[[3-(2-amino-1,2-dioxoethyl)-1-[(2,6-dichlorophenyl)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-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indole-4-yl]oxy]acetic acid
• 英文别名: ((3-(2-amino-1,2-dioxoethyl)-1-((2,6-dichlorophenyl)methyl)-2-methyl-1H-indol-4-yl)oxy)acetic acid；[[3-(2-amino-1,2-dioxoethyl)1-[(2,6-dichlorophenyl)methyl]-2-methyl-1H-indol-4-yl]oxy]acetic acid；2-[1-[(2,6-dichlorophenyl)methyl]-2-methyl-3-oxamoylindol-4-yl]oxyacetic acid
• 化学式: C₂₀H₁₆Cl₂N₂O₅
• 分子量: 435.263
• InChiKey: AXRTZAZDPVBRMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

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-[(2,6-dichlorophenyl)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 treating sepsis
  申请人：——

  公开号：US20040110825A1

  公开（公告）日：2004-06-10

  A novel method of treating and/or preventing sepsis.

  一种治疗和/或预防败血症的新方法。
• Combination therapy for the treatment of inflammatory and respiratory diseases
  申请人：——

  公开号：US20030092767A1

  公开（公告）日：2003-05-15

  A pharmaceutical composition for the treatment of Inflammatory Disease or Respiratory Disease in mammals, which comprises, as active ingredients, a neutrophil elastase inhibitor and an sPLA 2 inhibitor.

  一种用于治疗哺乳动物的炎症性疾病或呼吸道疾病的药物组合物，其包括中性粒细胞弹性蛋白酶抑制剂和sPLA2抑制剂作为活性成分。
• Method for the treatment of renal dysfunction with spla2 inhibitors
  申请人：——

  公开号：US20030087944A1

  公开（公告）日：2003-05-08

  A method is disclosed for the treatment of of the symptoms associated with renal dysfunction by administering to an animal in need thereof a therapeutically effective amount of a sPLA 2 inhibitor, such as a 1H-indole-3-glyoxylamide.

  本方法揭示了一种治疗与肾功能障碍相关症状的方法，通过向需要治疗的动物施用一种治疗有效量的 sPLA2 抑制剂，如 1H-吲哚-3-甘酰胺。
• METHOD FOR TRATMENT OF NON-RHEUMATOID ARTHRITIS
  申请人：——

  公开号：US20030119860A1

  公开（公告）日：2003-06-26

  A method is disclosed for the treatment of non-rheumatoid arthritis by administering to a mammal in need thereof a therapeutically effective amount of an sPLA 2 inhibitor.

  本方法涉及通过向需要治疗的哺乳动物施用治疗有效量的sPLA 2 抑制剂来治疗非类风湿性关节炎。