2,3-二氢-1,4-苯并二噁英-6-碳酰肼 | 98953-13-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 中文名称: 2,3-二氢-1,4-苯并二噁英-6-碳酰肼
• 英文名称: 2,3-dihydrobenzo[b][1,4]dioxine-6-carbohydrazide
• 英文别名: 2,3-Dihydro-1,4-benzodioxine-6-carbohydrazide
• CAS: 98953-13-0
• 化学式: C₉H₁₀N₂O₃
• mdl: MFCD01536451
• 分子量: 194.19
• InChiKey: YENPHHQNXHYBCE-UHFFFAOYSA-N

物化性质

• 熔点：
  141 °C(Solv: water (7732-18-5))
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  2,3-二氢-1,4-苯并二噁英-6-碳酰肼 在 sodium ethanolate 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-5-((2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)thio)-1,3,4-oxadiazole
  参考文献：
  名称：

  Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents

  摘要：

  A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 +/- 0.2, 30.0 +/- 1.2, 18.3 +/- 1.4 mu M, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 mu M, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 mu g/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.02.008
• 作为产物：
  描述：

  原儿茶酸 在 potassium carbonate 、 肼 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 72.25h， 生成 2,3-二氢-1,4-苯并二噁英-6-碳酰肼
  参考文献：
  名称：

  发现一系列含有哌嗪骨架作为潜在FAK抑制剂的1,3,4-恶二唑-2（3H）-硫酮衍生物。

  摘要：

  黏着斑激酶（FAK）是重要的药物靶标，在介导信号转导系统中起着基本作用。我们在此报告了一种新型的1,3,4-恶二唑-2（3H）-硫酮衍生物的发现，该衍生物含有哌嗪骨架，对FAK的效力增强。测试了所有17种新合成化合物对四种癌细胞HepG2，Hela，SW116和BGC823的抗癌活性。由于1，4-苯并二恶烷，1，3，4-恶二唑和哌嗪环的结合，它们大多数表现出显着的抗肿瘤活性。值得注意的是，化合物5m表现出最强的生物学活性（HepG2的IC50 =5.78μM，SW1116的IC50 =47.15μM），其抗FAK抑制活性（IC50 =0.78μM）也最好。

  DOI：

  10.1016/j.bmc.2017.03.038

文献信息

• Synthesis and antitumor activity of 1,3,4-oxadiazole possessing 1,4-benzodioxan moiety as a novel class of potent methionine aminopeptidase type II inhibitors
  作者：Juan Sun、Ming-Hui Li、Shao-Song Qian、Feng-Jiao Guo、Xiao-Fang Dang、Xiao-Ming Wang、Ya-Rong Xue、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2013.03.068

  日期：2013.5

  A series of 1,3,4-oxadiazole derivatives containing 1,4-benzodioxan moiety (7a–7q) have been designed, synthesized and evaluated for their antitumor activity. Most of the synthesized compounds were proved to have potent antitumor activity and low toxicity. Among them, compound 7a showed the most potent biological activity against Human Umbilical Vein Endothelial cells, which was comparable to the positive

  已设计，合成并评估了一系列含有1,4-苯并二恶烷部分（7a – 7q）的1,3,4-恶二唑衍生物的抗肿瘤活性。已证明大多数合成的化合物具有有效的抗肿瘤活性和低毒性。其中，化合物7a对人脐静脉内皮细胞表现出最强的生物学活性，与阳性对照相当。凋亡和流式细胞仪（FCM）的结果表明，化合物7a通过抑制MetAP2途径诱导细胞凋亡。进行分子对接以将化合物7a定位于MetAP2结合位点，以探索潜在的靶标。
• Triazole derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US06265426B1

  公开（公告）日：2001-07-24

  The present invention relates to triazole and imidazole derivatives of formula I and to their pharmaceutically acceptable acid addition salts. These compounds are NMDA receptor subtype blockers and are useful for the treatment of diseases related to the NMDA receptor.

