(RS)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine | 817160-18-2

• 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: (RS)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
• 英文别名: 3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine
• CAS: 817160-18-2
• 化学式: C₁₀H₁₃NO₂
• 分子量: 179.219
• InChiKey: WPQZYNPIMSVUCA-UHFFFAOYSA-N

物化性质

• 熔点：
  89.5-90.5 °C
• 沸点：
  315.7±42.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  30.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (RS)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine 在 吡啶 、 三甲基氯硅烷 、 四氯化锡 、 六甲基二硅氮烷 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 72.08h， 生成 6-chloro-9-[1-(p-methylbenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-9H-purine
  参考文献：
  名称：

  新型取代的 1,5-二氢-4,1-苯并恶氮杂的设计、合成、HER2 抑制和抗癌评估

  摘要：

  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。

  DOI：

  10.1080/14756366.2021.1948841
• 作为产物：
  描述：

  2-(((tert-butyldimethylsilyl)oxy)methyl)aniline 在 偶氮二甲酸二异丙酯 、 TEA 、 三氟化硼乙醚 、 四丁基氟化铵 、 potassium carbonate 、 苯硫酚 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 47.0h， 生成 (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

文献信息

• Anticancer activity of (1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-pyrimidines and -purines against the MCF-7 cell line: Preliminary cDNA microarray studies
  作者：Mónica Díaz-Gavilán、José A. Gómez-Vidal、Fernando Rodríguez-Serrano、Juan A. Marchal、Octavio Caba、Antonia Aránega、Miguel A. Gallo、Antonio Espinosa、Joaquín M. Campos

  DOI：10.1016/j.bmcl.2007.12.070

  日期：2008.2

  Completing a SAR study, a series of (RS)-1- or 3-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-pyrimidines and (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H- or 9H-purines have been prepared. Their antiproliferative activities on MCF-7 cells are here presented and discussed. (RS)-6-Chloro-9-[1-(9H-9-fluorenylmethoxycarbonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]-9H-purine (28) is the most active (IC50 = 0.67 +/- 0.18 mu M) of the series so far described. cDNA microarray technology reveals potential drug targets, which are mainly centred on apoptosis regulatory pathway genes. (c) 2008 Elsevier Ltd. 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.
• 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。