6-bromo-3-[3-(hydroxyamino)indol-2-ylidene]-1-methylindol-2-one | 667463-95-8

• 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: 6-bromo-3-[3-(hydroxyamino)indol-2-ylidene]-1-methylindol-2-one
• 英文别名: 6-Bromo-1-methylindirubin-3'-oxime；methyl-6BIO；Me6BIO；MeBIO
• CAS: 667463-95-8
• 化学式: C₁₇H₁₂BrN₃O₂
• 分子量: 370.205
• InChiKey: JUKQKURGZYNHFN-NVVUQHMZSA-N

物化性质

• 溶解度：
  在 DMSO 中溶解度为 10 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  23.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  64.93
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 6-bromo-3-[3-(hydroxyamino)indol-2-ylidene]-1-methylindol-2-one 在 吡啶 作用下， 反应 0.5h， 生成 (2'Z,3'E)-6-bromo-1-methylindirubin-3'-acetoxime
  参考文献：
  名称：

  Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases

  摘要：

  Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.

  DOI：

  10.1021/jm031016d
• 作为产物：
  描述：

  N-(3-bromophenyl)-2-hydroxyiminacetamide 在 吡啶 、 硫酸 、 盐酸羟胺 、 sodium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 6.75h， 生成 6-bromo-3-[3-(hydroxyamino)indol-2-ylidene]-1-methylindol-2-one
  参考文献：
  名称：

  Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases

  摘要：

  Pharmacological inhibitors of glycogen synthase kinase-3 (GSK-3) and cyclin-dependent kinases have a promising potential for applications against several neurodegenerative diseases such as Alzheimer's disease. Indirubins, a family of bis-indoles isolated from various natural sources, are potent inhibitors of several kinases, including GSK-3. Using the cocrystal structures of various indirubins with GSK-3beta, CDK2 and CDK5/p25, we have modeled the binding of indirubins within the ATP-binding pocket of these kinases. This modeling approach provided some insight into the molecular basis of indirubins' action and selectivity and allowed us to forecast some improvements of this family of bis-indoles as kinase inhibitors. Predicted molecules, including 6-substituted and 5,6-disubstituted indirubins, were synthesized and evaluated as CDK and GSK-3 inhibitors. Control, kinase-inactive indirubins were obtained by introduction of a methyl substitution on N1.

  DOI：

  10.1021/jm031016d

文献信息

• ARYL HYDROCARBON RECEPTOR MODULATOR
  申请人：Shenzhen Immunova Pharmaceutical Co., Ltd.

  公开号：EP3564239A1

  公开（公告）日：2019-11-06

  The invention discloses an aryl hydrocarbon receptor modulators of formula (I), and pharmaceutically acceptable salts thereof, R' is H, CN, CH2(OH)R0, CmH2m+1, CnH2n-1, CnH2n-3, two Ra is independently H, or two Ra together form =O or =N-W3-R1; A is a C6 to C10 aromatic ring, or a C2 to C10 heteroaromatic ring containing 1 to 5 heteroatom selected from N, O and S, or 4 to 7 membered non-aromatic heterocyclic ring containing 1 to 3 heteroatom selected from N, O and S and C=N, which are with no substituent or substituted by 1 or 3 R; Q is R, or a C6 to C10 aromatic ring or a C2 to C10 heteroaromatic ring containing 1 to 5 heteroatom selected from N, O and S, which are with no substituent or substituted by 1 or 3 R; R is Rc connected with C or RN connected with N. Compounds of this invention of formula (I) can modulate activity of AhR for inhibiting growth of cancer cell and inhibiting migration and invasion of tumour cell.

