3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile

• 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: 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile
• 英文别名: 3-(4-hydroxybutanoyl)-1H-indole-5-carbonitrile
• 化学式: C₁₃H₁₂N₂O₂
• 分子量: 228.25
• InChiKey: COUOYQOKDASMMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  76.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile 在 盐酸 、 氨 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.08h， 生成 维拉佐酮
  参考文献：
  名称：

  [EN] IMPROVED PROCESS FOR PREPARING BENZOFURAN-2-CARBOXAMIDE DERIVATIVES
  [FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE DÉRIVÉS DE BENZOFURAN-2-CARBOXAMIDE

  摘要：

  公开号：

  WO2014006637A3
• 作为产物：
  描述：

  3-(4-氯丁酰基)-1H-吲哚-5-甲腈 在 三乙胺 作用下， 以 水 、 乙腈 为溶剂， 反应 5.0h， 以81%的产率得到3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile
  参考文献：
  名称：

  Design, synthesis and evaluation of vilazodone-tacrine hybrids as multitarget-directed ligands against depression with cognitive impairment

  摘要：

  Depression, a severe mental disease, is greatly difficult to treat and easy to induce other neuropsychiatric symptoms, the most frequent one is cognitive impairment. In this study, a series of novel vilazodonetacrine hybrids were designed, synthesized and evaluated as multitarget agents against depression with cognitive impairment. Most compounds exhibited good multitarget activities and appropriate blood-brain barrier permeability. Specifically, compounds 1d and 2a exhibited excellent 5-HT1A agonist activities (1d, EC50 = 0.36 +/- 0.08 nM; 2a, EC50 = 0.58 +/- 0.14 nM) and 5-HT reuptake inhibitory activities (1d, IC50 = 20.42 +/- 6.60 nM; 2a, IC50 = 22.10 +/- 5.80 nM). In addition, they showed moderate ChE inhibitory activities (1d, AChE IC50 = 1.72 +/- 0.217 mu M, BuChE IC50 = 0.34 +/- 0.03 mu M; 2a, AChE IC50 = 2.36 +/- 0.34 mu M, BuChE IC50 = 0.10 +/- 0.01 mu M). Good multitarget activities with goodt blood-brain barrier permeability of 1d and 2a make them good lead compounds for the further study of depression with cognitive impairment. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.04.037

文献信息

• PROCESS FOR PREPARING VILAZODONE HYDROCHLORIDE
  申请人：Ferrari Massimo

  公开号：US20130225818A1

  公开（公告）日：2013-08-29

  The present invention relates, in a first aspect, to a process preparing vilazodone hydrochloride that comprises the reaction of 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile with 5-piperazin-1-yl-benzofuran-2-carboxylate methyl hydrochloride with the formation of a 1,4-piperazine, with subsequent dehydration, hydrogenation and treatment with ammonia, to obtain vilazodone in free base form that is then converted into the hydrochloride thereof.

  本发明涉及一种制备维拉唑酮盐酸盐的过程，其中包括将3-(4-氯-1-羟基丁基)-1H-吲哚-5-羧腈与5-哌嗪-1-基苯并呋喃-2-羧酸甲酯反应，形成1,4-哌嗪，随后脱水、加氢并用氨处理，以获得维拉唑酮的游离碱形式，然后将其转化为盐酸盐形式。
• IMPROVED PROCESS FOR PREPARING BENZOFURAN-2-CARBOXAMIDE DERIVATIVES
  申请人：SYMED LABS LIMITED

  公开号：US20150322030A1

  公开（公告）日：2015-11-12

  Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile.

  本文提供了一种新的、商业上可行且具有工业优势的方法，用于高产率和高纯度制备苯并呋喃-2-羧酰胺衍生物及其中间体，或其药学上可接受的盐。特别提供了一种新的、商业上可行且具有工业优势的方法，用于高产率和高纯度制备维拉唑酮或其药学上可接受的盐。本文还提供了一种改进的、商业上可行的方法，使用新的中间体化合物3-(4-羟基丁酰基)-1H-吲哚-5-碳腈，高产率和高纯度地制备3-(4-羟基丁基)-1H-吲哚-5-碳腈。
• PROCESS FOR PREPARING BENZOFURAN-2-CARBOXAMIDE DERIVATIVES
  申请人：SYMED LABS LIMITED

  公开号：US20170267655A1

  公开（公告）日：2017-09-21

  Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile.

  本文提供了一种新颖、商业可行和工业优势的过程，用于制备苯并呋喃-2-羧酰胺衍生物及其中间体，或其药用可接受盐，产率和纯度高。本文特别提供了一种新颖、商业可行和工业优势的过程，用于制备维拉唑酮或其药用可接受盐，产率和纯度高。本文还提供了一种改进的、商业可行的过程，用于利用新的中间化合物3-(4-羟基丁酰基)-1H-吲哚-5-碳腈，高产高纯地制备3-(4-羟基丁基)-1H-吲哚-5-碳腈。
• Process for preparing benzofuran-2-carboxamide derivatives
  申请人：SYMED LABS LIMITED

  公开号：US09315456B2

  公开（公告）日：2016-04-19

  Provided herein are novel, commercially viable and industrially advantageous processes for the preparation of benzofuran-2-carboxamide derivatives and their intermediates, or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided particularly herein are novel, commercially viable and industrially advantageous processes for the preparation of vilazodone or a pharmaceutically acceptable salt thereof in high yield and purity. Provided also herein is an improved and commercially viable process for the preparation of 3-(4-hydroxybutyl)-1H-indole-5-carbonitrile, in high yield and purity, using novel intermediate compound 3-(4-hydroxybutyryl)-1H-indole-5-carbonitrile.

  本文提供了制备苯并呋喃-2-羧酰胺衍生物及其中间体或其药学上可接受的盐的新颖、商业化和工业上优越的工艺，其产率和纯度高。特别提供了一种制备维拉唑酮或其药学上可接受的盐的新颖、商业化和工业上优越的工艺，其产率和纯度高。本文还提供了一种改进的、商业化的制备3-(4-羟基丁基)-1H-吲哚-5-碳腈的工艺，使用新颖的中间体化合物3-(4-羟基丁酰基)-1H-吲哚-5-碳腈，产率和纯度高。
• US8802851B2
  申请人：——

  公开号：US8802851B2

  公开（公告）日：2014-08-12