2-(6-chloro-1H-indol-3-yl)-2-oxo-N-phenylacetamide | 1257651-86-7

• 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: 2-(6-chloro-1H-indol-3-yl)-2-oxo-N-phenylacetamide
• CAS: 1257651-86-7
• 化学式: C₁₆H₁₁ClN₂O₂
• 分子量: 298.729
• InChiKey: CTCGYBNNTCNHNN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(6-chloro-1H-indol-3-yl)-2-oxo-N-phenylacetamide 在 甲醇 、 sodium tetrahydroborate 、 三甲基氯硅烷 、 臭氧 、 sodium iodide 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 12.75h， 生成
  参考文献：
  名称：

  环的断裂和制造：一种制备 4-喹诺酮-3-羧酸酰胺和昂贵药物 Ivacaftor 的方法

  摘要：

  探索了一种通过吲哚环的一锅氧化裂解然后缩合（Witkop-Winterfeldt 型氧化）从吲哚-3-乙酸酰胺中获得 4-喹诺酮-3-羧酸酰胺的简单方便的方法。该方法的适用范围得到了 20 多个实例的证实，并成功应用于市场上最昂贵的药物 Ivacaftor 的合成。

  DOI：

  10.1002/ejoc.201501048
• 作为产物：
  描述：

  6-氯吲哚 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 生成 2-(6-chloro-1H-indol-3-yl)-2-oxo-N-phenylacetamide
  参考文献：
  名称：

  环的断裂和制造：一种制备 4-喹诺酮-3-羧酸酰胺和昂贵药物 Ivacaftor 的方法

  摘要：

  探索了一种通过吲哚环的一锅氧化裂解然后缩合（Witkop-Winterfeldt 型氧化）从吲哚-3-乙酸酰胺中获得 4-喹诺酮-3-羧酸酰胺的简单方便的方法。该方法的适用范围得到了 20 多个实例的证实，并成功应用于市场上最昂贵的药物 Ivacaftor 的合成。

  DOI：

  10.1002/ejoc.201501048

文献信息

• [EN] PROCESS FOR THE SYNTHESIS OF IVACAFTOR AND RELATED COMPOUNDS<br/>[FR] PROCÉDÉ DE SYNTHÈSE D'IVACAFTOR ET COMPOSÉS ASSOCIÉS
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2016181414A1

  公开（公告）日：2016-11-17

  The present patent discloses a novel one pot two-step process for the synthesis of ivacaftor and related compounds of [Formula (I)], wherein R1, R2, R3, R4, R5, R6, R7 and Ar1 are as described above; its tautomers or pharmaceutically acceptable salts thereof starting from indole acetic acid amides.

  本专利公开了一种新颖的一锅两步合成ivacaftor和相关化合物[公式(I)]的过程，其中R1、R2、R3、R4、R5、R6、R7和Ar1如上所述；其互变异构体或药用盐，起始原料为吲哚乙酸酰胺。
• PROCESS FOR THE SYNTHESIS OF IVACAFTOR AND RELATED COMPOUNDS
  申请人：Council of Scientific and Industrial Research

  公开号：US20180127373A1

  公开（公告）日：2018-05-10

  The present patent discloses a novel one pot two-step process for the synthesis of ivacaftor and related compounds of [Formula (I)], wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and Ar 1 are as described above; its tautomers or pharmaceutically acceptable salts thereof starting from indole acetic acid amides.

  本专利披露了一种新颖的一锅两步法合成伊瓦卡托和相关化合物[式(I)]的过程，其中R1、R2、R3、R4、R5、R6、R7和Ar1如上所述；其互变异构体或药学上可接受的盐，起始物为吲哚乙酸酰胺。
• Process for the synthesis of ivacaftor and related compounds
  申请人：Council of Scientific and Industrial Research

  公开号：US10336703B2

  公开（公告）日：2019-07-02

  The present patent discloses a novel one pot two-step process for the synthesis of ivacaftor and related compounds of [Formula (I)], wherein R1, R2, R3, R4, R5, R6, R7 and Ar1 are as described above; its tautomers or pharmaceutically acceptable salts thereof starting from indole acetic acid amides.

  本专利公开了以吲哚乙酸酰胺为起始原料，合成伊伐卡夫多及相关化合物[式（I）]（其中 R1、R2、R3、R4、R5、R6、R7 和 Ar1 如上所述）及其同系物或药学上可接受的盐的一种新颖的一步法或两步法工艺。
• Discovery of 6-substituted indole-3-glyoxylamides as lead antiprion agents with enhanced cell line activity, improved microsomal stability and low toxicity
  作者：Mark J. Thompson、Jennifer C. Louth、Steven Ferrara、Matthew P. Jackson、Fiona J. Sorrell、Edward J. Cochrane、Joel Gever、Sarah Baxendale、B. Michael Silber、Henry H. Roehl、Beining Chen

  DOI：10.1016/j.ejmech.2011.06.013

  日期：2011.9

  A series of highly potent indole-3-glyoxylamide based antiprion agents was previously characterized, focusing on optimization of structure-activity relationship (SAR) at positions 1-3 of the indole system. New libraries interrogating the SAR at indole C-4 to C-7 now demonstrate that introducing electron-withdrawing substituents at C-6 may improve biological activity by up to an order of magnitude, and additionally confer higher metabolic stability. For the present screening libraries, both the degree of potency and trends in SAR were consistent across two cell line models of prion disease, and the large majority of compounds showed no evidence of toxic effects in zebrafish. The foregoing observations thus make the indole-3-glyoxylamides an attractive lead series for continuing development as potential therapeutic agents against prion disease. (C) 2011 Elsevier Masson SAS. All rights reserved.
• [EN] INDOLE DERIVATIVES FOR THE STIMULATION OF STEM CELL PROLIFERATION<br/>[FR] DÉRIVÉS INDOLE DESTINÉS À STIMULER LA PROLIFÉRATION DE CELLULES SOUCHES
  申请人：UNIV SHEFFIELD

  公开号：WO2010139982A1

  公开（公告）日：2010-12-09

  The present invention relates to indole derivatives of formula (I) and Formula (II) which possess potent antiprion activity and stem cell proliferative properties. The invention also relates to the use of such compounds to treat prion-related diseases and in stem cell therapies.