5,6-Dichloroindirubin | 667463-72-1

• 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: 5,6-Dichloroindirubin
• 英文别名: (3Z)-5,6-dichloro-3-(3-oxo-1H-indol-2-ylidene)-1H-indol-2-one
• CAS: 667463-72-1
• 化学式: C₁₆H₈Cl₂N₂O₂
• 分子量: 331.158
• InChiKey: MYUCRYLGBXDIEB-YPKPFQOOSA-N

物化性质

• 沸点：
  536.7±50.0 °C(Predicted)
• 密度：
  1.584±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.97
• 重原子数：
  22.0
• 可旋转键数：
  0.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.2
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5,6-Dichloroindirubin 在 吡啶 、 盐酸羟胺 作用下， 生成 5,6-Dichloroindirubin-3'-oxime
  参考文献：
  名称：

  首个 GPX4 和 CDK 双重抑制剂的设计、合成和生物学评价

  摘要：

  铁死亡和其他死亡方式的共存在癌症的治疗中具有很大的优势。鉴于 ML162 （GPX4 抑制剂） 与靛玉红-3′-肟 （IO） （CDK 抑制剂） 联合使用的协同抗癌作用，设计并合成了一系列谷胱甘肽过氧化物酶 4 （GPX4） 和细胞周期蛋白依赖性激酶 （CDK） 双重抑制剂。化合物 B9 对所有四种细胞系均表现出最高的潜在细胞毒活性，并且对 GPX4 表现出优异的抑制活性 （IC50 = 542.5 ± 0.9 nM） 和对 CDK 4/6 的选择性抑制 （IC50 = 191.2 ± 8.7、68.1 ± 1.4 nM）。机制研究表明，B9 可同时诱导 MDA-MB-231 细胞和 HCT-116 细胞的铁死亡和 G1 期细胞阻滞。与 ML162 和 IO 相比，B9 在体内表现出更强的癌细胞生长抑制作用。这些结果证明，开发有效的 GPX4/CDK 双重抑制剂是一种很有前途的恶性癌症治疗策略。

  DOI：

  10.1021/acs.jmedchem.3c01890
• 作为产物：
  描述：

  N-(α-Oximino-acetyl)-3.4-dichlor-anilin 在 硫酸 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 反应 3.25h， 生成 5,6-Dichloroindirubin
  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

• PHARMACEUTICAL COMPOSITION CONTAINING INDIRUBIN DERIVATIVE AS ACTIVE INGREDIENT
  申请人：CK Biotechnology Co.

  公开号：EP3613419A1

  公开（公告）日：2020-02-26

  A composition for promoting longitudinal bone growth, according to the present invention, promotes the proliferation of the chondrocytes and the differentiation of the osteoblasts and has effects of simultaneously increasing longitudinal bone length and thickness (bone density), and thus has an advantage of being widely prescribable to various age groups, thereby being usable as a pharmaceutical composition for promoting the growth of longitudinal bone length and thickness. An indirubin derivative according to the present invention has prevention or treatment effects through oral administration and has an excellent competitive price unlike conventional hormone-based therapeutic agents. In addition, unlike conventional therapeutic agents, the pharmaceutical composition for preventing or treating bone diseases of the present invention is a stable compound, which is known to be substantially noncytotoxic to the human body, and is a material of which adverse effects have not been identified and which has excellent treatment effects for bone diseases and osteogenesis imperfecta.

  根据本发明，一种促进骨纵向生长的组合物可促进软骨细胞的增殖和成骨细胞的分化，并具有同时增加骨纵向长度和厚度（骨密度）的效果，因此具有可广泛用于不同年龄组的优点，从而可用作促进骨纵向长度和厚度生长的药物组合物。根据本发明的靛蓝红素衍生物通过口服具有预防或治疗效果，并且与传统的激素类治疗剂不同，具有极好的价格竞争力。此外，与传统治疗剂不同的是，本发明用于预防或治疗骨病的药物组合物是一种稳定的化合物，已知对人体基本无细胞毒性，是一种尚未发现不良反应的材料，对骨病和成骨不全症具有良好的治疗效果。
• PHARMACEUTICAL COMPOSITION COMPRISING INDIRUBIN DERIVATIVE AS ACTIVE INGREDIENT
  申请人：CK Biotech