  本发明涉及式I的三唑和咪唑衍生物及其药用可接受的酸盐。这些化合物是NMDA受体亚型阻滞剂，对治疗与NMDA受体相关的疾病有用。
• Synthesis and Antibacterial Activity of Cinnamaldehyde Acylhydrazone with a 1,4-Benzodioxan Fragment as a Novel Class of Potent β-Ketoacyl–Acyl Carrier Protein Synthase III (FabH) Inhibitor
  作者：Xiaoda Song、Yushun Yang、Jing Zhao、Yangjian Chen

  DOI：10.1248/cpb.c14-00485

  日期：——

  Fatty acid biosynthesis is essential for bacterial survival. β-Ketoacyl–acyl carrier protein (ACP) synthase III (FabH), is a particularly attractive antibacterial target, since it is central to the initiation of fatty acid biosynthesis. Three series of 21 cinnamaldehyde acylhydrazone derivatives, A3–9, B3–9, and C3–9, were synthesized and evaluated for FabH-inhibitory activity. Compound B6 showed the most potent biological activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis (minimum inhibitory concentrations (MICs) values: 1.56–3.13 µg/mL) and was comparable with the positive control. Docking simulation by positioning compound B6 in the FabH structure active site was performed to explore the possible binding model.

  脂肪酸生物合成对细菌的生存至关重要。β-酮酰基载体蛋白（ACP）合成酶III（FabH）因其在脂肪酸生物合成启动中的核心作用，是一个特别有吸引力的抗菌目标。合成了三系列共21种肉桂醛酰腙衍生物A3-9、B3-9和C3-9，并评估了它们对FabH的抑制活性。化合物B6显示出对大肠杆菌、绿脓杆菌、金黄色葡萄球菌和枯草芽孢杆菌最强的生物活性（最低抑制浓度（MICs）值为1.56-3.13 µg/mL），与阳性对照相当。通过将化合物B6定位在FabH结构活性位点的对接模拟，探索了可能的结合模型。
• Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase
  作者：Yu-Shun Yang、Qing-Shan Li、Shuai Sun、Yan-Bin Zhang、Xiao-Liang Wang、Fei Zhang、Jian-Feng Tang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.08.043

  日期：2012.10

  Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1–C15 and D1–D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-RafV600E

  合成了两个系列的新型含2,3-二氢苯并[ b ] [1,4]二恶英的4,5-二氢-1 H-吡唑衍生物C1 - C15和D1 - D15，并评估了它们对B-Raf的抑制作用和防扩散活动。化合物C14（（3-（4-溴苯基）-5-（2-氟苯基）-4,5-二氢-1 H-吡唑-1-基）（2,3-二氢苯并[ b ] [1,4]二恶英-6-yl）methanone）对B-Raf V600E（IC 50  = 0.11μM）和WM266.4人黑素瘤细胞系（GI 50 = 0.58μM），与阳性对照厄洛替尼相当，并且比我们以前最好的化合物更有效，而D10（（2,3-dihydrobenzo [ b ] [1,4] dioxin-2-yl）（5-（3-氟苯基）-3-苯基-4,5-二氢-1 H-吡唑-1-基）甲酮在D系列中表现最好（IC 50  = 1.70μM; GI 50  = 1.45μM）。进行了对接模
• Synthesis and antitumor activity of 1,2,4-triazoles having 1,4-benzodioxan fragment as a novel class of potent methionine aminopeptidase type II inhibitors
  作者：Ya-Ping Hou、Juan Sun、Zhong-Hua Pang、Peng-Cheng Lv、Dong-Dong Li、Li Yan、Hong-Jia Zhang、Emily Xi Zheng、Jing Zhao、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2011.08.063

  日期：2011.10

  A series of 1,2,4-triazole derivatives containing 1,4-benzodioxan (5a–5q) have been designed, synthesized, structurally determined, and their biological activities were evaluated as potential MetAP2 inhibitors. All the synthesized compounds were first reported. Among the compounds, compound 5k showed the most potent biological activity against HEPG2 cancer cell line (IC50 = 0.81 μM for HEPG2 and IC50 = 0

  已设计，合成，结构确定了一系列含有1,4-苯并二恶烷（5a - 5q）的1,2,4-三唑衍生物，并将它们的生物活性作为潜在的MetAP2抑制剂进行了评估。所有合成的化合物都首先被报道。在化合物，化合物5K显示针对HEPG2癌细胞系的最有效的生物活性（IC 50  = 0.81μM为HEPG2和IC 50  = 0.93μM为的MetAP2），这是与阳性对照。通过将化合物5k置于MetAP2结构活性位点进行对接模拟，以探索可能的结合模型。凋亡和Western-blot检测结果表明该化合物5k对HEPG2癌细胞系具有良好的抗肿瘤活性。因此，在肿瘤生长抑制中具有有效抑制活性的化合物5k可能是针对HEPG2癌细胞的潜在抗肿瘤剂。