5-(2-methoxy-4-(2-methoxy-2-oxoethyl)phenoxy)-4-nitro-1H-indole-2-carboxylic acid | 1080522-12-8

• 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-(2-methoxy-4-(2-methoxy-2-oxoethyl)phenoxy)-4-nitro-1H-indole-2-carboxylic acid
• 英文别名: 5-[2-methoxy-4-(2-methoxy-2-oxoethyl)phenoxy]-4-nitro-1H-indole-2-carboxylic acid
• CAS: 1080522-12-8
• 化学式: C₁₉H₁₆N₂O₈
• 分子量: 400.345
• InChiKey: JNESAAGRSXFLIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-(2-methoxy-4-(2-methoxy-2-oxoethyl)phenoxy)-4-nitro-1H-indole-2-carboxylic acid 在 N-甲基吗啉 、 ammonium hydroxide 、 palladium on activated charcoal 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙酸乙酯 为溶剂， 生成 methyl 2-[4-[(4-amino-2-carbamoyl-1H-indol-5-yl)oxy]-3-methoxyphenyl]acetate
  参考文献：
  名称：

  Solving time-dependent CYP3A4 inhibition for a series of indole-phenylacetic acid dual antagonists of the PGD2 receptors CRTH2 and DP

  摘要：

  Based on their structural similarity to previously described compound AMG 009, indole-phenyl acetic acids were proposed to be potent dual inhibitors of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2 or DP2) and prostanoid D receptor (DP or DP1). This series was equipotent to AMG 009 in binding assays against both receptors but exhibited decreased serum shift. We discovered early in the optimization of these indole-phenylacetic acid compounds that they demonstrated CYP3A4 time-dependent inhibition (TDI). Hypothesizing that the source of TDI was the indole core we modified the 1,2,3-substitution to eventually afford a highly potent modulator of CRTH2 and DP which did not exhibit TDI. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.092
• 作为产物：
  描述：

  ethyl 5-(4-(2-ethoxy-2-oxoethyl)-2-methoxyphenoxy)-4-nitro-1H-indole-2-carboxylate 在 lithium hydroxide 、 三甲基氯硅烷 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 5-(2-methoxy-4-(2-methoxy-2-oxoethyl)phenoxy)-4-nitro-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  WO2008/137027

  摘要：

  公开号：

文献信息

• COMPOUNDS AND METHODS USEFUL FOR TREATING ASTHMA AND ALLERGIC INFLAMMATION
  申请人：Brown Matthew

  公开号：US20080312270A1

  公开（公告）日：2008-12-18

  Compounds, compositions and methods that are useful in the treatment of inflammatory and immune-related diseases and conditions are provided herein. In particular, the invention provides compounds which modulate the function and/or expression of proteins involved in atopic diseases, inflammatory conditions and cancer. The subject compounds are carboxylic acid derivatives.

  本文提供了在治疗炎症和免疫相关疾病和病况方面有用的化合物、组合物和方法。具体而言，本发明提供了调节参与过敏性疾病、炎症病症和癌症的蛋白质的功能和/或表达的化合物。所述化合物为羧酸衍生物。
• Compounds and methods useful for treating asthma and allergic inflammation
  申请人：Amgen Inc.

  公开号：US07960567B2

  公开（公告）日：2011-06-14

  Compounds, compositions and methods that are useful in the treatment of inflammatory and immune-related diseases and conditions are provided herein. In particular, the invention provides compounds which modulate the function and/or expression of proteins involved in atopic diseases, inflammatory conditions and cancer. The subject compounds are carboxylic acid derivatives.

  本文提供了用于治疗炎症和免疫相关疾病和病况的化合物、组合物和方法。特别地，本发明提供了调节参与特应性疾病、炎症病况和癌症的蛋白质的功能和/或表达的化合物。这些化合物是羧酸衍生物。
• WO2008/137027
  申请人：——

  公开号：——

  公开（公告）日：——
• COMPOUNDS AS CRTH2 AND/OR PGD2 RECEPTORS MODULATORS AND THEIR USE FOR TREATING ASTHMA AND ALLERGIC INFLAMMATION
  申请人：Amgen Inc.

  公开号：EP2164828A2

  公开（公告）日：2010-03-24
• US7960567B2
  申请人：——

  公开号：US7960567B2

  公开（公告）日：2011-06-14