2-(7-methoxybenzofuran-3-yl)acetamide | 941576-01-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 2-(7-methoxybenzofuran-3-yl)acetamide
• 英文别名: 7-methoxy-benzofuran-3-acetamide；2-(7-Methoxy-1-benzofuran-3-yl)acetamide
• CAS: 941576-01-8
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: RFRSDKUNXWRIAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  65.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(7-methoxybenzofuran-3-yl)acetamide 、 (5-fluoro-6-iodo-1-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以52%的产率得到3-(5-fluoro-6-iodo-1-methyl-1H-indol-3-yl)-4-(7-methoxybenzofuran-3-yl)pyrrole-2,5-dione
  参考文献：
  名称：

  WO2008/77138

  摘要：

  公开号：
• 作为产物：
  描述：

  7-甲氧基-3(2H)-苯并呋喃酮 在 氨 作用下， 以 甲苯 为溶剂， 反应 72.0h， 生成 2-(7-methoxybenzofuran-3-yl)acetamide
  参考文献：
  名称：

  Structure-Based Design Leads to the Identification of Lithium Mimetics That Block Mania-like Effects in Rodents. Possible New GSK-3β Therapies for Bipolar Disorders

  摘要：

  More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3 beta inhibitors. The best ligand in this series (having a K-i value of 4.6 nM against GSK-3 beta) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3 beta inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.

  DOI：

  10.1021/ja068969w

文献信息

• 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。
• 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
  作者：Irina N. Gaisina、Franck Gallier、Andrei V. Ougolkov、Ki H. Kim、Toru Kurome、Songpo Guo、Denise Holzle、Doris N. Luchini、Sylvie Y. Blond、Daniel D. Billadeau、Alan P. Kozikowski

  DOI：10.1021/jm801317h

  日期：2009.4.9

  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.
• 3-BENZOFURANYL-4-INDOLYL MALEIMIDES AS POTENT GSK3 INHIBITORS FOR NEUROGENERATIVE DISORDERS
  申请人：The Board of Trustees of the University of Illinois

  公开号：EP2125683A1

  公开（公告）日：2009-12-02
• 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