  本发明公开了式 (I) 的芳基烃受体调节剂及其药学上可接受的盐类、 R' 是 H、CN、CH2(OH)R0、CmH2m+1、CnH2n-1、CnH2n-3、 两个 Ra 独立地是 H，或两个 Ra 一起形成 =O 或 =N-W3-R1 ；A 是 C6 至 C10 芳环，或含有 1 至 5 个选自 N、O 和 S 的杂原子的 C2 至 C10 杂芳香环，或含有 1 至 3 个选自 N、O 和 S 的杂原子的 4 至 7 个构元的非芳香杂环，以及 C=N，其中不含取代基或被 1 或 3 个 R 取代；Q 是 R，或 C6 至 C10 芳环，或 C2 至 C10 杂芳环，其中含有 1 至 5 个选自 N、O 和 S 的杂原子，它们不含取代基或被 1 或 3 个 R 取代；R 是与 C 相连的 Rc 或与 N 相连的 RN。本发明的式(I)化合物可以调节 AhR 的活性，从而抑制癌细胞的生长，抑制肿瘤细胞的迁移和侵袭。
• Pharmaceutical composition comprising refined indigo naturalis extract and the use thereof
  申请人：Galderma S.A.

  公开号：US10232006B2

  公开（公告）日：2019-03-19

  A refined Indigo Naturalis extract or Indigo-producing plant extract containing at least 65% (w/w) an indirubin derivative based on total weight of active ingredients is described. Also described are a pharmaceutical composition containing the refined extract, and the use of the pharmaceutical composition for treating or alleviating a disease or condition.

  本研究描述了一种精制的天然靛蓝提取物或靛蓝生产植物提取物，其活性成分总重量中至少含有 65%（重量比）的靛蓝素衍生物。 此外，还介绍了一种含有该精制提取物的药物组合物，以及使用该药物组合物治疗或缓解疾病或病症的方法。
• Pharmaceutical composition comprising refined Indigo naturalis extracts and the use thereof
  申请人：Galderma S.A.

  公开号：US10555985B2

  公开（公告）日：2020-02-11

  A refined Indigo Naturalis extract or Indigo-producing plant extract containing at least 65% (w/w) an indirubin derivative based on total weight of active ingredients is described. Also described are a pharmaceutical composition containing the refined extract, and the use of the pharmaceutical composition for treating or alleviating a disease or condition.

  本研究描述了一种精制的天然靛蓝提取物或靛蓝生产植物提取物，其活性成分总重量中至少含有 65%（重量比）的靛蓝素衍生物。此外，还介绍了一种含有该精制提取物的药物组合物，以及使用该药物组合物治疗或缓解疾病或病症的方法。
• Pharmaceutical composition comprising refined indigo naturalis extracts and the use thereof
  申请人：Galderma S.A.

  公开号：US11116811B2

  公开（公告）日：2021-09-14

  A refined Indigo Naturalis extract or Indigo-producing plant extract containing at least 65% (w/w) an indirubin derivative based on total weight of active ingredients is described. Also described are a pharmaceutical composition containing the refined extract, and the use of the pharmaceutical composition for treating or alleviating a disease or condition.

  本研究描述了一种精制的天然靛蓝提取物或靛蓝生产植物提取物，其活性成分总重量中至少含有 65%（重量比）的靛蓝素衍生物。此外，还介绍了一种含有该精制提取物的药物组合物，以及使用该药物组合物治疗或缓解疾病或病症的方法。
• Indirubin derivatives, and uses thereof
  申请人：CITY OF HOPE

  公开号：US11524937B2

  公开（公告）日：2022-12-13

  Indirubin is the major active anti-tumor component of a traditional Chinese herbal medicine used for treatment of chronic myelogenous leukemia (CML). Indirubin derivatives (IRDs) potently reduce the viabilities of various cancer cells and affect kinase activities. IRDs disclosed herein provide new therapeutics for cancer and conditions regulated by the kinase activities.

  靛红素是一种用于治疗慢性骨髓性白血病（CML）的传统中药的主要抗肿瘤活性成分。靛红衍生物（IRDs）能有效降低各种癌细胞的存活率并影响激酶活性。本文公开的 IRDs 为癌症和受激酶活性调节的疾病提供了新的治疗方法。