ethyl 2-oxo-7-(prop-2-yn-1-yloxy)-2H-chromene-3-carboxylate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: ethyl 2-oxo-7-(prop-2-yn-1-yloxy)-2H-chromene-3-carboxylate
• 英文别名: Ethyl 2-oxo-7-prop-2-ynoxychromene-3-carboxylate
• 化学式: C₁₅H₁₂O₅
• 分子量: 272.257
• InChiKey: ZSGAMBWKSZJYSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-oxo-7-(prop-2-yn-1-yloxy)-2H-chromene-3-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 2-oxo-7-(prop-2-yn-1-yloxy)-2H-chromene-3-carboxylic acid
  参考文献：
  名称：

  新型1,2,3-三唑-色酮羧酰胺衍生物的设计，合成和抗阿尔茨海默氏病活性。

  摘要：

  阿尔茨海默氏病（AD）是一种众所周知的神经退行性疾病，影响着全球数百万的老年人，相应的流行病学数据突显了该疾病的重要性。由于AD是一种多因素疾病，因此已通过临床试验的各种单靶标定向药物都失败了。因此，在靶向药物的发现和开发中已经考虑了与AD发作相关的各种因素。在这项工作中，设计，合成和评估了各种1,2,3-三唑-色酮羧酰胺，并对其胆碱酯酶抑制活性进行了评估。其中，N-（1-苄基哌啶-4-基）-7-（（1-（3,4-二甲基苄基）-1H-1,2,3-三唑-4-基）甲氧基）-2-氧代- 2H-chromene-3-carboxamide（11b）表现出最佳的乙酰胆碱酯酶抑制活性（IC50 = 1.80 µM）。它对丁酰胆碱酯酶无活性。应该注意的是，对化合物11b的BACE1抑制活性进行了评估，计算出的IC50 ＝21.13μM证实了所需的抑制活性。同样，该化合物在50 µM的PC12神经元中表现

  DOI：

  10.1016/j.bioorg.2018.10.065
• 作为产物：
  描述：

  diethyl 2-(2-(allyloxy)-4-(prop-2-ynyloxy)benzylidene)malonate 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 氘代二甲亚砜 、 二甲基亚砜 为溶剂， 反应 1.0h， 生成 ethyl 2-oxo-7-(prop-2-yn-1-yloxy)-2H-chromene-3-carboxylate
  参考文献：
  名称：

  Luminescent Lanthanide Complexes with Analyte-Triggered Antenna Formation

  摘要：

  A new strategy for accessing analyte-responsive luminescent probes is presented. The lanthanide luminescence of Eu and Tb centers is switched on by the analyte-triggered formation of a sensitizing antenna from a nonsensitizing caged precursor. As the cage can be freely varied, an array of probes for different analytes (pd(0/2+), H2O2, F-, beta-galactosidase) can be created from the same core structure. The probe design affords nanomolar to micromolar detection limits, provides the capability to detect two analytes in parallel, and can be utilized to monitor enzymatic activity in live cells.

  DOI：

  10.1021/ja3004045

文献信息

• 1,2,3-Triazole incorporated coumarin derivatives as potential antifungal and antioxidant agents
  作者：Mubarak H. Shaikh、Dnyaneshwar D. Subhedar、Firoz A. Kalam Khan、Jaiprakash N. Sangshetti、Bapurao B. Shingate

  DOI：10.1016/j.cclet.2015.11.003

  日期：2016.2

  A series of novel ethyl-7-((1-(benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxylates 8a-h as potential antifungal agents were synthesized via click chemistry. The antifungal activity was evaluated against five human pathogenic fungal strains, such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compound 8c, 8d, 8e and 8h

  一系列新型的7-（（（1-（苄基）-1H-1,2,3-三唑-4-基）甲氧基）乙基-2-氧代-2H-色烯-3-羧酸酯8a-h作为潜在的抗真菌剂试剂通过点击化学合成。评估了对五种人类病原性真菌菌株（如白色念珠菌，尖孢镰刀菌，黄曲霉，黑曲霉和新型隐球菌）的抗真菌活性。当与咪康唑相比时，发现化合物8c，8d，8e和8h与白色念珠菌等价，而与咪康唑相比，化合物8f的活性是对白色念珠菌的两倍，对白色念珠菌而言，化合物8f与氟康唑相当。还评估了基于香豆素的三唑衍生物的抗氧化剂活性，与标准药物相比，发现化合物8a是有效的抗氧化剂。此外，对新合成的化合物进行了分子对接研究，结果表明在真菌白色念珠菌酶P450细胞色素羊毛甾醇14α-脱甲基酶的活性位点具有良好的结合模式。此外，还分析了合成的化合物的ADME特性，并显示出有可能建立良好的口服药物候选物。
• Bioorthogonal Enzymatic Activation of Caged Compounds
  作者：Cornelia Ritter、Nathalie Nett、Carlos G. Acevedo‐Rocha、Richard Lonsdale、Katja Kräling、Felix Dempwolff、Sabrina Hoebenreich、Peter L. Graumann、Manfred T. Reetz、Eric Meggers

