7-(4-bromobutoxy)-4-phenyl-2H-chromen-2-one | 1351984-77-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: 7-(4-bromobutoxy)-4-phenyl-2H-chromen-2-one
• CAS: 1351984-77-4
• 化学式: C₁₉H₁₇BrO₃
• 分子量: 373.246
• InChiKey: ODZUOXBHZOOKIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.01
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  39.44
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  7-(4-bromobutoxy)-4-phenyl-2H-chromen-2-one 在 sodium azide 、 palladium on activated charcoal 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成
  参考文献：
  名称：

  衍生自芳基磺酰胺和香豆素的构象限制性糖缀合物：肿瘤相关碳酸酐酶抑制剂的新家族

  摘要：

  碳酸酐酶 (CA) 在无数生物事件中的参与使得开发这些金属酶的新抑制剂成为当前药物化学的热门话题。特别地，CA IX 和 XII 是膜结合酶，负责肿瘤存活和化学抗性。在此，基于双环碳水化合物的亲水性尾巴（咪唑烷-2-硫酮）已附加到 CA 靶向药效团（芳基磺酰胺、香豆素）上，目的是研究尾巴的构象限制对 CA 抑制的影响。为此，将基于磺胺基或香豆素的异硫氰酸酯与还原性 2-氨基糖偶联，然后依次进行酸促进的相应硫脲的分子内环化和脱水反应，以良好的总收率提供了相应的双环咪唑啉-2-硫酮。在人 CAs 的体外抑制中，分析了碳水化合物构型、磺胺基序在芳基片段上的位置以及香豆素上的连接长度和取代模式的影响。关于磺胺类抑制剂，最好的模板是 d-半乳糖构型的碳水化合物残基，芳基部分 (9b) 的间位取代，对 CA XII 的 Ki 在低 nM 范围 (5.1 nM) 内，并且显着选择性指数（CA I 为 1531，CA

  DOI：

  10.3390/ijms24119401
• 作为产物：
  描述：

  苯甲酰乙酸乙酯 在 硫酸 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 7-(4-bromobutoxy)-4-phenyl-2H-chromen-2-one
  参考文献：
  名称：

  新型香豆素-类固醇/萜类杂交体：体外和计算机抗癌研究

  摘要：

  我们合成了一系列新型香豆素-类固醇和三萜杂交体，并通过分子对接计算和体外抗增殖测定评估了它们的潜在抗癌活性。这些衍生自雌酮和齐墩果酸的杂交体通过不同长度的烃垫片连接。针对人芳香化酶的分子对接研究揭示了强烈的相互作用，特别是对于化合物 11d，它表现出显着的结合亲和力 （-12.6308 kcal/mol）。体外实验表明，化合物 6b 和 11d 具有显着的抗增殖作用，对 WiDr （结肠） 和 HeLa （子宫颈） 癌细胞的 GI50 值分别为 5.4 和 7.0 μM。这些发现突出了这些杂交体作为靶向芳香酶的新型抗癌剂的潜力，值得进一步研究和优化。

  DOI：

  10.1002/cbdv.202401315

文献信息

• Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer’s disease: Design, synthesis and biological evaluation
  作者：Qi He、Jing Liu、Jin-Shuai Lan、Jiaoli Ding、Yongbing Sun、Yuanying Fang、Neng Jiang、Zunhua Yang、Liyuan Sun、Yi Jin、Sai-Sai Xie

  DOI：10.1016/j.bioorg.2018.09.010

  日期：2018.12

  A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068 mu M and 0.0089 mu M for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114 mu M for hAChE; 0.101 mu M for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500 mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
• BENZOPYRONE DERIVATIVE AND USE THEREOF
  申请人：Huazhong University of Science and Technology

  公开号：EP2698369B1

  公开（公告）日：2017-02-01
• Synthesis and Biological Investigation of Coumarin Piperazine (Piperidine) Derivatives as Potential Multireceptor Atypical Antipsychotics
  作者：Yin Chen、Songlin Wang、Xiangqing Xu、Xin Liu、Minquan Yu、Song Zhao、Shicheng Liu、Yinli Qiu、Tan Zhang、Bi-Feng Liu、Guisen Zhang

  DOI：10.1021/jm400408r

  日期：2013.6.13

  The discovery and synthesis of potential and novel antipsychotic coumarin derivatives, associated with potent dopamine 132, D3, and serotonin S-HT1A and S-HT2A, receptor properties, are the focus of the present article. The most-promising derivative was 7-(4-(4-(6-fluorobenzo[d]-isoxazol-3-yl)-piperidin-1-yl)butoxy)-4-methyl-8-chloro-2H- chromen-2-one (17m). This derivative possesses unique pharmacological features, including high affinity for dopamine D-2 and D-3 and serotonin S-HT1A and 5-HT2A receptors. Moreover, it possesses low affinity for S-HT2C and H-1 receptors (to reduce the risk of obesity associated with chronic treatment) and hERG channels (to reduce the incidence of torsade des pointes). In animal models, compound 17m inhibited apomorphine-induced climbing behavior, MK-801-induced hyperactivity, and the conditioned avoidance response without observable catalepsy at the highest dose tested. Further, fewer preclinical adverse events were noted with 17m compared with risperidone in assays that measured prolactin secretion and weight gain. Acceptable pharmacokinetic properties were also noted with 17m. Taken together, 17m may constitute a novel class of drugs for the treatment of schizophrenia.
• Design, synthesis and evaluation of novel tacrine–coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease
  作者：Sai-Sai Xie、Xiao-Bing Wang、Jiang-Yan Li、Lei Yang、Ling-Yi Kong

  DOI：10.1016/j.ejmech.2013.03.051

  日期：2013.6

  A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced,beta-amyloid (A beta) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 mu M) and A beta aggregation (67.8%, 20 mu M). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 mu M) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment. (C) 2013 Elsevier Masson SAS. All rights reserved.