(6-oxo-5,11-dihydro-6H-dibenzazepin-11-yl)methylamine | 141528-84-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (6-oxo-5,11-dihydro-6H-dibenzazepin-11-yl)methylamine
• 英文别名: 11-(aminomethyl)-5,11-dihydrobenzo[c][1]benzazepin-6-one
• CAS: 141528-84-9
• 化学式: C₁₅H₁₄N₂O
• 分子量: 238.289
• InChiKey: UJYSNYBSRZPNDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  18.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  55.12
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (6-oxo-5,11-dihydro-6H-dibenzazepin-11-yl)methylamine 、 1-[9-Prop-2-enyl-6-(prop-2-enylamino)purin-2-yl]piperidin-4-one 在 三乙酰氧基硼氢化钠 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以64.1%的产率得到11-[[[1-[9-Prop-2-enyl-6-(prop-2-enylamino)purin-2-yl]piperidin-4-yl]amino]methyl]-5,11-dihydrobenzo[c][1]benzazepin-6-one
  参考文献：
  名称：

  New Purines and Purine Analogs as Modulators of Multidrug Resistance

  摘要：

  A series of 36 purine and purine analog derivatives have been synthesized and tested for their ability to modulate multidrug resistance in vitro (P388/VCR-20 and KB-A1 cells) and in vivo (P388/VCR leukemia). Compounds were compared to S9788, a triazine derivative which has already shown some activity during phase 1 clinical trials and also a limiting cardiovascular side effect possibly linked to its calcium channel affinity. The fact that active compounds increase adriamycin accumulation in the resistant KB-A1 cells, and not in the sensitive KB-3-1 cells, suggests they act predominantly by inhibiting the P-glycoprotein-catalyzed efflux of cytotoxic agents. No direct relation was found between the affinity for the phenylalkylamine binding site of the calcium channel and in vitro sensitization of resistant cells. In vivo, when administered po in association with vincristine (0.25 mg/kg), five compounds (3, 4, 9, 25, and 26), of very differing calcium channel affinities (K-i from 5 to 560 nM), fully restored (T/V greater than or equal to 1.4) the sensitivity of P388/VCR leukemia to vincristine.

  DOI：

  10.1021/jm960361i
• 作为产物：
  描述：

  5H-二苯并[b,e]氮杂卓-6,11-二酮 在 sodium tetrahydroborate 、 氯化亚砜 、 氨 、 氢气 、 镍 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 60.0~80.0 ℃ 、6.08 MPa 条件下， 反应 6.5h， 生成 (6-oxo-5,11-dihydro-6H-dibenzazepin-11-yl)methylamine
  参考文献：
  名称：

  New triazine derivatives as potent modulators of multidrug resistance

  摘要：

  A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity. Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5-mu-M in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin. The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators. In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the TIC by 39% in mice bearing the resistant tumor cell line P388/VCR. According to these interesting properties, 16 was selected for a clinical development because it was more bioavailable than 34, even though it was less active.

  DOI：

  10.1021/jm00091a017