  公开号：EP3818980A1

  公开（公告）日：2021-05-12

  The present disclosure relates to a composition for preventing or treating wound. The composition according to the present disclosure contains, as an active ingredient, an indirubin derivative alone or one or more selected from a group consisting of an indirubin derivative, an Euodia sutchuenensis Dode extract, methyl vanillate, hesperidin and quercitrin, and thus can be used as a pharmaceutical composition capable of promoting wound healing and reducing scarring not only in a normal state but also in a diabetic state. Furthermore, since the composition exhibits excellent effects in healing diabetic wound as well as general wound, it can be usefully used as a pharmaceutical composition, cosmetic composition or food composition for alleviating, preventing or treating general wound or diabetic wound, or as a veterinary composition for treating diabetic wound.

  本公开涉及一种用于预防或治疗伤口的组合物。根据本公开的组合物，作为活性成分，单独含有一种靛红素衍生物或一种或多种选自靛红素衍生物、Euodia sutchuenensis Dode 提取物、香草酸甲酯、橙皮甙和槲皮素的组，因此可用作药物组合物，不仅在正常状态下，而且在糖尿病状态下，都能促进伤口愈合和减少疤痕。此外，由于该组合物在愈合糖尿病伤口和一般伤口方面都表现出卓越的效果，因此它可作为药物组合物、化妆品组合物或食品组合物，用于减轻、预防或治疗一般伤口或糖尿病伤口，或作为兽用组合物用于治疗糖尿病伤口。
• Indirubin derivatives, and uses thereof
  申请人：CITY OF HOPE

  公开号：US10435367B2

  公开（公告）日：2019-10-08

  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。
• Composition for preventing hair loss or promoting hair growth
  申请人：CK BIOTECH

  公开号：US11154566B2

  公开（公告）日：2021-10-26

  The present invention is about composition for preventing hair loss or promoting hair growth comprising indirubin derivatives; and one or more selected from the group consisting of Euodia daniellii extract, Persicaria hydropiper extract, Hovenia dulcis extract, methyl vanillate, hesperidin and quercitrin; as an active ingredient. In addition, one or more selected from the group consisting of Euodia daniellii extract, Persicaria hydropiper extract, Hovenia dulcis extract, methyl vanillate, hesperidin and quercitrin of the present invention is a natural-derived composition with little toxicity to cells. Indirubin derivatives are stable compounds that have been found to have little toxicity to the human body, and therefore, when used in a mixture thereof, there are advantages in that they do not exhibit adverse effects on the human body, unlike conventional steroid drugs.

  本发明涉及用于防止脱发或促进毛发生长的组合物，该组合物包含靛红衍生物；以及选自Euodia daniellii提取物、Persicaria hydropiper提取物、Hovenia dulcis提取物、香草酸甲酯、橙皮甙和槲皮甙组成的组中的一种或多种作为活性成分。 此外，本发明的一种或多种选自 Euodia daniellii 提取物、Persicaria hydropiper 提取物、Hovenia dulcis 提取物、香草酸甲酯、橙皮甙和槲皮甙的天然成分对细胞毒性很小。靛红衍生物是一种稳定的化合物，对人体的毒性很小，因此，与传统的类固醇药物不同，在使用它们的混合物时，不会对人体产生不良影响。
• COMPOSITION FOR PREVENTING HAIR LOSS OR PROMOTING HAIR GROWTH
  申请人：CK BIOTECH

  公开号：US20200179425A1

  公开（公告）日：2020-06-11

  The present invention is about composition for preventing hair loss or promoting hair growth comprising indirubin derivatives; and one or more selected from the group consisting of Euodia daniellii extract, Persicaria hydropiper extract, Hovenia dulcis extract, methyl vanillate, hesperidin and quercitrin; as an active ingredient. In addition, one or more selected from the group consisting of Euodia daniellii extract, Persicaria hydropiper extract, Hovenia dulcis extract, methyl vanillate, hesperidin and quercitrin of the present invention is a natural-derived composition with little toxicity to cells. Indirubin derivatives are stable compounds that have been found to have little toxicity to the human body, and therefore, when used in a mixture thereof, there are advantages in that they do not exhibit adverse effects on the human body, unlike conventional steroid drugs.