乙基 5-苄氧基吲哚-3-乙醛酸 | 75238-44-7

• 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
• 中文名称: 乙基 5-苄氧基吲哚-3-乙醛酸
• 中文别名: 5-苄氧基吲哚-3-二羟乙酸乙酯；乙基5-苄氧基吲哚-3-乙醛酸
• 英文名称: (5-benzyloxy-indol-3-yl)-glyoxylic acid ethyl ester
• 英文别名: (5-Benzyloxy-indol-3-yl)-glyoxylsaeure-aethylester；ethyl 2-oxo-2-(5-phenylmethoxy-1H-indol-3-yl)acetate
• CAS: 75238-44-7
• 化学式: C₁₉H₁₇NO₄
• mdl: MFCD00022723
• 分子量: 323.348
• InChiKey: GEOTYZHKCQCORI-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于甲醇、四氢呋喃
• 稳定性/保质期：
  远离氧化物、光和热。

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.157
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 储存条件：
  存放在密封容器中，并放置在阴凉、干燥处。请将存储地点远离氧化剂。建议在避光条件下于常温下保存。

反应信息

• 作为反应物：
  描述：

  2-(benzofuran-3-yl)acetamide 、 乙基 5-苄氧基吲哚-3-乙醛酸 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 生成 3-(benzofuran-3-yl)-4-(5-benzyloxy-1H-indol-3-yl)pyrrole-2,5-dione
  参考文献：
  名称：

  Structure-Based Design Leads to the Identification of Lithium Mimetics That Block Mania-like Effects in Rodents. Possible New GSK-3β Therapies for Bipolar Disorders

  摘要：

  More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3 beta inhibitors. The best ligand in this series (having a K-i value of 4.6 nM against GSK-3 beta) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3 beta inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.

  DOI：

  10.1021/ja068969w
• 作为产物：
  描述：

  5-苄氧基吲哚 以 四氢呋喃 、 乙醚 、 乙醇 为溶剂， 生成 乙基 5-苄氧基吲哚-3-乙醛酸
  参考文献：
  名称：

  Structure-Based Design Leads to the Identification of Lithium Mimetics That Block Mania-like Effects in Rodents. Possible New GSK-3β Therapies for Bipolar Disorders

  摘要：

  More than two million American adults, or approximately one percent of the population 18 years or older, suffer from bipolar disorder. Current treatments include the so-called "mood stabilizers," lithium and valproic acid. Both are relatively dated drugs that are only partially effective and produce various undesirable side effects including weight gain. Based upon continued efforts to understand the molecular target for lithium, it now appears that specific inhibitors of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) may mimic the therapeutic action of mood stabilizers and might therefore allow for the design of improved drugs for treating patients with bipolar disorder as well as certain neurodegenerative disorders. Furthermore, the pro-apoptotic properties of the GSK-3 enzyme suggest the possible use of such inhibitors as neuroprotective agents. In fact, neuroprotection may contribute to the treatment of mood disorders. The present chemistry, modeling, and biology efforts have identified 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective GSK-3 beta inhibitors. The best ligand in this series (having a K-i value of 4.6 nM against GSK-3 beta) was studied in a novel mouse model of mania that has recently been validated with several clinically effective mood stabilizers. This study presents the first demonstration of the efficacy of a GSK-3 beta inhibitor in this mouse model of mania. Selective brain penetrable GSK-3 ligands like those described herein become valuable research tools in better defining the role of this multifaceted kinase in both physiological and pathophysiological events.

  DOI：

  10.1021/ja068969w

文献信息

• Pyrano- and thiopyranoindole derivatives, compositions and methods of use
  申请人：Ayerst McKenna and Harrison Ltd.

  公开号：US04003913A1

  公开（公告）日：1977-01-18

  Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of a pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9. The pyrano[3,4-b]indole or thiopyrano[3,4-b]indole derivatives having the amino(lower)alkyl radical only at position 9 possess two substituents at position 1 and may be optionally substituted at position 3,4,5,6,7, and 8; the derivatives having an amino(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7 and 8. The pyrano-and thiopyranoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the preparation and use of these derivatives are also disclosed.

