4-chloro-N-benzylisatoic anhydride | 35709-36-5

• 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: 4-chloro-N-benzylisatoic anhydride
• 英文别名: 7-chloro-N-benzylisatoic anhydride；N-benzyl-4-chloroisatoic anhydride；1-Benzyl-7-chloro-2H-3,1-benzoxazin-2,4(1H)-dion；1-benzyl-7-chloro-1H-benzo[d][1,3]oxazine-2,4-dione；1-Benzyl-7-chloro-3,1-benzoxazine-2,4-dione
• CAS: 35709-36-5
• 化学式: C₁₅H₁₀ClNO₃
• 分子量: 287.702
• InChiKey: JANSLFFUIIRRNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 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：

  4-chloro-N-benzylisatoic 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-benzyl-7-chloro-4-hydroxy-N'-octanoyl-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：

  2-氨基-4-氯苯甲酸 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.58h， 生成 4-chloro-N-benzylisatoic anhydride
  参考文献：
  名称：

  [EN] NOVEL HETEROCYCLIC COMPOUND
  [FR] NOUVEAU COMPOSÉ HÉTÉROCYCLIQUE
  [ZH] 一种新型杂环化合物

  摘要：

  本发明涉及一种新型杂环化合物；具体地，本发明提供式(I)所示的化合物或其药学上可接受的盐、溶剂化物、多晶型物或异构体，以及包含其的药物组合物，以及其在制备治疗跟MAT2A相关的疾病的药物中的用途。

  公开号：

  WO2023185811A1

文献信息

• 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。
• Lithiated Thiolactams: New Synthesis of Azacycloalka[2,3-<i>b</i>]quinolin-4-ones
  作者：Hiroki Takahata、Nahoko Hamada、Takao Yamazaki

  DOI：10.1055/s-1986-31646

  日期：——

  Lithiated enamines, generated from cyclic thioimidates by treatment with lithium diisopropylamide, react with N-alkylisatoic anhydrides to afford azacycloalka[2,3-b]quinolin-4-ones.

  通过二异丙基锂酰胺处理从环硫代亚胺酸盐中生成的锂化烯胺与 N-烷基异酸酐反应生成氮杂环烷并[2,3-b]喹啉-4-酮。
• TAKAHATA, HIROKI;HAMADA, NAHOKO;YAMAZAKI, TAKAO, SYNTHESIS, BRD, 1986, N 5, 388-390
  作者：TAKAHATA, HIROKI、HAMADA, NAHOKO、YAMAZAKI, TAKAO

  DOI：——

  日期：——
• HARDTMANN G. E.; KOLETAR G.; PFISTER O. R.; GOGERTY J. H.; IORIO L. C., J. MED. CHEM. <JMCM-AR>, 1975, 18, NO 5, 447-453
  作者：HARDTMANN G. E.、 KOLETAR G.、 PFISTER O. R.、 GOGERTY J. H.、 IORIO L. C.

  DOI：——

  日期：——
• Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases
  作者：Valle Palomo、Daniel I. Perez、Carlos Roca、Cara Anderson、Natalia Rodríguez-Muela、Concepción Perez、Jose A. Morales-Garcia、Julio A. Reyes、Nuria E. Campillo、Ana M. Perez-Castillo、Lee L. Rubin、Lubov Timchenko、Carmen Gil、Ana Martinez

  DOI：10.1021/acs.jmedchem.7b00395

  日期：2017.6.22

  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.