  DOI：10.1002/anie.201506739

  日期：2015.11.2

  as highly active and selective catalysts for the bioorthogonal uncaging of propargylic and benzylic ether protected substrates, including uncaging in living E. coli. observed selectivity is supported by induced‐fit docking and molecular dynamics simulations. This proof‐of‐principle study points towards the utility of bioorthogonal enzyme/protecting group pairs for applications in the life sciences

  据报道，工程细胞色素P450单加氧酶变体是用于炔丙基和苄基醚保护的底物的生物正交解包，包括在活的大肠杆菌中解包的高活性和选择性催化剂。感应拟合对接和分子动力学模拟支持观察到的选择性。这项原理验证研究指出了生物正交酶/保护基对在生命科学中的应用。
• Ethers of 7-hydroxy-coumarin useful as medicaments
  申请人：Unicler

  公开号：US04151291A1

  公开（公告）日：1979-04-24

  The invention provides novel esters of 7-hydroxycoumarin of the formula ##STR1## in which each of R.sub.1 and R.sub.2 represents a hydrogen atom, a C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, carboxy, carboxylate, C.sub.2 -C.sub.5 alkoxycarbonyl or nitrophenyl group, and R.sub.3 represents a hydrogen atom or a group of the formula --CH.sub.2 --Z in which Z represents a di(C.sub.1 -C.sub.4 alkyl)amino group, or a saturated heterocyclic amino radical containing 5 to 7 ring members which may contain a further heteroatom, and their pharmaceutically acceptable acid addition salts. The compounds are useful as medicaments, in particular as analgesics.

  该发明提供了新型7-羟基香豆素的酯类化合物，其化学式为##STR1##其中R.sub.1和R.sub.2分别代表氢原子，C.sub.1 -C.sub.4烷基，C.sub.2 -C.sub.4烯基，羧基，羧酸酯，C.sub.2 -C.sub.5烷氧羰基或硝基苯基；R.sub.3代表氢原子或具有--CH.sub.2 --Z的基团，其中Z代表二(C.sub.1 -C.sub.4烷基)氨基基团，或含有5到7个环成员的饱和杂环氨基基团，其中可能含有进一步的杂原子，以及它们的药用可接受的酸盐。这些化合物可用作药物，特别是作为镇痛药。
• Design, Synthesis and Cytotoxicity of Novel Dihydroartemisinin-Coumarin Hybrids via Click Chemistry
  作者：Ye Tian、Zhen Liang、Hang Xu、Yanhua Mou、Chun Guo

  DOI：10.3390/molecules21060758

  日期：——

  In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a–e, 11a–e, 12a–e, 13a–e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05–125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a–e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.

  为开发新型化疗药物，我们采用杂化策略设计了4类新型化合物。本研究通过点击化学合成了20种双氢青蒿素-香豆素杂化物（10a-e，11a-e，12a-e，13a-e），并通过高分辨质谱（HRMS）和核磁共振（NMR）对其结构进行了表征。我们在常氧或缺氧条件下，使用MTT法分别对3种癌细胞系（HCT-116、MDA-MB-231和HT-29）进行了细胞毒性活性测试。目标化合物表现出中等活性，IC50值在0.05至125.40微摩尔范围内，其中大部分化合物在缺氧条件下对HT-29细胞显示出更好的活性。大多数化合物在缺氧条件下的活性比常氧条件下高出1至10倍。化合物10a-e对HT-29细胞的选择性优于其他两种细胞系。这些结果表明，我们设计的CA IX抑制剂与其作用模式在一定程度上相符，值得进一步研究。
• Multiplex Detection of Enzymatic Activity with Responsive Lanthanide-Based Luminescent Probes
  作者：Elias Pershagen、K. Eszter Borbas

  DOI：10.1002/anie.201408560

  日期：2015.2.2

  Multiplex analyte detection in complex dynamic systems is desirable for the investigation of cellular communication networks as well as in medical diagnostics. A family of lanthanide‐based responsive luminescent probes for multiplex detection is reported. The high modularity of the probe design enabled the rapid assembly of both green and red emitters for a large variety of analytes by the simple exchange

  复杂动态系统中的多重分析物检测对于蜂窝通信网络的研究以及医学诊断而言是理想的。据报道，基于镧系元素的响应型发光探针可进行多重检测。探针设计的高度模块化通过分别简单地交换镧系元素或可裂解分析物的笼状基团，可以快速组装绿色和红色发射体，以用于多种分析物。演示了多达三种分析物的实时三色检测，从而为相互联系的生物过程的非侵入性研究奠定了基础。