis of the [1]benzopyrano[3,2-<i>c</i>]quinoline ring system
  作者：Gary M. Coppola、Goetz E. Hardtmann

  DOI：10.1002/jhet.5570160448

  日期：1979.6

  The reaction of isatoic anhydrides with the anion derived from ethyl o-fluorobenzoylacetate to furnish [1]benzopyrano-[3,2-c]quinolines is described. An analogous reaction with 3-azaisatoic anhydride furnishes 1b, or with tricyclic anhydride 3, system 4 is isolated. Spectral data is also discussed.

  描述了等位酸酐与衍生自邻氟苯甲酰基乙酸乙酯的阴离子反应以提供[1]苯并吡喃基-[3,2- c ]喹啉。分离了与3-氮杂酸酐酸酐1b或与三环酸酐3的类似反应，系统4。还讨论了光谱数据。
• [4 + 2]-Annulation of Prop-2-ynylsulfonium Salts and Isatoic Anhydrides: Access to 3-Methylthio-4-quinolones
  作者：Qinfang Chen、Yihao Pan、Tingting Yue、Weiran Yang、Hua Liu、Jing Zheng

  DOI：10.1021/acs.orglett.0c02173

  日期：2020.8.7

  An unparalleled [4 + 2]-annulation of prop-2-ynylsulfonium salts with isatoic anhydrides was developed, affording a series of 4-quinolones with a alkylthio group in medium to good yields under mild conditions. In this reaction type, the prop-2-ynylsulfonium salt serves as a C2 synthon and sulfide does not act as a leaving group, providing facile access to organosulfur compounds. The resulting quinolone

  开发了无与伦比的[4 + 2]丙-2-炔基salts盐与isatoic酸酐，在温和条件下以中等至良好收率提供了一系列带有烷硫基的4-喹诺酮。在这种反应类型中，丙-2-炔基salt盐充当C2合成子，硫化物不充当离去基团，提供了轻松接触有机硫化合物的途径。所得的喹诺酮产物可以进一步转化为多种合成上有用的化合物。