1,3-dibenzyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione | 951326-70-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1,3-dibenzyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
• 英文别名: (3S)-1,3-dibenzyl-3,4-dihydro-1,4-benzodiazepine-2,5-dione
• CAS: 951326-70-8
• 化学式: C₂₃H₂₀N₂O₂
• 分子量: 356.424
• InChiKey: NXEAZDQUXPQNGE-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,3-dibenzyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione 、 3-溴丙烯 在 aluminum oxide 、 potassium fluoride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 48.0h， 以97%的产率得到(S)-4-allyl-1,3-dibenzyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 1,4-benzodiazepine-2,5-dione-based HDAC inhibitors

  摘要：

  New histone deacetylase inhibitors have been synthesized and evaluated for their activity against non-small lung cancer cell line H661. These compounds have been designed with diversely substituted 1,4-benzodiazepine-2,5-dione moieties as cyclic peptide mimic cap structures, and a hydroxamate side chain. Biological evaluations demonstrated that benzodiazepine-based HDACi bearing an aromatic substituent at the N1 position exhibited promising anti proliferative and HDAC-inhibitory activities. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.06.067
• 作为产物：
  描述：

  在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 以52%的产率得到1,3-dibenzyl-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione
  参考文献：
  名称：

  A Novel Solid-Phase Synthetic Method for 1,4-Benzodiazepine-2,5-dione Derivatives

  摘要：

  利用与聚合物结合的蒽酸衍生物 1，我们通过前所未有的反应序列，即还原烷基化-N-保护性氨基酸偶联-保护性环化反应，得到了 1,4-苯并二氮杂卓-2,5-二酮衍生物 3（R3 = H，R4 = H，MeO，Cl），五步法的总分离产率为 28-71%，纯度为 95-99%。对树脂 2 采用新方案，可获得 7-苯甲酰胺基-1,4-苯并二氮杂卓-2,5-二酮衍生物 3（R1 = Bn，R4 = 7-BzNH），其在 AMEBA 树脂 7 中的七步或八步分离收率为 19-42%，纯度为 92-98%。

  DOI：

  10.1055/s-2008-1078484

文献信息

• The 1,4-Benzodiazepine-2,5-dione Small Molecule Template Results in Melanocortin Receptor Agonists with Nanomolar Potencies
  作者：Christine G. Joseph、Krista R. Wilson、Michael S. Wood、Nicholas B. Sorenson、Dong V. Phan、Zhimin Xiang、Rachel M. Witek、Carrie Haskell-Luevano

  DOI：10.1021/jm701303z

  日期：2008.3.13

  The melanocortin system consists of five seven-transmembrane spanning G-protein coupled receptors (MC1-5) that are stimulated by endogenous agonists and antagonized by the only two known endogenous antagonists of GPCRs, agouti and agouti-related protein (AGRP). These receptors have been associated with many physiological functions, including the involvement of the MC4R in feeding behavior and energy homeostasis, making this system an attractive target for the treatment of obesity. Small-molecule mimetics of endogenous ligands may result in the development of compounds with properties more suitable for use as therapeutic agents. The research presented herein involves the synthesis and analysis of 12 melanocortin receptor agonists using the 1,4-benzodiazepine-2,5-dione template and is the first report of these derivatives as melanocortin receptor agonists. Structure-activity relationship studies using this privileged structure, template has resulted in molecules with molecular weights around 400 that possess nanomolar agonist potency at the melanocortin receptors examined in this study.
• Design, synthesis and biological evaluation of 1,4-benzodiazepine-2,5-dione-based HDAC inhibitors
  作者：Lynda Loudni、Joëlle Roche、Vincent Potiron、Jonathan Clarhaut、Christian Bachmann、Jean-Pierre Gesson、Isabelle Tranoy-Opalinski

  DOI：10.1016/j.bmcl.2007.06.067

  日期：2007.9

  New histone deacetylase inhibitors have been synthesized and evaluated for their activity against non-small lung cancer cell line H661. These compounds have been designed with diversely substituted 1,4-benzodiazepine-2,5-dione moieties as cyclic peptide mimic cap structures, and a hydroxamate side chain. Biological evaluations demonstrated that benzodiazepine-based HDACi bearing an aromatic substituent at the N1 position exhibited promising anti proliferative and HDAC-inhibitory activities. (c) 2007 Elsevier Ltd. All rights reserved.
• A Novel Solid-Phase Synthetic Method for 1,4-Benzodiazepine-2,5-dione Derivatives
  作者：Moon-Kook Jeon、Jeong-Jin Kwon、Myung-Su Kim、Young-Dae Gong

  DOI：10.1055/s-2008-1078484

  日期：——

  Utilizing polymer-bound anthranilic acid derivatives 1, we were able to obtain the 1,4-benzodiazepine-2,5-dione derivatives 3 (R3 = H, R4 = H, MeO, Cl) through an unprecedented reaction sequence, reductive alkylation-N-protected amino acid coupling-deprotective cyclization, in 28-71% five-step overall isolated yields and 95-99% purities from Wang resin 4. Applying the novel protocol to the resin 2, the 7-benzamido-1,4-benzodiazepine-2,5-dione derivatives 3 (R1 = Bn, R4 = 7-BzNH) could be obtained in 19-42% seven- or eight-step overall isolated yields and 92-98% purities from AMEBA resin 7.

  利用与聚合物结合的蒽酸衍生物 1，我们通过前所未有的反应序列，即还原烷基化-N-保护性氨基酸偶联-保护性环化反应，得到了 1,4-苯并二氮杂卓-2,5-二酮衍生物 3（R3 = H，R4 = H，MeO，Cl），五步法的总分离产率为 28-71%，纯度为 95-99%。对树脂 2 采用新方案，可获得 7-苯甲酰胺基-1,4-苯并二氮杂卓-2,5-二酮衍生物 3（R1 = Bn，R4 = 7-BzNH），其在 AMEBA 树脂 7 中的七步或八步分离收率为 19-42%，纯度为 92-98%。