1-(1,3-苯并二氧代l-5-甲基)-1H-吲哚-2,3-二酮 | 354781-32-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: 1-(1,3-苯并二氧代l-5-甲基)-1H-吲哚-2,3-二酮
• 英文名称: 1-(benzo[d][1,3]dioxol-5-ylmethyl)indoline-2,3-dione
• 英文别名: 1-(1,3-benzodioxol-5-ylmethyl)-1H-indole-2,3-dione；1-(1,3-benzodioxol-5-ylmethyl)indole-2,3-dione
• CAS: 354781-32-1
• 化学式: C₁₆H₁₁NO₄
• mdl: MFCD01957483
• 分子量: 281.268
• InChiKey: IAAUXYRLARWYTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-氨基苯基)吡咯 、 1-(1,3-苯并二氧代l-5-甲基)-1H-吲哚-2,3-二酮 以 乙醇 为溶剂， 反应 11.0h， 以96%的产率得到1-(benzo[d][1,3]dioxol-5-ylmethyl)-5'H-spiro[indoline-3,4'-pyrrolo[1,2-a]quinoxalin]
  参考文献：
  名称：

  Discovery of pyrrolospirooxindole derivatives as novel cyclin dependent kinase 4 (CDK4) inhibitors by catalyst-free, green approach

  摘要：

  Aiming to develop a new target for the anticancer treatment, a series of 5'H-spiro[indoline-3,4'-pyrrolo [1,2-a]quinoxalin]-2-ones has been synthesized by simple, highly efficient and environmentally friendly method in excellent yields under catalyst-free conditions using ethanol as a green solvent. A simple filtration of the reaction mixture and subsequent drying affords analytically pure products. The synthesized derivatives were evaluated for their antiproliferative activity against five different human cancer cell lines, among the congeners compound 3n showed significant cytotoxicity against the human prostate cancer (DU-145). Flow cytometric analysis revealed that this compound induces cell cycle arrest in the G0/G1 phase and Western blot analysis suggested that reduction in Cdk4 expression level leads to apoptotic cell death. This was further confirmed by mitochondrial membrane potential ((Delta Psi m), Annexin V-FITC assay and docking experiments. Furthermore, it was observed that there is an increase in expression levels of cyclin dependent kinase inhibitors like Cip1/p21 and Kip1/p27. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.046
• 作为产物：
  描述：

  靛红 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(1,3-苯并二氧代l-5-甲基)-1H-吲哚-2,3-二酮
  参考文献：
  名称：

  发现XEN907，它是Na V 1.7的螺内吲哚阻滞剂，可用于治疗疼痛

  摘要：

  从通过高通量筛选活动确定的羟吲哚2a开始，开发了一系列Na V 1.7阻滞剂。在消除了不良的结构特征之后，对羟吲哚C-3和N-1取代基进行了初步优化，得到了简化的类似物9b，与原始HTS命中相比，该类似物的目标效能提高了10倍。脚手架的加固策略随后导致了XEN907的发现，XEN907是一种新型螺氧吲哚Na V 1.7阻滞剂。这种先导化合物的效能又提高了10倍，代表了进一步优化工作的有希望的结构。

  DOI：

  10.1016/j.bmcl.2011.04.088

文献信息

• Oxindole compounds and their uses as therapeutic agents
  申请人：Chafeev Mikhail

  公开号：US20070105820A1

  公开（公告）日：2007-05-10

  This invention is directed to oxindole compounds that are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. Pharmaceutical compositions comprising the compounds and methods of using the compounds are also disclosed.

  本发明涉及氧化吲哚化合物，其对钠通道介导的疾病或病状，如疼痛的治疗和/或预防有用。还公开了包含该化合物的制药组合物和使用该化合物的方法。
• OXINDOLE COMPOUNDS AND THEIR USES AS THERAPEUTIC AGENTS
  申请人：XENON PHARMACEUTICALS INC.

  公开号：EP1877378A2

  公开（公告）日：2008-01-16
• [EN] OXINDOLE COMPOUNDS AND THEIR USES AS THERAPEUTIC AGENTS<br/>[FR] COMPOSES D'OXINDOLE ET LEURS UTILISATIONS COMME AGENTS THERAPEUTIQUES
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2006113864A2

  公开（公告）日：2006-10-26

  [EN] This invention is directed to oxindole compounds that are useful for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain. Pharmaceutical compositions comprising the compounds and methods of using the compounds are also disclosed.
  [FR] L'invention concerne des composés d'oxindole utilisés pour le traitement et/ou la prévention de maladies ou de pathologies induites par le canal de sodium, notamment les douleurs. L'invention concerne également des compositions pharmaceutiques comprenant les composés et des procédés d'utilisation des composés.
• [EN] USE OF OXINDOLE COMPOUNDS AS THERAPEUTIC AGENTS<br/>[FR] UTILISATION DE COMPOSÉS OXINDOLE COMME AGENTS THÉRAPEUTIQUES
  申请人：XENON PHARMACEUTICALS INC

  公开号：WO2008046083A2

  公开（公告）日：2008-04-17

  [EN] This invention is directed to methods of using oxindole compounds for the treatment and/or prevention of diseases or conditions such as hypercholesterolemia, benign prostatic hyperplasia, pruritis and cancer.
  [FR] L'invention concerne des procédés d'utilisation de composés oxindole destinés au traitement et/ou à la prévention de maladies ou de pathologies telles que l'hypercholestérolémie, l'hyperplasie prostatique bénigne, le prurit et le cancer.
• Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain
  作者：Sultan Chowdhury、Mikhail Chafeev、Shifeng Liu、Jianyu Sun、Vandna Raina、Ray Chui、Wendy Young、Rainbow Kwan、Jianmin Fu、Jay A. Cadieux

  DOI：10.1016/j.bmcl.2011.04.088

  日期：2011.6

  series of NaV1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold rigidification strategy then led to the discovery of XEN907, a novel spirooxindole NaV1.7 blocker. This

  从通过高通量筛选活动确定的羟吲哚2a开始，开发了一系列Na V 1.7阻滞剂。在消除了不良的结构特征之后，对羟吲哚C-3和N-1取代基进行了初步优化，得到了简化的类似物9b，与原始HTS命中相比，该类似物的目标效能提高了10倍。脚手架的加固策略随后导致了XEN907的发现，XEN907是一种新型螺氧吲哚Na V 1.7阻滞剂。这种先导化合物的效能又提高了10倍，代表了进一步优化工作的有希望的结构。