1,3,4,5-四氢-吡喃并[4,3-b]吲哚 | 784143-97-1

• 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
• 中文名称: 1,3,4,5-四氢-吡喃并[4,3-b]吲哚
• 中文别名: 1,3,4,5-四氢-吡喃并[4,3-B]吲哚
• 英文名称: 1,3,4,5-tetrahydro-pyrano[4,3-b]indole
• 英文别名: 1,3,4,5-Tetrahydropyrano[4,3-b]indole
• CAS: 784143-97-1
• 化学式: C₁₁H₁₁NO
• 分子量: 173.214
• InChiKey: BUQKZKMCGKVWEV-UHFFFAOYSA-N

物化性质

• 沸点：
  349.8±32.0 °C(Predicted)
• 密度：
  1.239±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  25
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1,3,4,5-四氢-吡喃并[4,3-b]吲哚 在 potassium cyanide 、 羟胺 、 sodium hydride 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 16.75h， 生成 4-((3,4-dihydropyrano[4,3-b]indol-5(1H)-yl)methyl)-N-hydroxybenzamide
  参考文献：
  名称：

  Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated

  摘要：

  The discovery of isozyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biological functions of individual HDACs and for validating HDACs as drug targets. The isozyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no studies toward selective HDAC10 inhibitors have been published. Using two complementary assays, we found Tubastatin A, an HDAC6 inhibitor, to potently bind HDAC10. We synthesized Tubastatin A derivatives and found that a basic amine in the cap group was required for strong HDAC10 binding. HDAC10 inhibitors mimicked knockdown by causing dose-dependent accumulation of acidic vesicles in a neuroblastoma cell line. Furthermore, docking into human HDAC10 homology models indicated that a hydrogen bond between a cap group nitrogen and the gatekeeper residue Glu272 was responsible for potent HDAC10 binding. Taken together, our data provide an optimal platform for the development of HDAC10-selective inhibitors, as exemplified with the Tubastatin A scaffold.

  DOI：

  10.1021/acs.jmedchem.8b01936
• 作为产物：
  描述：

  四氢吡喃酮 、 邻氯苯胺 在 二(三叔丁基膦)钯 potassium phosphate 、 magnesium sulfate 、 溶剂黄146 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 以98%的产率得到1,3,4,5-四氢-吡喃并[4,3-b]吲哚
  参考文献：
  名称：

  通过氯代苯胺和氯氨基吡啶与酮的直接环合反应，实现柔性的钯催化的吲哚和氮杂吲哚合成。

  摘要：

  DOI：

  10.1002/anie.200460122

文献信息

• 一种噻喃[4,3-b]吲哚类化合物及其制备方法 和应用
  申请人：华南农业大学

  公开号：CN108558905B

  公开（公告）日：2021-03-12

  本发明公开了一种噻喃[4,3‑b]吲哚类化合物及其制备方法和应用。所述化合物的结构如式（Ⅰ）所示：；其中R1～R5不同时全部为氢。本发明所述化合物对水稻纹枯病菌具有优异的抑制菌丝生长活性、离体叶片保护活性、活体保护活性以及活体治疗活性，其作用甚至优于阳性对照药物，对于水稻纹枯病的预防和/或治疗具有重大的应用价值。
• A Flexible, Palladium-Catalyzed Indole and Azaindole Synthesis by Direct Annulation of Chloroanilines and Chloroaminopyridines with Ketones
  作者：Marc Nazaré、Claudia Schneider、Andreas Lindenschmidt、David William Will

  DOI：10.1002/anie.200460122

  日期：2004.8.27
• Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated
  作者：Magalie Géraldy、Michael Morgen、Peter Sehr、Raphael R. Steimbach、Davide Moi、Johannes Ridinger、Ina Oehme、Olaf Witt、Mona Malz、Mauro S. Nogueira、Oliver Koch、Nikolas Gunkel、Aubry K. Miller

  DOI：10.1021/acs.jmedchem.8b01936

  日期：2019.5.9

  The discovery of isozyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biological functions of individual HDACs and for validating HDACs as drug targets. The isozyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no studies toward selective HDAC10 inhibitors have been published. Using two complementary assays, we found Tubastatin A, an HDAC6 inhibitor, to potently bind HDAC10. We synthesized Tubastatin A derivatives and found that a basic amine in the cap group was required for strong HDAC10 binding. HDAC10 inhibitors mimicked knockdown by causing dose-dependent accumulation of acidic vesicles in a neuroblastoma cell line. Furthermore, docking into human HDAC10 homology models indicated that a hydrogen bond between a cap group nitrogen and the gatekeeper residue Glu272 was responsible for potent HDAC10 binding. Taken together, our data provide an optimal platform for the development of HDAC10-selective inhibitors, as exemplified with the Tubastatin A scaffold.