2-[4-[[4-[(2,4-dichlorophenyl)sulfonylamino]-2-propyl-1H-indol-5-yl]oxy]-3-methoxyphenyl]acetic acid | 1612849-07-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-[[4-[(2,4-dichlorophenyl)sulfonylamino]-2-propyl-1H-indol-5-yl]oxy]-3-methoxyphenyl]acetic acid
• CAS: 1612849-07-6
• 化学式: C₂₆H₂₄Cl₂N₂O₆S
• 分子量: 563.458
• InChiKey: KUEQWQLAGLHEAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(4-(4-amino-2-nitrophenoxy)-3-methoxyphenyl)acetic acid 在 吡啶 、 硫酸 、 potassium tert-butylate 、 水 、 tin(ll) chloride 、 lithium hydroxide 作用下， 以 甲醇 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 生成 2-[4-[[4-[(2,4-dichlorophenyl)sulfonylamino]-2-propyl-1H-indol-5-yl]oxy]-3-methoxyphenyl]acetic acid
  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

• Solving time-dependent CYP3A4 inhibition for a series of indole-phenylacetic acid dual antagonists of the PGD2 receptors CRTH2 and DP
  作者：Michael G. Johnson、Jim (Jiwen) Liu、An-Rong Li、Bettina van Lengerich、Sophie Wang、Julio C. Medina、Tassie L. Collins、Jay Danao、Lisa Seitz、Angela Willee、Warren D’Souza、Alison L. Budelsky、Peter W. Fan、Simon G.W. Wong

  DOI：10.1016/j.bmcl.2014.04.092

  日期：2014.7

  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.