1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine | 817160-17-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
• 英文别名: 3-methoxy-1-(4-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine；3-methoxy-1-(4-nitrophenyl)sulfonyl-3,5-dihydro-2H-4,1-benzoxazepine
• CAS: 817160-17-1
• 化学式: C₁₆H₁₆N₂O₆S
• 分子量: 364.379
• InChiKey: GFZOLYGGBFYTCP-UHFFFAOYSA-N

物化性质

• 熔点：
  171.8-172.6 °C
• 沸点：
  549.7±60.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine 在 potassium carbonate 、 苯硫酚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以90%的产率得到(RS)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
  参考文献：
  名称：

  Synthesis of tetrahydrobenzoxazepine acetals with electron-withdrawing groups on the nitrogen atom. Novel scaffolds endowed with anticancer activity against breast cancer cells

  摘要：

  Synthetic approaches that have led to (RS)-3-methoxy-N-substituded-1,2,3,5-tetrahydro-4,1-benzoxazepines with different electron-withdrawing groups, and (RS)-2-methoxy-N-trifluoroacetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine are described. These novel synthons that were designed to be used as scaffolds for the preparation of new 0,N-acetals as anticancer agents, unexpectedly proved to show antiproliferative activity against the MCF-7 breast cancer cell line. It has been found that substituents on the nitrogen atom have an influence on biological activity. In particular, the presence of a trifluoroacetyl moiety on the nitrogen atom leads to amides displaying interesting in vitro antitumour activities. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.09.072
• 作为产物：
  描述：

  2-(((tert-butyldimethylsilyl)oxy)methyl)aniline 在 偶氮二甲酸二异丙酯 、 TEA 、 四丁基氟化铵 、 对甲苯磺酸 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 27.0h， 生成 1-(4-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
  参考文献：
  名称：

  Synthesis of tetrahydrobenzoxazepine acetals with electron-withdrawing groups on the nitrogen atom. Novel scaffolds endowed with anticancer activity against breast cancer cells

  摘要：

  Synthetic approaches that have led to (RS)-3-methoxy-N-substituded-1,2,3,5-tetrahydro-4,1-benzoxazepines with different electron-withdrawing groups, and (RS)-2-methoxy-N-trifluoroacetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine are described. These novel synthons that were designed to be used as scaffolds for the preparation of new 0,N-acetals as anticancer agents, unexpectedly proved to show antiproliferative activity against the MCF-7 breast cancer cell line. It has been found that substituents on the nitrogen atom have an influence on biological activity. In particular, the presence of a trifluoroacetyl moiety on the nitrogen atom leads to amides displaying interesting in vitro antitumour activities. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.09.072

文献信息

• Study of the Factors that Control the Ratio of the Products between 5-Fluorouracil, Uracil, and Tetrahydrobenzoxazepine <i>O</i>,<i>O</i>-Acetals Bearing Electron-Withdrawing Groups on the Nitrogen Atom
  作者：Mónica Díaz-Gavilán、José A. Gómez-Vidal、Antonio Entrena、Miguel A. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1021/jo052167m

  日期：2006.2.1

  derivatives for the Lewis acid mediated condensation reaction with pyrimidine bases to give O,N-acetals. Acetonitrile, stannic chloride, 50 °C, and a reaction time higher than 48 h are the optimum conditions for such condensation reactions. Under these conditions, 5-fluorouracil preferably links to the aminalic carbon through its N-1‘ ‘ position, while the attachment of the uracil fragment is through N-3‘ ‘

  （RS）-1-（2-硝基苯磺酰基）-和（RS）-1-（4-硝基苯磺酰基）-3-甲氧基-1,2,3,5-四氢-4,1-苯并x庚因是比1-更好的底物酰基-3-甲氧基-1,2,3,5-四氢-4,1-苯并x并庚因衍生物，在路易斯酸介导的与嘧啶碱的缩合反应中生成O，N-乙缩醛。乙腈，氯化锡，50°C和高于48小时的反应时间是此类缩合反应的最佳条件。在这些条件下，5-氟尿嘧啶优选通过其N -1''位置连接至氨基碳，而尿嘧啶片段的连接通过N -3''或N-1''分别为环状或非环状产物。分析和讨论了影响反应过程的原因。所述的检查1核磁共振光谱揭示了单一形式的存在下，仲胺11和两种构象异构体的叔磺酰胺7a中，b，图9a，b，和图10b以及用于酰胺7D和13，具有以下的分布：7a，59/41; 7b，53/47；9a，52/48；9b，59/41; 10b，56/44；7d，50/50; 13，80/20。随着温度的升高，7b的1
• Design, synthesis, HER2 inhibition and anticancer evaluation of new substituted 1,5-dihydro-4,1-benzoxazepines
  作者：Olga Cruz-López、Matilde Ner、Francho Nerín-Fonz、Yaiza Jiménez-Martínez、David Araripe、Juan A. Marchal、Houria Boulaiz、Hugo Gutiérrez-de-Terán、Joaquín M. Campos、Ana Conejo-García

  DOI：10.1080/14756366.2021.1948841

  日期：2021.1.1

  benzotriazole bioisosteric analogue, and the introduction of a bulky substituent at position 6 of the purine, on the biological effects. Their inhibition against isolated HER2 was studied and the structure–activity relationships have been confirmed by molecular modelling studies. The most potent compound against isolated HER2 is 9a with an IC50 of 7.31 µM. We have investigated the effects of the target compounds

