(3-aminooxalyl-1-benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid tert-butyl ester | 936625-39-7

• 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-aminooxalyl-1-benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid tert-butyl ester
• 英文别名: Tert-butyl 2-(1-benzyl-2-methyl-3-oxamoylindol-4-yl)oxyacetate
• CAS: 936625-39-7
• 化学式: C₂₄H₂₆N₂O₅
• 分子量: 422.481
• InChiKey: AQRSFPFMUAZBDC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3-aminooxalyl-1-benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以75%的产率得到((3-(2-amino-1,2-dioxoethyl)-2-methyl-1-(phenylmethyl)-1H-indol-4-yl)oxy)acetic acid
  参考文献：
  名称：

  WO2007/56279

  摘要：

  公开号：
• 作为产物：
  描述：

  tert-butyl [(2-methyl-1H-indol-4-yl)oxy]acetate 在 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 10.25h， 生成 (3-aminooxalyl-1-benzyl-2-methyl-1H-indol-4-yloxy)-acetic acid tert-butyl ester
  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

• Phospholipase inhibitors, including multi-valent phospholipase inhibitors, and use thereof, including as lumen-localized phospholipase inhibitors
  申请人：Chang Han-Ting

  公开号：US20070135383A1

  公开（公告）日：2007-06-14

  The present invention provides methods and compositions for the treatment of phospholipase-related conditions. In particular, the invention provides a method of treating insulin-related, weight-related conditions and/or cholesterol-related conditions in an animal subject. The method generally involves the administration of a non-absorbed and/or effluxed phospholipase A2 inhibitor that is localized in a gastrointestinal lumen.

  本发明提供了治疗磷脂酶相关疾病的方法和组合物。具体地，本发明提供了一种用于治疗动物主体中的胰岛素相关、体重相关和/或胆固醇相关疾病的方法。该方法通常涉及在胃肠道腔中定位的非吸收和/或外流的磷脂酶A2抑制剂的给药。
• WO2007/56279
  申请人：——

  公开号：——

  公开（公告）日：——
• Inhibition of the complete set of mammalian secreted phospholipases A2 by indole analogues
  作者：Brian P. Smart、Ying H. Pan、Amanda K. Weeks、James G. Bollinger、Brian J. Bahnson、Michael H. Gelb

  DOI：10.1016/j.bmc.2004.01.022

  日期：2004.4

  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.
• [EN] PHOSPHOLIPASE INHIBITORS, INCLUDING MULTI-VALENT PHOSPHOLIPASE INHIBITORS, AND USE THEREOF, INCLUDING AS LUMEN-LOCALIZED PHOSPHOLIPASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHOLIPASES, NOTAMMENT INHIBITEURS DE PHOSPHOLIPASES MULTIVALENTS, LEUR UTILISATION, NOTAMMENT EN TANT QU'INHIBITEURS DE PHOSPHOLIPASES LOCALISES DANS UNE LUMIERE
  申请人：ILYPSA INC

  公开号：WO2007056279A2

  公开（公告）日：2007-05-18

  [EN] The present invention provides methods and compositions for the treatment of phospholipase-related conditions. In particular, the invention provides a method of treating insulin-related, weight-related conditions and/or cholesterol-related conditions in an animal subject. The method generally involves the administration of a non-absorbed and/or effluxed phospholipase A2 inhibitor that is localized in a gastrointestinal lumen.
  [FR] La présente invention concerne des méthodes et des compositions pour le traitement d'états liés aux phospholipases. En particulier, l'invention concerne une méthode de traitement d'états liés à l'insuline, liés au poids et/ou liés au cholestérol chez un sujet animal. La méthode consiste généralement à administrer un inhibiteur de phospoholipases A2 non absorbé et/ou résultant d'un écoulement qui est localisé dans une lumière gastro-intestinale.
• The First Potent Inhibitor of Mammalian Group X Secreted Phospholipase A₂:  Elucidation of Sites for Enhanced Binding
  作者：Brian P. Smart、Rob C. Oslund、Laura A. Walsh、Michael H. Gelb

  DOI：10.1021/jm060136t

  日期：2006.5.1

  Using the X-ray structure of human group X secreted phospholipase A(2) (hGX), we carried out structure-based design of indole-based inhibitors and prepared the compounds using a new synthetic route. The most potent compound inhibited hGX and the mouse orthologue with an IC50 of 75 nM. This compound is the most potent hGX inhibitor reported to date and was also found to inhibit a subset of the other mouse and human sPLA(2)s.