  本发明揭示了具有氨基（较低）烷基基团附加在吡喃[3,4-b]吲哚或硫代吡喃[3,4-b]吲哚核的1位和/或9位，或者具有该基团附加在吡喃[4,3-b]吲哚或硫代吡喃[4,3-b]吲哚核的1位的吡喃吲哚和硫代吡喃吲哚衍生物。氨基（较低）烷基基团的氨基部分可以进一步取代为一或两个较低的烷基基团或并入一个杂环胺基团。仅在1位具有氨基（较低）烷基基团的衍生物在1位进一步取代，并可选择在3、4、5、6、7、8和9位取代。仅在9位具有氨基（较低）烷基基团的吡喃[3,4-b]吲哚或硫代吡喃[3,4-b]吲哚衍生物在1位具有两个取代基，并可选择在3、4、5、6、7和8位取代；在1位和9位均具有氨基（较低）烷基基团的衍生物在1位进一步取代，并可选择在3、4、5、6、7和8位取代。本发明的吡喃和硫代吡喃吲哚衍生物是有用的抗抑郁和抗溃疡剂。还揭示了制备和使用这些衍生物的方法。
• Pharmaceutical method for using pyrano-and thiopyranoindole derivatives
  申请人：Ayerst McKenna and Harrison Ltd.

  公开号：US04041169A1

  公开（公告）日：1977-08-09

  Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of a pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9. The pyrano[3,4-b]indole or thiopyrano[3,4-b]indole derivatives having the amino(lower)alkyl radical only at position 9 possess two substituents at position 1 and may be optionally substituted at position 3,4,5,6,7, and 8; the derivatives having an amino(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7 and 8. The pyrano- and thiopyranoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the preparation and use of these derivatives are also disclosed.

  本发明揭示了一种带有氨基（较低）烷基基团的吡喃并[3,4-b]吲哚或硫代吡喃并[3,4-b]吲哚核的衍生物，其中该基团连接到1和/或9位，或连接到吡喃并[4,3-b]吲哚或硫代吡喃并[4,3-b]吲哚核的1位。氨基（较低）烷基基团的氨基部分可以进一步取代为一个或两个较低的烷基基团或并入到一个杂环胺基团中。仅在1位具有氨基（较低）烷基基团的衍生物在1位进一步取代，并可在3、4、5、6、7、8和9位选择性地取代。仅在9位具有氨基（较低）烷基基团的吡喃并[3,4-b]吲哚或硫代吡喃并[3,4-b]吲哚衍生物在1位具有两个取代基，并可在3、4、5、6、7和8位选择性地取代；在1和9位均具有氨基（较低）烷基基团的衍生物在1位进一步取代，并可在3、4、5、6、7和8位选择性地取代。本发明的吡喃并和硫代吡喃并吲哚衍生物是有用的抗抑郁和抗溃疡药物。还揭示了这些衍生物的制备和使用方法。
• Process for making pyrano- and thiopyranoindole derivatives
  申请人：Ayerst McKenna and Harrison Ltd.

  公开号：US04056537A1

  公开（公告）日：1977-11-01

  Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3, 4, 5, 6, 7, 8, and 9. The derivatives having the amino(lower)alkyl radical only at position 9 possess two substituents at position 1 and may be optionally substituted at position 3, 4, 5, 6, 7, and 8. The derivatives having an amino(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3, 4, 5, 6, 7 and 8. The pyrano- and thiopyranoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the preparation and use of these derivatives are also disclosed.

