8-methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one | 93533-11-0

• 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: 8-methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
• 英文别名: 8-methoxy-5,10-dihydro-11H-dibenzo[b,e][1,4]diazepin-11-one；2-methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one；8-methoxy-5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-one；3-methoxy-5,11-dihydrobenzo[b][1,4]benzodiazepin-6-one
• CAS: 93533-11-0
• 化学式: C₁₄H₁₂N₂O₂
• 分子量: 240.261
• InChiKey: SCBSGIDQOXINQM-UHFFFAOYSA-N

物化性质

• 熔点：
  203-206 °C
• 沸点：
  348.5±41.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 3.0h， 生成 11-Chloro-8-methoxy-5H-dibenzo[b,e][1,4]diazepine
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Triflate-Substituted Analogues of Clozapine:  Identification of a Novel Atypical Neuroleptic

  摘要：

  The trifluoromethanesulonyloxy (TfO) analogues 3 and 4 of 8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine (clozapine, 1) and its 2-chloro isomer (iso-clozapine, 2), respectively, were synthesized via their OMe and OH analogues with the conventional synthetic method of the tricyclic dibenzodiazepines and evaluated pharmacologically along with their parent drugs. The binding profile of the 2-OTf analogue (4) is comparable to the binding profile of 1, although the affinity for the dopamine (DA) D-2 receptors is higher (IC50 values are 31 nM and 330 nM for compounds 4 and 1, respectively). Interestingly, no notable affinity for muscarinic receptors could be detected in compound 4. On the contrary, the 3-OTf analogue 3 only displayed affinity for muscarinic M-1 receptors (IC50 value 35 nM) and no affinity (IC50 value > 500 nM) for the other receptors tested. The 10 mu mol/kg sc dose, but nod the 10 mu mol/kg po dose, of compound 4 stimulated the output of DA, Increases of 80% and 35% in DOPAC output from the dorsal striatum were seen after sc and po administrations of 10 mu mol/kg of compound 4, respectively. Doses up to 100 mu mol/kg of compound 3 had no effect on either parameter. Doses up to 100 mu mol/kg of compound 4 were not cataleptogenic, but significantly decreased apomorphine-induced locomotor activity. In conclusion, compound 4 (GMC1-169) is a new clozapine-like neuroleptic candidate, which is lacking anticholinergic properties and displays a higher potency, as compared to clozapine (1) itself.

  DOI：

  10.1021/jm9704457
• 作为产物：
  描述：

  4-甲氧基-2-硝基乙酰苯胺 在 盐酸 、 4-二甲氨基吡啶 、 copper(l) iodide 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 tin(ll) chloride 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.25h， 生成 8-methoxy-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one
  参考文献：
  名称：

  Design, Synthesis and Anticancer Activity Evaluation of Diazepinomicin Derivatives

  摘要：

  合成了一系列地西泮米辛衍生物，并在体外评估了其对人类癌瘤细胞系的生长抑制活性。结果表明这种化合物具有抗癌选择性。根据结果，讨论了初步的结构-活性关系。

  DOI：

  10.2174/1570180811310040011

文献信息

• Concise Palladium-Catalyzed Synthesis of Dibenzodiazepines and Structural Analogues
  作者：Dmitry Tsvelikhovsky、Stephen L. Buchwald

  DOI：10.1021/ja206229y

  日期：2011.9.14

  A general and highly efficient protocol for the synthesis of dibenzodiazepines and their structural analogues is reported. In the presence of catalytic quantities of palladium, readily accessible precursors are cross-coupled with ammonia and then spontaneously undergo an intramolecular condensation to form the corresponding dibenzodiazepines in one step. This new strategy is applicable to the construction

