benzyl N-[1-(2-hydroxyethyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamate | 153826-05-2

• 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: benzyl N-[1-(2-hydroxyethyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamate
• CAS: 153826-05-2
• 化学式: C₂₅H₂₃N₃O₄
• 分子量: 429.475
• InChiKey: ZLTJPOXBSZYJED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  91.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl N-[1-(2-hydroxyethyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamate 在 4-二甲氨基吡啶 、 palladium 10% on activated carbon 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 生成 N-[2-oxo-1-(2-oxoethyl)-5-phenyl-3H-1,4-benzodiazepin-3-yl]-2-phenylacetamide
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors

  摘要：

  As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction, SUMO-specific proteases (SENPs) reversibly remove SUMO from the SUMOylated proteins. Recently, SENP1 was found to be a potential therapeutic target for the treatment of prostate cancers, but the design and synthesis of its inhibitors have not been reported. We designed and synthesized a series of benzodiazepine-based SENP1 inhibitors, and they showed inhibitory activity as good as IC(50) = 9.2 mu M (compound 38). The structure-activity relationship was also discussed. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.101
• 作为产物：
  描述：

  benzyl N-[[(2-benzoylphenyl)carbamoyl](1H-1,2,3-benzotriazol-1-yl)methyl]carbamate 在 氨 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 3.0h， 生成 benzyl N-[1-(2-hydroxyethyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]carbamate
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors

  摘要：

  As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction, SUMO-specific proteases (SENPs) reversibly remove SUMO from the SUMOylated proteins. Recently, SENP1 was found to be a potential therapeutic target for the treatment of prostate cancers, but the design and synthesis of its inhibitors have not been reported. We designed and synthesized a series of benzodiazepine-based SENP1 inhibitors, and they showed inhibitory activity as good as IC(50) = 9.2 mu M (compound 38). The structure-activity relationship was also discussed. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.101

文献信息

• Development of 1,4-benzodiazepine cholecystokinin type B antagonists
  作者：Mark G. Bock、Robert M. DiPardo、Ben E. Evans、Kenneth E. Rittle、Willie L. Whitter、Victor M. Garsky、Kevin F. Gilbert、James L. Leighton、Kenneth L. Carson

  DOI：10.1021/jm00078a018

  日期：1993.12

  4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by reasoned modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329, this paper chronicles the development of potent, orally effective compounds in which selectivity for the CCK-B receptor subtype was achieved. The principal lead structure that emerged from these studied is

  描述了一系列3-（芳基脲基）-5-苯基-1,4-苯并二氮杂卓，肽激素胆囊收缩素（CCK）的非肽拮抗剂。通过对CCK-A选择性3-甲酰胺基-1,4-苯并二氮杂卓MK-329的合理修饰而衍生，本文记载了有效的，口服有效的化合物的开发，其中对CCK-B受体亚型具有选择性。从这些研究中得出的主要铅结构是L-365,260，该化合物已提交临床评估。讨论了通过适当的结构修饰来调节这些苯并二氮杂the的受体相互作用的能力的细节，这暗示了进一步完善这类化合物的CCK-B受体亲和力和选择性的可能性。
• Design, synthesis, and biological evaluation of benzodiazepine-based SUMO-specific protease 1 inhibitors
  作者：Zhitao Qiao、Weiwei Wang、Lie Wang、Donghua Wen、Yaxue Zhao、Qing Wang、Qingqing Meng、Guoqiang Chen、Yingli Wu、Huchen Zhou

  DOI：10.1016/j.bmcl.2011.08.101

  日期：2011.11

  As the best-characterized ubiquitin-like protein (UBL), small ubiquitin-related modifier (SUMO) was found to conjugate with a number of proteins to regulate cellular functions including transcription, signal transduction, and cell cycle. While E1, E2 and E3 ligases are responsible for the forward SUMOylation reaction, SUMO-specific proteases (SENPs) reversibly remove SUMO from the SUMOylated proteins. Recently, SENP1 was found to be a potential therapeutic target for the treatment of prostate cancers, but the design and synthesis of its inhibitors have not been reported. We designed and synthesized a series of benzodiazepine-based SENP1 inhibitors, and they showed inhibitory activity as good as IC(50) = 9.2 mu M (compound 38). The structure-activity relationship was also discussed. (C) 2011 Elsevier Ltd. All rights reserved.