(RS)-2,6-dichloro-9-[1-(o-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine | 1207993-84-7

• 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)-2,6-dichloro-9-[1-(o-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine
• 英文别名: 3-(2,6-dichloropurin-9-yl)-1-(2-nitrophenyl)sulfonyl-3,5-dihydro-2H-4,1-benzoxazepine
• CAS: 1207993-84-7
• 化学式: C₂₀H₁₄Cl₂N₆O₅S
• 分子量: 521.34
• InChiKey: UYKGSVJABNEMHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  144
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (RS)-2,6-dichloro-9-[1-(o-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine 在 三氟乙酸 、 sodium iodide 作用下， 反应 6.0h， 以66%的产率得到(RS)-2-chloro-6-iodo-9-[1-(o-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2010.11.011
• 作为产物：
  描述：

  2,6-二氯嘌呤 、 1-(2-nitrobenzenesulfonyl)-3-methoxy-1,2,3,5-tetrahydro-4,1-benzoxazepine 在 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 为溶剂， 反应 0.08h， 以29%的产率得到1-[(o-nitrophenyl)sulfonyl]-1,5-dihydro-4,1-benzoxazepin
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2010.11.011

文献信息

• 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。
• [EN] NOVEL (RS)-7- OR 9-(1,2,3,5-TETRAHYDRO-4,1-BENZOXAZEPIN-3-IL)-7H OR 9H-PURINES HAVING ANTITUMOUR ACTIVITY<br/>[ES] NUEVAS (RS)-7- Ó 9-(1,2,3,5-TETRAHIDRO-4,1-BENZOXAZEPIN-3-IL)-7H Ó 9H-PURINAS CON ACTIVIDAD ANTITUMORAL<br/>[FR] NOUVELLES (RS)-7- OU 9-(1,2,3,5-TÉTRAHYDRO-4,1-BENZOXAZÉPIN-3-YL)-7H OU 9H-PURINES À ACTIVITÉ ANTITUMORALE
  申请人：UNIV GRANADA

  公开号：WO2010018268A1

  公开（公告）日：2010-02-18

  La invención proporciona compuestos que encuentran aplicación en el tratamiento de tumores en animales y seres humanos. Los resultados experimentales obtenidos sobre líneas celulares tumorales y no tumorales de mama sugieren que los compuestos seleccionados poseen una actividad antitumoral específica y selectiva, convirtiéndose en excelentes candidatos para una futura aplicación en el tratamiento de diversos tipos de cánceres.
• 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.