tert-butyl (S)-(4-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyl)carbamate | 939784-02-8

• 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: tert-butyl (S)-(4-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyl)carbamate
• 英文别名: tert-butyl N-[4-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]butyl]carbamate
• CAS: 939784-02-8
• 化学式: C₂₄H₂₉N₃O₃
• 分子量: 407.513
• InChiKey: HROQLEWKASEJJL-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(4-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyl)carbamate 在 caesium carbonate 作用下， 以 二氯甲烷 为溶剂， 生成 [4-[[(3S)-3-(4-aminobutyl)-2-oxo-5-phenyl-3H-1,4-benzodiazepin-1-yl]methyl]phenyl] dihydrogen phosphate;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines

  摘要：

  Novel 1,4-benzodiazepine compounds were synthesized and evaluated for their ability to inhibit the proliferation of tumor cells. Some compounds revealed activities in the micromolar range and were more efficient than reference compound Ro 5-4864. Preliminary SAR helped to identify critical motifs for antiproliferative activity and led to the discovery of a compound selective for a melanoma cell line, known for its resistance to chemotherapy. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.016
• 作为产物：
  描述：

  2-氨基二苯甲酮 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 、 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 tert-butyl (S)-(4-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)butyl)carbamate
  参考文献：
  名称：

  Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines

  摘要：

  Novel 1,4-benzodiazepine compounds were synthesized and evaluated for their ability to inhibit the proliferation of tumor cells. Some compounds revealed activities in the micromolar range and were more efficient than reference compound Ro 5-4864. Preliminary SAR helped to identify critical motifs for antiproliferative activity and led to the discovery of a compound selective for a melanoma cell line, known for its resistance to chemotherapy. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.016

文献信息

• Design and synthesis of benzodiazepine analogs as isoform-selective human lysine deacetylase inhibitors
  作者：D. Rajasekhar Reddy、Flavio Ballante、Nancy J. Zhou、Garland R. Marshall

  DOI：10.1016/j.ejmech.2016.12.032

  日期：2017.2

  comprehensive investigation was performed to identify new benzodiazepine (BZD) derivatives as potent and selective human lysine deacetylase inhibitors (hKDACis). A total of 108 BZD compounds were designed, synthesized and from that 104 compounds were biologically evaluated against human lysine deacetylases (hKDACs) 1, 3 and 8 (class I) and 6 (class IIb). The most active compounds showed mid-nanomolar potencies

  进行了全面的调查，以确定新的苯二氮卓（BZD）衍生物作为有效的和选择性的人赖氨酸脱乙酰基酶抑制剂（hKDACis）。总共设计，合成了108种BZD化合物，并从这104种化合物中分别针对人赖氨酸脱乙酰基酶（hKDAC）1、3和8（I类）和6（IIb类）进行了生物学评估。活性最高的化合物对hKDACs 1、3和6表现出中等纳摩尔效价，对hKDAC8的微摩尔活性，而一种有前途的化合物（6q）显示出在不同酶同工型中对hKDAC3的选择性。生成了hKDAC6同源性模型，该模型通过分子动力学模拟进行了改进，并进行了分子对接研究，以使主要的配体-残基相互作用合理化，并定义了结构-活性-关系。实验结果证实了在追求hKDAC同工型选择性抑制时，苯并二氮杂moiety部分作为封端基是有用的，这表明在设计新的hKDACis时可以继续使用。