1-(4-Bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one | 64376-21-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 1-(4-Bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one
• CAS: 64376-21-2
• 化学式: C₁₇H₁₃BrO₃
• 分子量: 345.192
• InChiKey: BMXAHUJDURXUOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-Bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one 在 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 20.0h， 生成 2-[5-(4-Bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-3,4-dihydropyrazol-2-yl]-4-(4-methoxyphenyl)-1,3-thiazole
  参考文献：
  名称：

  以苯并二恶唑为潜在抗癌剂的噻唑基-吡唑啉衍生物的合成，分子对接和评价

  摘要：

  已经设计并合成了一系列含有苯并二恶唑（C1-C20）的新型噻唑基-吡唑啉衍生物。在合成的化合物中，2-（5-（苯并[ d ] [1,3]二恶酚-5-基）-3-（4-溴苯基）-4,5-二氢-1 H-吡唑-1-基）-4-（4-溴苯基）噻唑（C6）对HER-2表现出最强的抑制活性（HER-2的IC 50  = 0.18μM）。抗增殖试验结果表明，化合物C6在体外对MCF-7和B16-F10具有很高的抗增殖活性，IC 50值分别为0.09和0.12μM，与阳性对照厄洛替尼相当。进一步进行对接仿真以确定可能的结合模型。根据初步结果，在肿瘤生长中具有强抑制活性的化合物C6将是潜在的抗癌药。

  DOI：

  10.1016/j.bmc.2012.11.020
• 作为产物：
  描述：

  3,4-二羟基苯甲醛 在 potassium carbonate 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1-(4-Bromophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)prop-2-en-1-one
  参考文献：
  名称：

  含有苯并氧杂环和磺酰胺部分的二氢吡唑衍生物选择性和有效地抑制 COX-2：设计、合成和抗结肠癌活性评估

  摘要：

  已发现环氧合酶-2 (COX-2) 作为花生四烯酸的限速代谢酶与肿瘤发生、血管生成、转移以及细胞凋亡抑制有关，被认为是癌症治疗的有吸引力的治疗靶点。在我们的研究中，通过对已知 COX-2 抑制剂的计算机辅助药物分析，将一系列含有苯并氧杂环和磺酰胺部分的二氢吡唑衍生物设计为高效且选择性的 COX-2 抑制剂。共合成了26种化合物，多角度评价了体外和体内COX-2抑制作用和药理效率。其中，化合物4b对SW620细胞表现出最优异的抗增殖活性，IC50比塞来昔布（IC50 = 1.29±0.04 µM）为0.86±0.02 µM。

  DOI：

  10.3390/molecules24091685

文献信息

• 4,5-Dihydropyrazole derivatives containing oxygen-bearing heterocycles as potential telomerase inhibitors with anticancer activity
  作者：Yin Luo、Yang Zhou、Jie Fu、Hai-Liang Zhu

  DOI：10.1039/c4ra02200a

  日期：——

  Telomere and telomerase were closely related to the occurrence and development of some cancers. After the key active site of telomerase was identified, to enhance the ability of dihydropyrazole derivatives to inhibit telomerase, we designed a series of novel 4,5-dihydropyrazole derivatives containing heterocyclic oxygen moiety based on previous studies. The telomerase inhibition assay showed that compound 10a displayed the most potent inhibitory activity with an IC50 value of 0.6 μM for telomerase. The antiproliferative assay showed that 10a exhibited high activity against human gastric cancer cell SGC-7901 with an IC50 value of 10.95 ± 0.60 μM. Flow cytometric analysis and western blot results showed that 10a induced both apoptosis and autophagy. A docking simulation showed that 10a could bind well to the active site of telomerase and act as a telomerase inhibitor. The 3D-QSAR model was also built to provide a more pharmacological understanding that could be used to design new agents with more potent telomerase inhibitory activity.

  端粒和端粒酶与某些癌症的发生发展密切相关。在鉴定出端粒酶关键活性部位后，基于以往的研究，为了增强二氢吡唑衍生物抑制端粒酶的能力，我们设计了一系列含有杂环氧基的新型4,5-二氢吡唑衍生物。端粒酶抑制实验表明，化合物10a显示出最强的抑制活性，其对端粒酶的IC50值为0.6 μM。细胞增殖实验表明，10a对胃癌细胞SGC-7901具有很高的活性，其IC50值为10.95 ± 0.60 μM。流式细胞分析和western blot结果显示，10a可诱导细胞凋亡和自噬。对接模拟显示，10a可与端粒酶的活性位点很好地结合，并作为端粒酶抑制剂发挥作用。同时，为了能更好地指导设计出新的具有更强端粒酶抑制活性的化合物，我们构建了三维定量构效关系(3D-QSAR)模型。
• Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors
  作者：Yin Luo、Shuai Zhang、Ke-Ming Qiu、Zhi-Jun Liu、Yu-Shun Yang、Jie Fu、Wei-Qing Zhong、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2012.12.010