  报告了合成二苯二氮卓类及其结构类似物的通用且高效的方案。在催化量的钯存在下，容易获得的前体与氨交叉偶联，然后自发地进行分子内缩合，一步形成相应的二苯二氮卓类。这种新策略适用于构建各种二苯并氧氮杂和其他结构相关的杂环。
• Antiproliferative and Differentiating Activities of a Novel Series of Histone Deacetylase Inhibitors
  作者：Monica Binaschi、Andrea Boldetti、Maurizio Gianni、Carlo Alberto Maggi、Martina Gensini、Mario Bigioni、Massimo Parlani、Alessandro Giolitti、Maddalena Fratelli、Claudia Valli、Mineko Terao、Enrico Garattini

  DOI：10.1021/ml1001163

  日期：2010.11.11

  Histone deacetylases are promising molecular targets for the development of antitumor agents. A novel series of histone deacetylase inhibitors of the hydroxamic acid type were synthesized for structure-activity studies. Thirteen tricyclic dibenzo-diazepine, -oxazepine, and -thiazepine analogues were studied and shown to induce variable degrees of histone H3/H4 and tubulin acetylation in a cellular

  组蛋白脱乙酰基酶是开发抗肿瘤剂的有希望的分子靶标。合成了一系列新的异羟肟酸类型的组蛋白脱乙酰基酶抑制剂用于结构活性研究。研究了十三种三环二苯并二氮杂卓，-奥氮平和-硫氮平类似物，并显示在对全反式视黄酸（ATRA）敏感的骨髓性白血病细胞模型中，可诱导不同程度的组蛋白H3 / H4和微管蛋白乙酰化。进行了三种底物的乙酰化，肿瘤细胞生长抑制和ATRA依赖性细胞分化之间的多参数关联，提供了控制这些活性的化学功能的信息。对于两种类似物，证明了在动物中的抗肿瘤活性。
• Reductive Condensation of a Nitro Group with Carboxylic Acids Promoted by Phosphorus(III) Compounds: A Short Route to 5H-Dibenzo[b,e][1,4]diazepin-11(10H)-ones
  作者：Zbigniew Wróbel、Michał Tryniszewski、Robert Bujok、Roman Gańczarczyk

  DOI：10.1055/s-0040-1707347

  日期：——

  Abstract Tributyl- or triphenylphosphine promotes a one-pot, three-step method for the synthesis of differently substituted dibenzodiazepinones from N-aryl-2-nitroanilines. Pyridine analogues and the corresponding thiazepinones can also be formed using this method. The process involves deoxygenation of the nitro group, then formation of an iminophosphorane intermediate and its intramolecular condensation

  摘要 三丁基或三苯基膦促进了一锅三步法，从N-芳基-2-硝基苯胺合成不同取代的二苯并二氮杂酮。吡啶类似物和相应的噻嗪酮也可以使用这种方法形成。该方法包括使硝基脱氧，然后形成亚氨基磷烷中间体，以及其与置于N-芳基中的羧基的分子内缩合。讨论了羧基在亚氨基磷烷的形成中的作用和环化方式。
• Synthesis and biological evaluation of BU-4664L derivatives as potential anticancer agents
  作者：Chao Liu、Yuan-Yuan Xu、Zhao-Hui Wen、Yue-Hui Dong、Zhao-Peng Liu

  DOI：10.1016/j.bmcl.2021.128474

  日期：2022.1

  BU-4664L is a naturally occurring N-farnesylated dibenzodiazepinone with important biological activities. Herein, we report the synthesis and antitumor evaluation of two series of BU-4664L derivatives bearing different substituent patterns on the dibenzodiazepinone core and with diverse side chains. All of the derivatives displayed micromolar activity against the human prostate cancer PC-3 cells, while

  BU-4664L 是一种天然存在的N-法尼基化二苯并二氮杂卓，具有重要的生物活性。在此，我们报告了在二苯并二氮杂酮核心上具有不同取代基模式并具有不同侧链的两个系列 BU-4664L 衍生物的合成和抗肿瘤评估。所有的衍生物都对人前列腺癌 PC-3 细胞表现出微摩尔活性，而对人肺 H460 细胞的活性较低或没有活性。最具活性的衍生物是10a和16c，它们对 PC-3 细胞具有抗增殖活性，GI 50值分别为 5.66 和 5.94 μM，因此代表了有希望进一步开发的先导化合物。