6-amino-N-[1-(2,6-dichlorophenyl)methyl]-1H-indole | 314752-14-2

• 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-amino-N-[1-(2,6-dichlorophenyl)methyl]-1H-indole
• 英文别名: 1-[(2,6-dichlorophenyl)methyl]indol-6-amine
• CAS: 314752-14-2
• 化学式: C₁₅H₁₂Cl₂N₂
• 分子量: 291.18
• InChiKey: VIZSCCAJFGMWPG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  31
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-amino-N-[1-(2,6-dichlorophenyl)methyl]-1H-indole 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-Amino-2-[(S)-2-{3-[1-(2,6-dichloro-benzyl)-3-pyrrolidin-1-ylmethyl-1H-indol-6-yl]-ureido}-3-(3,4-difluoro-phenyl)-propionylamino]-N-furan-2-ylmethyl-butyramide
  参考文献：
  名称：

  High-affinity thrombin receptor (PAR-1) ligands: a new generation of indole-based peptide mimetic antagonists with a basic amine at the C-terminus

  摘要：

  A new generation of indole-based peptide mimetics, bearing a basic amine at the C-terminus, was developed by the agency of two complementary, multistep, trityl resin-based approaches. Thus, we obtained several high-affinity thrombin receptor (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR-1 with excellent affinity IC50 = 25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH2 (TRAP-6) and alpha-thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00325-1
• 作为产物：
  描述：

  2,6-二氯苄基溴 在 三氯化铁 、 甲烷 、 caesium carbonate 、 偏二甲肼 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 6-amino-N-[1-(2,6-dichlorophenyl)methyl]-1H-indole
  参考文献：
  名称：

  High-affinity thrombin receptor (PAR-1) ligands: a new generation of indole-based peptide mimetic antagonists with a basic amine at the C-terminus

  摘要：

  A new generation of indole-based peptide mimetics, bearing a basic amine at the C-terminus, was developed by the agency of two complementary, multistep, trityl resin-based approaches. Thus, we obtained several high-affinity thrombin receptor (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR-1 with excellent affinity IC50 = 25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH2 (TRAP-6) and alpha-thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00325-1

文献信息

• Novel indole peptidomimetics as thrombin receptor antagonists
  申请人：——

  公开号：US20030224999A1

  公开（公告）日：2003-12-04

  The invention is directed to novel indole peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted indole peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed.

  该发明涉及一种新型吲哌啶肽类模拟化合物，可用作治疗与血栓形成、再狭窄、高血压、心力衰竭、心律失常、炎症、心绞痛、中风、动脉粥样硬化、缺血情况、血管生成相关疾病、癌症和神经退行性疾病相关的疾病的凝血酶受体拮抗剂。还公开了包含本发明替代吲哌啶肽类模拟化合物的药物组合物以及治疗由凝血酶受体介导的疾病的方法。
• Process for Production of (1,3-Disubstituted Indolyl)-Urea Derivatives, Intermediates Therefor, and Process for Production of the Intermediates
  申请人：Kabeya Mototsugu

  公开号：US20090012263A1

  公开（公告）日：2009-01-08

  A process for the production of (1,3-disubstituted indolyl) urea derivatives represented by the general formula (1), characterized by reacting a 1-substituted-aminoindole derivative with a phenyl halocarbonate to form a carbamate derivative, subjecting the carbamate derivative to Mannich reaction with a secondary amine and formaldehyde to form a 3-aminomethylindole derivative represented by the general formula (6), and then reacting the derivative (6) with a peptide derivative; indole derivatives represented by the general formula (6) which are intermediates for the above process; and a process for the production of the indole derivatives.

  一种制备（1,3-二取代吲哚基）脲衍生物的过程，其通式为（1），其特征在于将1-取代氨基吲哚衍生物与苯基卤代碳酸酯反应形成氨基甲酸酯衍生物，将氨基甲酸酯衍生物通过曼尼希反应与二级胺和甲醛反应形成通式（6）所表示的3-氨甲基吲哚衍生物，然后将衍生物（6）与肽衍生物反应；通式（6）所表示的吲哚衍生物是上述过程的中间体；以及制备吲哚衍生物的过程。
• PROCESS FOR PRODUCTION OF (1,3-DISUBSTITUTED INDOLYL)- UREA DERIVATIVES, INTERMEDIATES THEREFOR, AND PROCESS FOR PRODUCTION OF THE INTERMEDIATES
  申请人：Kowa Company. Ltd.

  公开号：EP1806355A1

  公开（公告）日：2007-07-11

  A process for the production of (1,3-disubstituted indolyl) urea derivatives represented by the general formula (1), characterized by reacting a 1-substituted-aminoindole derivative with a phenyl halocarbonate to form a carbamate derivative, subjecting the carbamate derivative to Mannich reaction with a secondary amine and formaldehyde to form a 3-aminomethylindole derivative represented by the general formula (6), and then reacting the derivative (6) with a peptide derivative; indole derivatives represented by the general formula (6) which are intermediates for the above process; and a process for the production of the indole derivatives.

  一种生产通式(1)代表的(1,3-二取代吲哚基)脲衍生物的工艺，其特征在于将1-取代-氨基吲哚衍生物与卤代碳酸苯酯反应生成氨基甲酸酯衍生物，将氨基甲酸酯衍生物与仲胺和甲醛进行曼尼希反应生成通式(6)代表的3-氨基甲基吲哚衍生物，然后将衍生物(6)与肽衍生物反应；通式（6）代表的吲哚衍生物，它是上述工艺的中间体；以及生产吲哚衍生物的工艺。
• Thrombin receptor (PAR-1) antagonists. Solid-Phase synthesis of indole-Based peptide mimetics by anchoring to a secondary amide
  作者：Han-Cheng Zhang、David F McComsey、Kimberly B White、Michael F Addo、Patricia Andrade-Gordon、Claudia K Derian、Donna Oksenberg、Bruce E Maryanoff

  DOI：10.1016/s0960-894x(01)00378-x

  日期：2001.8

  A novel, 10-step, solid-phase method, based on a secondary amide linker, was developed to construct a diverse library of indole-based SFLLR peptide mimetics as thrombin receptor (protease-activated receptor 1, PAR-I) antagonists. The key steps include stepwise reductive alkylation, urea formation, and Mannich reaction. Screening of the library led to a quick development of the SAR and the significant improvement of PAR-1 activity. (C) 2001 Elsevier Science Ltd. All rights reserved.
• High-affinity thrombin receptor (PAR-1) ligands: a new generation of indole-based peptide mimetic antagonists with a basic amine at the C-terminus
  作者：Han-Cheng Zhang、Kimberly B. White、David F. McComsey、Michael F. Addo、Patricia Andrade-Gordon、Claudia K. Derian、Donna Oksenberg、Bruce E. Maryanoff

  DOI：10.1016/s0960-894x(03)00325-1

  日期：2003.7

  A new generation of indole-based peptide mimetics, bearing a basic amine at the C-terminus, was developed by the agency of two complementary, multistep, trityl resin-based approaches. Thus, we obtained several high-affinity thrombin receptor (PAR-1) ligands, such as 32 and 34. Compounds 32 and 34 were found to bind to PAR-1 with excellent affinity IC50 = 25 and 35 nM, respectively) and to effectively block platelet aggregation induced by SFLLRN-NH2 (TRAP-6) and alpha-thrombin. (C) 2003 Elsevier Science Ltd. All rights reserved.