  摘要 合成了一系列 11 种新的取代的 1,5-二氢-4,1-苯并恶氮衍生物，以研究 1-(苯磺酰基) 部分中甲基的影响、苯并三唑生物等排类似物取代嘌呤的影响，以及在嘌呤的 6 位引入庞大的取代基，对生物效应的影响。研究了它们对分离的 HER2 的抑制作用，分子模型研究证实了结构-活性关系。对孤立的 HER2 最有效的化合物是9a，IC 50为 7.31 µM。我们研究了目标化合物对细胞增殖的影响。对所有研究的肿瘤细胞系（IC 50）最具活性的化合物（7c） 0.42–0.86 µM) 不会对 pro-caspase 3 的表达产生任何改变，但会增加 caspase 1 的表达，并促进细胞焦亡。
• Synthesis and reactivity of (RS)-6-chloro-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)-7H- or 9H-purines bearing a nitrobenzenesulfonyl group on the nitrogen atom
  作者：Mónica Díaz-Gavilán、Duane Choquesillo-Lazarte、Josefa M. González-Pérez、Miguel A. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1016/j.tet.2007.03.155

  日期：2007.6

  acid-mediated condensation with 6-chloropurine. 6-Chloropurine leads to the N-7″ aminalic bond in the cyclic products and mainly to the N-9″ aminalic bond in the acyclic ones. Substitution of the chlorine atom at the 6″ position of the purine moiety is more feasible when the ring is alkylated at N-7″ than at N-9″. Exchange with a hydroxyl group is performed with water traces in deuterated dimethylsulfoxide

  的Ô，Ô -acetalic化合物（RS）-3-甲氧基-1 - [（2） -或（4）-nitrobenzenesulfonyl）] - 1,2,3,5-四氢-4,1-苯并氧氮杂已经研究了在路易斯酸介导的与6-氯嘌呤的缩合反应。6-氯嘌呤在环状产物中导致N -7“氨基键，而在非环状产物中主要导致N -9”氨基键。在6的氯原子的取代“当环被烷基化的嘌呤部分的位置是更可行Ñ比-7” Ñ-9”。在室温下，在溶剂介导的过程中，在氘代二甲基亚砜中与痕量水进行羟基交换。与强亲核试剂（例如，苯硫酚）的交换不需要进一步激活。
• New (RS)-benzoxazepin-purines with antitumour activity: The chiral switch from (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine
  作者：Luisa C. López-Cara、Ana Conejo-García、Juan A. Marchal、Giuseppe Macchione、Olga Cruz-López、Houria Boulaiz、María A. García、Fernando Rodríguez-Serrano、Alberto Ramírez、Carlos Cativiela、Ana I. Jiménez、Juan M. García-Ruiz、Duane Choquesillo-Lazarte、Antonia Aránega、Joaquín M. Campos

  DOI：10.1016/j.ejmech.2010.11.011

  日期：2011.1

  Completing an SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines has been prepared under microwave-assisted conditions. Their antiproliferative activities on MCF-7 and MDA-MB-231 cancerous cell lines are presented, being the majority of the IC50 values below 1 mu M. The most active compound (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1- benzoxazepin-3-yl]-9H-purine (14) presents an IC50 of 0.166 mu M against the human cancerous cell line MDA-MB-231. Compound 14 was the most selective against the human breast adenocarcinoma MCF-7 and MDA-MB-231 cancer cell lines (Therapeutic Indexes, TIs = 5.1 and 11.0, respectively) in relation to the normal one MCF-10A. (RS)-14 was resolved into its enantiomers. Both enantiomers are equally potent, but more potent than the corresponding racemic mixture. (R)-14 induces apoptosis against MCF-7 up to 52.50% of cell population after 48 h, being more potent than the clinical-used drug paclitaxel (43%). (RS)-14 induces no acute toxicity in mice after two weeks of treatment. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Synthesis of tetrahydrobenzoxazepine acetals with electron-withdrawing groups on the nitrogen atom. Novel scaffolds endowed with anticancer activity against breast cancer cells
  作者：Mónica Díaz-Gavilán、Fernando Rodríguez-Serrano、José A. Gómez-Vidal、Juan A. Marchal、Antonia Aránega、Miguel Á. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1016/j.tet.2004.09.072

  日期：2004.12

  Synthetic approaches that have led to (RS)-3-methoxy-N-substituded-1,2,3,5-tetrahydro-4,1-benzoxazepines with different electron-withdrawing groups, and (RS)-2-methoxy-N-trifluoroacetyl-2,3,4,5-tetrahydro-1,4-benzoxazepine are described. These novel synthons that were designed to be used as scaffolds for the preparation of new 0,N-acetals as anticancer agents, unexpectedly proved to show antiproliferative activity against the MCF-7 breast cancer cell line. It has been found that substituents on the nitrogen atom have an influence on biological activity. In particular, the presence of a trifluoroacetyl moiety on the nitrogen atom leads to amides displaying interesting in vitro antitumour activities. (C) 2004 Elsevier Ltd. All rights reserved.