  日期：2013.2

  A series of novel aryl-2H-pyrazole derivatives bearing 1,4-benzodioxan or 1,3-benzodioxole moiety were designed as potential telomerase inhibitors to enhance the ability of aryl-2H-pyrazole derivatives to inhibit telomerase, a target of anticancer. The telomerase inhibition tests showed that compound 16A displayed the most potent inhibitory activity with IC50 value of 0.9 mu M for telomerase. The antiproliferative tests showed that compound 16A exhibited high activity against human gastric cancer cell SGC-7901 and human melanoma cell B16-F10 with IC50 values of 18.07 and 5.34 mu M, respectively. Docking simulation showed that compound 16A could bind well with the telomerase active site and act as telomerase inhibitor. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent telomerase inhibitory activity. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis and antihepatotoxic activity of 5-(2,3-dihydro-1,4-benzodioxane-6-yl)-3-substituted-phenyl-4,5-dihydro-1H-pyrazole derivatives
  作者：Habibullah Khalilullah、Shamshir Khan、Mohamed Jawed Ahsan、Bahar Ahmed

  DOI：10.1016/j.bmcl.2011.10.056

  日期：2011.12

  In continuance of our search for newer antihepatotoxic agents some novel pyrazoline derivatives containing 1,4-dioxane ring system were synthesized starting from 3-(2,3-dihydro-1,4-benzodioxane-6-yl)-1-substituted-phenylprop-2-en-1-one. Some of the synthesized compounds were evaluated for antihepatotoxic activity against CCl4-induced hepatotoxicity in rats. Among them some compounds have shown significant antihepatotoxic activity comparable to standard drug silymarin. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives containing benzodioxole as potential anticancer agents
  作者：Hai-Hong Wang、Ke-Ming Qiu、Hong-En Cui、Yu-Shun Yang、Yin-Luo、Man Xing、Xiao-Yang Qiu、Li-Fei Bai、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.11.020

  日期：2013.1

  A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1–C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibitory activity for HER-2 (IC50 = 0.18 μM for HER-2). Antiproliferative assay results indicated that compound

  已经设计并合成了一系列含有苯并二恶唑（C1-C20）的新型噻唑基-吡唑啉衍生物。在合成的化合物中，2-（5-（苯并[ d ] [1,3]二恶酚-5-基）-3-（4-溴苯基）-4,5-二氢-1 H-吡唑-1-基）-4-（4-溴苯基）噻唑（C6）对HER-2表现出最强的抑制活性（HER-2的IC 50  = 0.18μM）。抗增殖试验结果表明，化合物C6在体外对MCF-7和B16-F10具有很高的抗增殖活性，IC 50值分别为0.09和0.12μM，与阳性对照厄洛替尼相当。进一步进行对接仿真以确定可能的结合模型。根据初步结果，在肿瘤生长中具有强抑制活性的化合物C6将是潜在的抗癌药。
• Dihydropyrazole Derivatives Containing Benzo Oxygen Heterocycle and Sulfonamide Moieties Selectively and Potently Inhibit COX-2: Design, Synthesis, and Anti-Colon Cancer Activity Evaluation
  作者：Xiao-Qiang Yan、Zhong-Chang Wang、Bo Zhang、Peng-Fei Qi、Gui-Gen Li、Hai-Liang Zhu

  DOI：10.3390/molecules24091685

  日期：——

  Cyclooxygenase-2 (COX-2) as a rate-limiting metabolism enzyme of arachidonic acid has been found to be implicated in tumor occurrence, angiogenesis, metastasis as well as apoptosis inhibition, regarded as an attractive therapeutic target for cancer therapy. In our research, a series of dihydropyrazole derivatives containing benzo oxygen heterocycle and sulfonamide moieties were designed as highly potent

  已发现环氧合酶-2 (COX-2) 作为花生四烯酸的限速代谢酶与肿瘤发生、血管生成、转移以及细胞凋亡抑制有关，被认为是癌症治疗的有吸引力的治疗靶点。在我们的研究中，通过对已知 COX-2 抑制剂的计算机辅助药物分析，将一系列含有苯并氧杂环和磺酰胺部分的二氢吡唑衍生物设计为高效且选择性的 COX-2 抑制剂。共合成了26种化合物，多角度评价了体外和体内COX-2抑制作用和药理效率。其中，化合物4b对SW620细胞表现出最优异的抗增殖活性，IC50比塞来昔布（IC50 = 1.29±0.04 µM）为0.86±0.02 µM。