5-cyclopropyl-1-methyl-1H-indole | 953812-05-0

• 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-cyclopropyl-1-methyl-1H-indole
• 英文别名: 5-cyclopropyl-1-methylindole
• CAS: 953812-05-0
• 化学式: C₁₂H₁₃N
• 分子量: 171.242
• InChiKey: ZAURROWVRKXXRG-UHFFFAOYSA-N

物化性质

• 沸点：
  313.1±11.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  4.9
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  5-cyclopropyl-1-methyl-1H-indole 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 生成 (3-benzofuran-3-yl)-4-(5-cyclopropyl-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：

  5-碘-1-甲基-1H-吲哚 在 四(三苯基膦)钯 lithium chloride 作用下， 以 1,4-二氧六环 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 5-cyclopropyl-1-methyl-1H-indole
  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。
• 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。
• Picolinamide Ligands: Nickel‐Catalyzed Reductive Cross‐Coupling of Aryl Bromides with Bromocyclopropane and Beyond
  作者：Dongyang Han、Jie Sun、Jian Jin

  DOI：10.1002/asia.202201132

  日期：2023.1.17

  The arylcyclopropane motif as the combination of aryl and cyclopropyl ring systems can be found in an increasing amount of approved and investigational drugs. Herein, we have developed a mild, efficient nickel-catalyzed reductive cross-coupling protocol, featuring a simple Ni(II) precatalyst, a novel picolinamide NN2 pincer ligand. Notably, the reaction is tolerant of a broad range of functionalities

  芳基环丙烷基序作为芳基和环丙基环系统的组合，可以在越来越多的批准和研究药物中找到。在此，我们开发了一种温和、高效的镍催化还原交叉偶联方案，其特点是一种简单的 Ni(II) 预催化剂，一种新型吡啶酰胺 NN 2钳形配体。值得注意的是，该反应对包括游离胺在内的广泛功能具有耐受性。
• Direct Suzuki‐Miyaura Coupling of Naphthalene‐1,8‐diaminato (dan)‐Substituted Cyclopropylboron Compounds
  作者：Mikinao Koishi、Kazuki Tomota、Masaaki Nakamoto、Hiroto Yoshida

  DOI：10.1002/adsc.202201141

  日期：2023.3.7

  describe the direct Suzuki-Miyaura coupling of dan-substituted, saturated organoboron compounds. Despite its Lewis acidity-diminished character of the boron center, cyclopropyl-B(dan) can be activated by t-BuOK to undergo transmetalation with a palladium complex. The increased s-character of the C−B(dan) bond as compared with other alkyl-B(dan) should be the key to the reaction.

  我们在此描述了丹取代的饱和有机硼化合物的直接 Suzuki-Miyaura 偶联。尽管硼中心具有路易斯酸度降低的特性，但环丙基-B(dan) 可以被t -BuOK 激活，与钯配合物进行金属转移。与其他烷基-B(dan)相比，C−B(dan)键的s-特征增加应该是反应的关键。
• Artificial self-sufficient cytochrome P450s
  申请人：University of Florida Research Foundation, Incorporated

  公开号：US10138205B2

  公开（公告）日：2018-11-27

  The disclosure relates to the field of fusion proteins. In some aspects, the invention relates to artificial fusion proteins comprising cytochrome P450 enzymes linked to reductase enzymes and uses thereof. In some aspects, the disclosure relates to compounds produced by artificial cytochrome P450 enzymes.

  本发明涉及融合蛋白领域。 在某些方面，本发明涉及由与还原酶连接的细胞色素 P450 酶组成的人工融合蛋白及其用途。 在某些方面，本发明涉及由人工细胞色素P450酶产生的化合物。