4-hydroxy-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one | 1620658-57-2

• 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: 4-hydroxy-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one
• 英文别名: 4-hydroxy-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indol-1-one；4-Hydroxy-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one
• CAS: 1620658-57-2
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: VHYVVIDYDAGJDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-hydroxy-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one 在 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 18.0h， 生成 2-benzyl-4-ethoxy-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indol-1-one
  参考文献：
  名称：

  Convenient Synthesis of N-Heterocycle-Fused Tetrahydro-1,4-Diazepinones

  摘要：

  介绍了合成四氢-4H-吡唑并[1,5-a][1,4]二氮杂卓-4-酮、四氢[1,4]二氮杂卓[1,2-a]吲哚-1-酮和四氢-1H-苯并[4,5]咪唑并[1,2-a][1,4]二氮杂卓-1-酮衍生物的一般方法。研究人员开发了一种区域选择性策略，从易于获得的 3(5)-芳基-或甲基-1H-吡唑-5(3)-羧酸乙酯合成 1-(环氧乙烷-2-基甲基)-1H-吡唑-5-羧酸乙酯。得到的中间体进一步用胺处理，导致环氧乙烷开环和直接环化，产生目标吡唑并[1,5-a][1,4]二氮杂卓-4-酮。目前的研究采用了简单的两步合成法，并成功地将 1H-indole- 乙酯和 1H-苯并[d]咪唑-2-甲酸乙酯功能化。融合杂环化合物的结构通过 1H、13C 和 15N-NMR 光谱以及 HRMS 调查得到了证实。

  DOI：

  10.3390/molecules27248666
• 作为产物：
  描述：

  1-烯丙基-1H-吲哚-2-羧酸 在 2,6-二甲基吡啶 、 N-碘代丁二酰亚胺 、 palladium 10% on activated carbon 、 氨 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， -20.0~20.0 ℃ 、1.0 MPa 条件下， 反应 67.5h， 生成 4-hydroxy-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of tetrahydro[1,4]diazepino[1,2-a]indol-1-ones as cyclin-dependent kinase inhibitors

  摘要：

  New series of 2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-ones and 3,4,5,10-tetrahydro-2H-diazepino[3,4-b]indol-1-ones have been synthesized through an iodolactonisation/lactone-to-lactam rearrangement sequence. These compounds were evaluated as potential protein kinase inhibitors (CDK1, CDK5 and GSK-3). 11-Iodo-2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-one derivatives exhibited sub-micromolar inhibitory activity against cyclin-dependent kinases. Docking studies were realized to determine the binding mode of the inhibitors into the ATP binding domain of the CDK5 catalytic site. Our result highlighted two weak Van-der-Waals bonding interactions established between the iodine atom and both phenyl group of Phe 80 and ammonium end of Lys 33.

  DOI：

  10.1016/j.ejmech.2014.06.063

文献信息

• Synthesis and biological evaluation of tetrahydro[1,4]diazepino[1,2-a]indol-1-ones as cyclin-dependent kinase inhibitors
  作者：Aurélien Putey、Guy Fournet、Olivier Lozach、Lionel Perrin、Laurent Meijer、Benoît Joseph

  DOI：10.1016/j.ejmech.2014.06.063

  日期：2014.8

  New series of 2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-ones and 3,4,5,10-tetrahydro-2H-diazepino[3,4-b]indol-1-ones have been synthesized through an iodolactonisation/lactone-to-lactam rearrangement sequence. These compounds were evaluated as potential protein kinase inhibitors (CDK1, CDK5 and GSK-3). 11-Iodo-2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-one derivatives exhibited sub-micromolar inhibitory activity against cyclin-dependent kinases. Docking studies were realized to determine the binding mode of the inhibitors into the ATP binding domain of the CDK5 catalytic site. Our result highlighted two weak Van-der-Waals bonding interactions established between the iodine atom and both phenyl group of Phe 80 and ammonium end of Lys 33.
• Convenient Synthesis of N-Heterocycle-Fused Tetrahydro-1,4-Diazepinones
  作者：Karolina Dzedulionytė、Melita Veikšaitė、Vít Morávek、Vida Malinauskienė、Greta Račkauskienė、Algirdas Šačkus、Asta Žukauskaitė、Eglė Arbačiauskienė

  DOI：10.3390/molecules27248666

  日期：——

  A general approach towards the synthesis of tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one, tetrahydro[1,4]diazepino[1,2-a]indol-1-one and tetrahydro-1H-benzo[4,5]imidazo[1,2-a][1,4]diazepin-1-one derivatives was introduced. A regioselective strategy was developed for synthesizing ethyl 1-(oxiran-2-ylmethyl)-1H-pyrazole-5-carboxylates from easily accessible 3(5)-aryl- or methyl-1H-pyrazole-5(3)-carboxylates. Obtained intermediates were further treated with amines resulting in oxirane ring-opening and direct cyclisation—yielding target pyrazolo[1,5-a][1,4]diazepin-4-ones. A straightforward two-step synthetic approach was applied to expand the current study and successfully functionalize ethyl 1H-indole- and ethyl 1H-benzo[d]imidazole-2-carboxylates. The structures of fused heterocyclic compounds were confirmed by 1H, 13C, and 15N-NMR spectroscopy and HRMS investigation.

  介绍了合成四氢-4H-吡唑并[1,5-a][1,4]二氮杂卓-4-酮、四氢[1,4]二氮杂卓[1,2-a]吲哚-1-酮和四氢-1H-苯并[4,5]咪唑并[1,2-a][1,4]二氮杂卓-1-酮衍生物的一般方法。研究人员开发了一种区域选择性策略，从易于获得的 3(5)-芳基-或甲基-1H-吡唑-5(3)-羧酸乙酯合成 1-(环氧乙烷-2-基甲基)-1H-吡唑-5-羧酸乙酯。得到的中间体进一步用胺处理，导致环氧乙烷开环和直接环化，产生目标吡唑并[1,5-a][1,4]二氮杂卓-4-酮。目前的研究采用了简单的两步合成法，并成功地将 1H-indole- 乙酯和 1H-苯并[d]咪唑-2-甲酸乙酯功能化。融合杂环化合物的结构通过 1H、13C 和 15N-NMR 光谱以及 HRMS 调查得到了证实。