methyl 2-[4-[(4-amino-2-carbamoyl-1H-indol-5-yl)oxy]-3-methoxyphenyl]acetate | 1080522-16-2

• 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: methyl 2-[4-[(4-amino-2-carbamoyl-1H-indol-5-yl)oxy]-3-methoxyphenyl]acetate
• CAS: 1080522-16-2
• 化学式: C₁₉H₁₉N₃O₅
• 分子量: 369.377
• InChiKey: FGYWGRLTTXDPST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 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：
  130
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-[4-[(4-amino-2-carbamoyl-1H-indol-5-yl)oxy]-3-methoxyphenyl]acetate 在 吡啶 、 三氯氧磷 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 2-(4-(2-cyano-4-(2,4-dichlorophenylsulfonamido)-1H-indol-5-yloxy)-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：

  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

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。
• US7960567B2
  申请人：——

  公开号：US7960567B2

  公开（公告）日：2011-06-14
• [EN] COMPOUNDS AND METHODS USEFUL FOR TREATING ASTHMA AND ALLERGIC INFLAMMATION<br/>[FR] COMPOSÉS ET PROCÉDÉS UTILES POUR LE TRAITEMENT DE L'ASTHME ET DE L'INFLAMMATION ALLERGIQUE
  申请人：AMGEN INC

  公开号：WO2008137027A2

  公开（公告）日：2008-11-13

  [EN] 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.
  [FR] La présente invention concerne des composés, compositions et procédés qui sont utiles dans le traitement des maladies et conditions inflammatoires et des maladies liées aux troubles immunitaires. En particulier, l'invention concerne des composés qui régulent la fonction et/ou l'expression des protéines impliquées dans les maladies atopiques, les conditions inflammatoires et le cancer. Les composés de cette invention sont des dérivés d'acides carboxyliques.