6-iodo-5-methoxy-1-methyl-1H-indole | 1034895-54-9

• 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-iodo-5-methoxy-1-methyl-1H-indole
• 英文别名: 6-Iodo-5-methoxy-1-methylindole
• CAS: 1034895-54-9
• 化学式: C₁₀H₁₀INO
• 分子量: 287.1
• InChiKey: ZSKXFFDNKPLOQR-UHFFFAOYSA-N

物化性质

• 沸点：
  364.7±27.0 °C(Predicted)
• 密度：
  1.69±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  14.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-iodo-5-methoxy-1-methyl-1H-indole 、 草酰氯单乙酯 以 乙醚 为溶剂， 生成 C₁₄H₁₄INO₄
  参考文献：
  名称：

  From a Natural Product Lead to the Identification of Potent and Selective Benzofuran-3-yl-(indol-3-yl)maleimides as Glycogen Synthase Kinase 3β Inhibitors That Suppress Proliferation and Survival of Pancreatic Cancer Cells

  摘要：

  Recent studies have demonstrated that glycogen synthase kinase 3 beta (GSK-3 beta) is overexpressed in human colon and pancreatic carcinomas, contributing to cancer cell proliferation and survival. Here, we report the design, synthesis, and biological evaluation of benzofuran-3-yl-(indol-3-yl)maleimides, potent GSK-3 beta inhibitors. Some of these compounds show picomolar inhibitory activity toward GSK-3 beta and an enhanced selectivity against cycl in-dependent kinase 2 (CDK-2). Selected GSK-3 beta inhibitors were tested in the pancreatic cancer cell lines MiaPaCa-2, BXPC-3, and HupT3. We determined that some of these compounds, namely compounds 5, 6, 11, 20, and 26, demonstrate antiproliferative activity against some or all of the pancreatic cancer cells at low micromolar to nanomolar concentrations. We found that the treatment of pancreatic cancer cells with GSK-3 beta inhibitors 5 and 26 resulted in suppression of GSK-3 beta activity and a distinct decrease of the X-linked inhibitor of apoptosis (XIAP) expression, leading to significant apoptosis. The present data suggest a possible role for GSK-3 beta inhibitors in cancer therapy, in addition to their more prominent applications in CNS disorders.

  DOI：

  10.1021/jm801317h
• 作为产物：
  描述：

  1-(6-iodo-5-methoxyindolin-1-yl)ethan-1-one 在 salcomine 、 sodium hydride 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.17h， 生成 6-iodo-5-methoxy-1-methyl-1H-indole
  参考文献：
  名称：

  以碳酸二甲酯为甲基源，通过碱基控制的 C-H 活化级联，Pd 催化 ipso，邻位取代碘芳烃的间二甲基化

  摘要：

  甲基可以对有机分子的药理特性产生深远的影响。因此，开发甲基化方法和甲基化试剂在药物化学中是必不可少的。我们报告了使用碳酸二甲酯作为甲基源的邻位取代碘芳烃的钯催化二甲基化反应。在K的存在2 CO 3作为碱，iodoarenes是在二甲基化本位以及-元的碘基团，它代表一种新颖的策略的位上的元-C-H甲基化。以 KOAc 为碱，随后的氧化 C(sp 3 )–H/C(sp 3)–H 耦合发生；在这种情况下，整体转化实现了三重 C-H 激活，形成三个新的 C-C 键。这些反应可以方便地获得 2,6-二甲基苯酚、2,3-二氢苯并呋喃和茚满，它们是普遍存在的结构基序和生物和药理活性化合物的基本合成中间体。

  DOI：

  10.1021/jacs.0c13057

文献信息

• Pd-catalyzed cross-electrophile Coupling/C–H alkylation reaction enabled by a mediator generated <i>via</i> C(sp³)–H activation
  作者：Zhuo Wu、Hang Jiang、Yanghui Zhang

  DOI：10.1039/d1sc01731d

  日期：——

  Transition-metal-catalyzed cross-electrophile C(sp2)–(sp3) coupling and C–H alkylation reactions represent two efficient methods for the incorporation of an alkyl group into aromatic rings. Herein, we report a Pd-catalyzed cascade cross-electrophile coupling and C–H alkylation reaction of 2-iodo-alkoxylarenes with alkyl chlorides. Methoxy and benzyloxy groups, which are ubiquitous functional groups

  过渡金属催化的交叉亲电试剂C（sp 2）–（sp 3）偶联和C–H烷基化反应代表了将烷基结合到芳环中的两种有效方法。在这里，我们报道了2-碘-烷氧基芳烃与烷基氯的钯催化级联交叉亲电子偶联和CH烷基化反应。甲氧基和苄氧基基团是普遍存在的官能团和常见的保护基团，被用作通过一级或二级C（sp 3）–H活化的关键介质。该反应为合成烷基化的苯酚衍生物提供了一种新颖而便捷的途径，烷基化的苯酚衍生物广泛存在于生物活性化合物和有机功能材料中。
• Benzofuran-3-yl(indol-3-yl) Maleimides as Potent GSK3 Inhibitors
  申请人：KOZIKOWSKI Alan P.

  公开号：US20100004308A1

  公开（公告）日：2010-01-07

  Compounds of formula: and pharmaceutically acceptable salts, esters and solvates thereof, where variables are defined in the specification, useful generally as inhibitors of protein kinases and particularly useful for inhibition of GSK-3. Pharmaceutically compositions and medicaments containing a compound of the invention are provided. The invention provides methods of treatment of protein kinase-related disease, disorders or conditions. The invention provides methods of treatment of GSK-3-related diseases, disorders or conditions. More specifically, methods of treatment of bipolar disorder, including mania, schizophrenia, stroke, epilepsy, motor neuron disease, cranial or spinal trauma, neurodegenerative disorders, including multiple sclerosis (MS), Alzheimer's disease, Fragile X syndrome, autism, Huntington's disease, Parkinson's disease, amylotrophic lateral sclerosis (ALS), AIDS-associated dementia, diabetes, particularly type II diabetes, cardiomycete hypertrophy, reperfusion/ischemia, cancer, particularly colorectal cancer, pancreatic cancer, allergies and/or asthma and hair loss or baldness.

  该化合物的公式：以及其药学上可接受的盐、酯和溶剂化物，其中变量在说明书中定义，通常用作蛋白激酶抑制剂，特别是用于抑制GSK-3。提供了含有发明化合物的药学组合物和药物。本发明提供了治疗蛋白激酶相关疾病、紊乱或病况的方法。本发明提供了治疗GSK-3相关疾病、紊乱或病况的方法。更具体地，本发明提供了治疗双相情感障碍、包括躁狂、精神分裂症、中风、癫痫、运动神经元疾病、头部或脊柱创伤、神经退行性疾病、包括多发性硬化症（MS）、阿尔茨海默病、脆性X综合征、自闭症、亨廷顿病、帕金森病、肌萎缩性脊髓侧索硬化症（ALS）、艾滋病相关痴呆、糖尿病，特别是II型糖尿病、心肌肥厚、复灌/缺血、癌症，特别是结肠癌、胰腺癌、过敏和/或哮喘以及脱发或秃发的方法。
• WO2008/77138
  申请人：——

  公开号：——

  公开（公告）日：——
• 3-BENZOFURANYL-4-INDOLYL-MALEIMIDES AS POTENT GSK-3 INHIBITORS FOR NEURODEGENERATIVE DISORDERS
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2125683B1

  公开（公告）日：2013-10-23
• US8207216B2
  申请人：——

  公开号：US8207216B2

  公开（公告）日：2012-06-26