  本发明披露了一种具有氨基（较低）烷基基团附加到吡喃[3,4-b]吲哚或硫代吡喃[3,4-b]吲哚核的1和9位置中的一个或两个的吡喃吲哚和硫代吡喃吲哚衍生物。氨基（较低）烷基基团的氨基部分可以进一步取代为一个或两个较低的烷基基团或并入一个杂环胺基团中。仅在位置1具有氨基（较低）烷基基团的衍生物在位置1进一步取代，并且可以在位置3、4、5、6、7、8和9选择性地取代。仅在位置9具有氨基（较低）烷基基团的衍生物在位置1具有两个取代基，并且可以在位置3、4、5、6、7和8选择性地取代。在位置1和9均具有氨基（较低）烷基基团的衍生物在位置1进一步取代，并且可以在位置3、4、5、6、7和8选择性地取代。本发明的吡喃和硫代吡喃吲哚衍生物是有用的抗抑郁和抗溃疡药物。还披露了这些衍生物的制备和使用方法。
• Process for preparing pyrano- and thiopyranoindole derivatives
  申请人：Ayerst, McKenna & Harrison Limited

  公开号：US04056538A1

  公开（公告）日：1977-11-01

  Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[ 3,4-b]indole or thiopyrano[3,4-b]indole nucleus are disclosed. The amino position of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3, 4, 5, 6, 7, 8, and 9. The derivatives having the amino(lower)alkyl radical only at position 9 posses two substituents at position 1 and may be optionally substituted at position 3, 4, 5, 6, 7, and 8. The derivatives having an amino(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3, 4, 5, 6, 7 and 8. The pyrano- and thiopyranoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the preparation and use of these derivatives are also disclosed.

  本发明揭示了一种具有氨基（较低）烷基基团附加到吡喃[3,4-b]吲哚或硫代吡喃[3,4-b]吲哚核的1和9位置中的一种或两种的吡喃吲哚和硫代吡喃吲哚衍生物。氨基（较低）烷基基团的氨基位置可以进一步用一或两个较低烷基基团取代或并入杂环胺基团。仅在1位置具有氨基（较低）烷基基团的衍生物在1位置进一步取代，并可在3、4、5、6、7、8和9位置选择性地取代。仅在9位置具有氨基（较低）烷基基团的衍生物在1位置具有两个取代基，并可在3、4、5、6、7和8位置选择性地取代。同时在1和9位置具有氨基（较低）烷基基团的衍生物在1位置进一步取代，并可在3、4、5、6、7和8位置选择性地取代。本发明的吡喃吲哚和硫代吡喃吲哚衍生物是有用的抗抑郁和抗溃疡药物。还揭示了制备和使用这些衍生物的方法。
• Pyranoindole derivatives, compositions and method of use
  申请人：Ayerst, McKenna and Harrison Ltd.

  公开号：US04066779A1

  公开（公告）日：1978-01-03

  Pyranolindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9. The pyrano[3,4-b]indole or thiopyrano[3,4-b]indole derivatives having the amino(lower)alkyl radical only at position 9 possess two substituents at position 1 and may be optionally substituted at position 3,4,5,6,7, and 8; the derivatives having an amino-(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7 and 8. The pyrano- and thiopyranindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the preparation and use of these derivatives are also disclosed.

  本发明揭示了具有氨基(较低)烷基基团结合到吡喃[3,4-b]吲哚或硫代吡喃[3,4-b]吲哚核的1和9位置之一或两个位置上，或者具有该基团结合到吡喃[4,3-b]吲哚或硫代吡喃[4,3-b]吲哚核的1位置的吡喃吲哚和硫代吡喃吲哚衍生物。氨基(较低)烷基基团的氨基部分可以进一步被一个或两个较低的烷基基团取代或并入到一个杂环胺基团中。仅在1位置具有氨基(较低)烷基基团的衍生物在1位置进一步取代，并且可以在3、4、5、6、7、8和9位置可选地取代。仅在9位置具有氨基(较低)烷基基团的吡喃[3,4-b]吲哚或硫代吡喃[3,4-b]吲哚衍生物在1位置具有两个取代基，并且可以在3、4、5、6、7和8位置可选地取代；在1和9位置都具有氨基(较低)烷基基团的衍生物在1位置进一步取代，并且可以在3、4、5、6、7和8位置可选地取代。本发明的吡喃和硫代吡喃吲哚衍生物是有用的抗抑郁和抗溃疡剂。本发明还揭示了这些衍生物的制备和使用方法。