tert-butyl 4-[(2-methyl-1H-indol-5-yl)oxy]butanoate | 697753-62-1

• 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: tert-butyl 4-[(2-methyl-1H-indol-5-yl)oxy]butanoate
• CAS: 697753-62-1
• 化学式: C₁₇H₂₃NO₃
• 分子量: 289.375
• InChiKey: XXNIYCKWFFNVSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  51.32
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(2-methyl-1H-indol-5-yl)oxy]butanoate 在 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.42h， 生成
  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
• 作为产物：
  描述：

  5-羟基-2-甲基吲哚 、 4-溴丁酸叔丁酯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 72.0h， 以77%的产率得到tert-butyl 4-[(2-methyl-1H-indol-5-yl)oxy]butanoate
  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