[[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indole-4-yl]oxy]acetic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indole-4-yl]oxy]acetic acid
• 英文别名: ((3-(2-amino-1,2-dioxoethyl)-1-(4-fluorophenylmethyl)-2-methyl-1H-indol-4-yl)oxy)acetic acid；[[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid；2-[1-[(4-fluorophenyl)methyl]-2-methyl-3-oxamoylindol-4-yl]oxyacetic acid
• 化学式: C₂₀H₁₇FN₂O₅
• 分子量: 384.364
• InChiKey: OPKMRNPUBMWWQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  tert-butyl ({3-[amino(oxo)acetyl]-2-methyl-1H-indol-4-yl}oxy)acetate 在 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 4.17h， 生成 [[3-(2-amino-1,2-dioxoethyl)-1-[(4-fluorophenyl)methyl]-2-methyl-1H-indole-4-yl]oxy]acetic acid
  参考文献：
  名称：

  Inhibition of the complete set of mammalian secreted phospholipases A2 by indole analogues

  摘要：

  Structure-guided design was employed in a search for potent and selective inhibitors of mammalian secreted phospholipases A(2) (sPLA(2)S)- Using the X-ray structures of human groups IIA and X sPLA(2)S (hGIIA and hGX) as templates, homology structural models were made for the other human and mouse sPLA(2)S (hGIB, mGIB, mGIIA, mGIIC, hGIID, mGIID, hGIIE, mGIIE, hGIIF, mGIIF, hGV, mGV, and mGX). Me-Indoxam is a previously discovered indole analogue that binds tightly to many sPLA(2)S, and the X-ray structure of the hGX-Me-Indoxam complex was determined at a resolution of 2.0 Angstrom. Modeling suggests that the residues near the N-1-substituent of Me-Indoxam vary significantly among the mammalian sPLA(2)S, and therefore a library of 83 N-1-variants was prepared by parallel synthesis. Several Me-Indoxam analogues bearing a 4-(2-oxy-ethanoic acid) side chain were potent inhibitors (IC50 <0.05 muM) of hGIIA, mGIIA, mGIIC, hGIIE, mGIIE, hGV, and mGV, while they displayed intermediate potency (0.05-5 muM) against hGIB, mGIB, hGX, and mGX, and poorly inhibited (> 5 muM) hGIID, mGIID, hGIIF, and mGIIF. Me-Indoxam analogues bearing a 5-(4-oxy-butanoic acid) side chain were generally less potent inhibitors. Although no compounds were found to be highly specific for a single human or mouse sPLA(2), combinations of Me-Indoxam analogues were discovered that could be used to distinguish the action of various sPLA(2)S in cellular events. For example, Me-Indoxam and compound 5 are approximately 5-fold more potent on hGIIA than on hGV, and compound 21 is 10-fold more potent on hGV versus hGIIA. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.01.022

文献信息

• 1H-indole-3-glyoxylamide SPLA.sub.2 inhibitors
  申请人：Eli Lilly and Company

  公开号：US05654326A1

  公开（公告）日：1997-08-05

  A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids for treatment of conditions such as septic shock.

  一种新型的1H-吲哚-3-甘氧酰胺类化合物被揭示，以及利用这类吲哚化合物抑制sPLA.sub.2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病的方法。
• Method for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds
  申请人：Shionogi & Co., Ltd.

  公开号：US20030149000A1

  公开（公告）日：2003-08-07

  A method or composition is disclosed for the treatment of disorders associated with apoptosis using N-heterocyclic glyoxylamide compounds.

  本文揭示了使用N-杂环甘酰胺化合物治疗与凋亡相关的疾病的方法或组合物。
• 1H-indole-3-glyoxylamide sPLA.sub.2 inhibitors
  申请人：Eli Lilly and Company

  公开号：US05733923A1

  公开（公告）日：1998-03-31

  A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids for treatment of conditions such as septic shock.

  一种新型的1H-吲哚-3-甘氧酰胺类化合物被披露，以及使用这些吲哚化合物抑制sPLA.sub.2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病的方法。
• 1H-indole-3-glyoxylamide sPLA2 inhibitors
  申请人：Eli Lilly and Company

  公开号：US06433001B1

  公开（公告）日：2002-08-13

  A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.

  一类新型的1H-吲哚-3-乙酰胺基甲酸酰胺被揭示，以及使用这种吲哚化合物来抑制sPLA2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病的方法。
• Process for preparing 1H-indole-3-glyoxylamides
  申请人：Eli Lilly and Company

  公开号：US05919943A1

  公开（公告）日：1999-07-06

  A class of novel 1H-indole-3-glyoxylamides is disclosed together with the use of such indole compounds for inhibiting sPLA.sub.2 mediated release of fatty acids for treatment of conditions such as septic shock.

  本发明揭示了一类新型1H-吲哚-3-甘氧酰胺化合物，以及利用这些吲哚化合物抑制sPLA.sub.2介导的脂肪酸释放，用于治疗诸如感染性休克等疾病的方法。