(5-chloro-7-fluoro-1H-indol-2-yl)-(4-methyl-1,4-diazepan-1-yl)methanone | 1394078-64-8

• 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-chloro-7-fluoro-1H-indol-2-yl)-(4-methyl-1,4-diazepan-1-yl)methanone
• CAS: 1394078-64-8
• 化学式: C₁₅H₁₇ClFN₃O
• 分子量: 309.771
• InChiKey: LCBUMKUXFYYSIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  39.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-氯-7-氟-1H-吲哚-2-羧酸乙酯 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.17h， 生成 (5-chloro-7-fluoro-1H-indol-2-yl)-(4-methyl-1,4-diazepan-1-yl)methanone
  参考文献：
  名称：

  Detailed structure–activity relationship of indolecarboxamides as H4 receptor ligands

  摘要：

  A series of 76 derivatives of the indolecarboxamide 1 were synthesized, which allows a detailed SAR investigation of this well known scaffold. The data enable the definition of a predictive QSAR model which identifies several compounds with an activity comparable to 1. A selection of these new H4R antagonists was synthesized and a comparison of predicted and measured values demonstrates the robustness of the model (47-55). In addition to the H-4-receptor activity general CMC and DMPK properties were investigated. Some of the new analogs are not only excellently soluble, but display a significantly increased half-life in mouse liver microsomes as well. These properties qualify these compounds as a possible new standard for future in vivo studies (e.g 51, 52 and 55). Moreover, the current studies also provide valuable information on the potential receptor ligand interactions between the indolcarboxamides and the H4R protein. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.016

文献信息

• Detailed structure–activity relationship of indolecarboxamides as H4 receptor ligands
  作者：Harald Engelhardt、Iwan J.P. de Esch、Daniel Kuhn、Rogier A. Smits、Obbe P. Zuiderveld、Julia Dobler、Moriz Mayer、Sebastian Lips、Heribert Arnhof、Dirk Scharn、Eric E.J. Haaksma、Rob Leurs

  DOI：10.1016/j.ejmech.2012.06.016

  日期：2012.8

  A series of 76 derivatives of the indolecarboxamide 1 were synthesized, which allows a detailed SAR investigation of this well known scaffold. The data enable the definition of a predictive QSAR model which identifies several compounds with an activity comparable to 1. A selection of these new H4R antagonists was synthesized and a comparison of predicted and measured values demonstrates the robustness of the model (47-55). In addition to the H-4-receptor activity general CMC and DMPK properties were investigated. Some of the new analogs are not only excellently soluble, but display a significantly increased half-life in mouse liver microsomes as well. These properties qualify these compounds as a possible new standard for future in vivo studies (e.g 51, 52 and 55). Moreover, the current studies also provide valuable information on the potential receptor ligand interactions between the indolcarboxamides and the H4R protein. (C) 2012 Elsevier Masson SAS. All rights reserved.