(benzofuran-3-yl)-oxo-acetic acid ethyl ester | 143883-38-9

• 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: (benzofuran-3-yl)-oxo-acetic acid ethyl ester
• 英文别名: ethyl-α-oxo-3-benzofuran acetate；Ethyl 2-(benzofuran-3-yl)-2-oxoacetate；ethyl 2-(1-benzofuran-3-yl)-2-oxoacetate
• CAS: 143883-38-9
• 化学式: C₁₂H₁₀O₄
• 分子量: 218.209
• InChiKey: WHUYLQWBMYFFLT-UHFFFAOYSA-N

物化性质

• 沸点：
  324.9±15.0 °C(Predicted)
• 密度：
  1.251±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (benzofuran-3-yl)-oxo-acetic acid ethyl ester 、 1-甲基吲哚-3-乙酰胺 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 以44%的产率得到3-(benzofuran-3-yl)-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione
  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
• 作为产物：
  描述：

  在 对甲苯磺酸 作用下， 以 乙腈 为溶剂， 反应 8.0h， 以82%的产率得到(benzofuran-3-yl)-oxo-acetic acid ethyl ester
  参考文献：
  名称：

  一种苯并呋喃-3-氧代羧酸酯类化合物的合成方法

  摘要：

  本发明公开了一种苯并呋喃‑3‑氧代羧酸酯类化合物的合成方法，该方法是将共轭烯基脒类化合物在

  公开号：

  CN113214199B

文献信息

• Rhodium-catalyzed enantioselective 1,2-addition of arylboronic acids to heteroaryl α-ketoesters for synthesis of heteroaromatic α-hydroxy esters
  作者：Hui Wang、Ting-Shun Zhu、Ming-Hua Xu

  DOI：10.1039/c2ob26316e

  日期：——

  The first example of catalytic asymmetric 1,2-addition of arylboronic acids to heteroaryl α-ketoesters has been developed for the highly efficient and enantioselective synthesis of quaternary carbon-containing heteroaromatic α-hydroxy esters. The reaction works well with a variety of α-ketoesters including 3-indoleglyoxylates, 3-benzofuranglyoxylates and 3-benzothiopheneglyoxylates under very mild conditions, affording the corresponding products in moderate to good yields with high enantiomeric excesses (up to 97%).

  第一例催化不对称1,2-加成芳基硼酸到杂芳类α-酮酯的反应已经被开发，用于高效和选择性合成四次碳含量的杂芳类α-羟基酯。在非常温和的条件下，该反应对多种α-酮酯表现良好，包括3-吲哚乙二酸酯、3-苯并呋喃乙二酸酯和3-苯并噻吩乙二酸酯，产物的收率中等到良好，且具有高的对映体过量（高达97%）。
• 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。
• Benzofuran-3-yl(indol-3-yl) maleimides as potent GSK3 inhibitors
  申请人：The Board of Trustees of the University of Illinois

  公开号：US08207216B2

  公开（公告）日：2012-06-26

  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.

  此处提供的化合物公式为：和其药用可接受的盐、酯和溶剂化物，其中变量定义在说明书中，通常用作蛋白激酶抑制剂，特别适用于GSK-3的抑制。本发明提供了含有该化合物的药物组合物和药物。本发明提供了治疗蛋白激酶相关疾病、疾病或病况的方法。本发明提供了治疗GSK-3相关疾病、疾病或病况的方法。更具体地，包括躁狂症、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综合症、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2型糖尿病、心肌肥厚、再灌注/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治疗方法。
• Palladium-catalyzed C–C bond cleavage of <i>N</i>-cyclopropyl acylhydrazones
  作者：Hiroki Fujioka、Motohiro Yasui、Shohei Hamada、Kohei Fukumi、Norihiko Takeda、Yusuke Kobayashi、Takumi Furuta、Masafumi Ueda

  DOI：10.1039/d4ob00349g

  日期：2024.4.24

  Despite their utility as directing groups, the C–C bond cleavage of cyclopropanes utilizing hydrazones has not been explored. Herein, Pd-catalyzed C–C bond cleavage reaction of N-cyclopropyl acylhydrazones, followed by cycloisomerization to yield pyrazoles, has been developed. The protocol enables the synthesis of various α-pyrazole carbonyl compounds, which have a potential of biological activity. Control

  尽管它们可用作导向基团，但尚未探索利用腙对环丙烷进行 C-C 键断裂。在此，开发了 Pd 催化N-环丙基酰腙的 C-C 键断裂反应，然后进行环异构化生成吡唑。该方案能够合成各种具有潜在生物活性的α-吡唑羰基化合物。对照实验和 DFT 计算表明，稳定的 6 元螯合钯配合物发生 β-碳消除，生成共轭吖嗪作为后续环异构化的反应中间体。
• WO2008/77138
  申请人：——

  公开号：——

  公开（公告）日：——