ethyl 3-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)propanoate | 251361-29-2

• 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 3-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)propanoate
• 英文别名: ethyl 7-hydroxy-4,8-dimethylcoumarin-3-propanoate；ethyl 3-(7-hydroxy-4,8-dimethyl-2-oxochromen-3-yl)propanoate
• CAS: 251361-29-2
• 化学式: C₁₆H₁₈O₅
• mdl: MFCD03848125
• 分子量: 290.316
• InChiKey: OQZCNKKWUHVSSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2932209090

反应信息

• 作为反应物：
  描述：

  ethyl 3-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)propanoate 在 草酰氯 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 46.0h， 生成 3-[7-[[4-(4-chlorophenyl)phenyl]methoxy]-4,8-dimethyl-2-oxochromen-3-yl]-N-methylpropanamide
  参考文献：
  名称：

  Coumarin-Based Inhibitors of Bacillus anthracis and Staphylococcus aureus Replicative DNA Helicase: Chemical Optimization, Biological Evaluation, and Antibacterial Activities

  摘要：

  The increasing prevalence of drug-resistant bacterial infections demands the development of new antibacterials that are not subject to existing mechanisms of resistance. Previously, we described coumarin-based inhibitors of an underexploited bacterial target, namely the replicative helicase. Here we report the synthesis and evaluation of optimized coumarin-based inhibitors with 9-18-fold increased potency against Staphylococcus aureus (Sa) and Bacillus anthracis (Ba) helicases. Compounds 20 and 22 provided the best potency, with IC50 values of 3 and 1 mu M, respectively, against the DNA duplex strand-unwinding activities of both B. anthracis and S. aureus helicases without affecting the single strand DNA-stimulated ATPase activity. Selectivity index (SI = CC50/MIC) values against S. aureus and B. anthracis for compound 20 were 33 and 66 and for compound 22 were 20 and 40, respectively. In addition, compounds 20 and 22 demonstrated potent antibacterial activity against multiple ciprofloxacin-resistant MRSA strains, with MIC values ranging between 0.5 and 4.2 mu g/mL.

  DOI：

  10.1021/jm300922h
• 作为产物：
  描述：

  乙酰戊二酸二乙酯 、 2,6-二羟基甲苯 在 盐酸 作用下， 以 乙醇 为溶剂， 以62%的产率得到ethyl 3-(7-hydroxy-4,8-dimethyl-2-oxo-2H-chromen-3-yl)propanoate
  参考文献：
  名称：

  修饰的补骨脂素类似物的合成

  摘要：

  通过将呋喃部分线性环化到香豆素体系中，合成类似于补骨脂素的3-（5-甲基-7-氧杂呋喃[3,2-g] chromen-6-基）丙酸。该论文的英文版：Russian Journal of Bioorganic Chemistry，2004年，第1卷。30号 3; 另请参见http://www.maik.ru。

  DOI：

  10.1023/b:rubi.0000030137.88504.10

文献信息

• Synthesis and biological evaluation of coumarincarboxylic acids as inhibitors of gyrase B. L-rhamnose as an effective substitute for L-noviose
  作者：Didier Ferroud、Jeannine Collard、Michel Klich、Claudine Dupuis-Hamelin、Pascale Mauvais、Patrice Lassaigne、Alain Bonnefoy、Branislav Musicki

  DOI：10.1016/s0960-894x(99)00493-x

  日期：1999.10

  A series of novobiocin-like coumarincarboxylic acids has been prepared bearing the L-rhamnosyl moiety as the sugar portion of the molecule. The similar DNA gyrase inhibitory activity of the novel class of coumarins to that of novobiocin demonstrates that L-rhamnose can effectively replace L-noviose. Introduction of alkyl side-chains at C-5 of coumarin leads to improved in vitro antibacterial properties

  已经制备了一系列带有L-鼠李糖基部分作为分子糖部分的新生物素样香豆素羧酸。新型香豆素对DNA促旋酶的抑制活性与新霉素相似，这表明L-鼠李糖可以有效替代L-鼠新糖。在香豆素的C-5处引入烷基侧链可改善新系列的体外抗菌性能。
• Nonpeptidic Selective Inhibitors of the Chymotrypsin-Like (β5 i) Subunit of the Immunoproteasome
  作者：Izidor Sosič、Martina Gobec、Boris Brus、Damijan Knez、Matej Živec、Janez Konc、Samo Lešnik、Mitja Ogrizek、Aleš Obreza、Dušan Žigon、Dušanka Janežič、Irena Mlinarič-Raščan、Stanislav Gobec

  DOI：10.1002/anie.201600190

  日期：2016.5.4

  of the immunoproteasome has been associated with autoimmune diseases, inflammatory diseases, and various types of cancer. Selective inhibitors of the immunoproteasome are not only scarce, but also almost entirely restricted to peptide‐based compounds. Herein, we describe nonpeptidic reversible inhibitors that selectively block the chymotrypsin‐like (β5i) subunit of the human immunoproteasome in the

  免疫蛋白酶体的高表达与自身免疫性疾病，炎性疾病和各种类型的癌症有关。免疫蛋白酶体的选择性抑制剂不仅稀缺，而且几乎完全限于基于肽的化合物。本文中，我们描述了非肽类可逆抑制剂，可在低微摩尔范围内选择性阻断人免疫蛋白酶体的胰凝乳蛋白酶样（β5i）亚基。然后将最有效的可逆作用化合物转化为共价，不可逆的非肽类抑制剂，这些抑制剂保留了对β5i亚基的选择性。此外，在基于细胞的测定中，这些抑制剂可区分免疫蛋白酶体和组成型蛋白酶体。除了缺乏细胞毒性外，
• [EN] PSORALEN DERIVATIVES AS NON-PEPTIDIC INHIBITORS OF CHYMOTRYPSIN-LIKE ACTIVITY OF THE IMMUNOPROTEASOME<br/>[FR] DÉRIVÉS DU PSORALÈNE UTILISÉS COMME INHIBITEURS NON PEPTIDIQUES DE L'ACTIVITÉ DE TYPE CHYMOTRYPSINE DE L'IMMUNOPROTÉASOME
  申请人：UNIV LJUBLJANI

  公开号：WO2016151483A1

  公开（公告）日：2016-09-29

  This invention relates to new inhibitors of chymothrypsin-like activity of the immunoproteasome (inhibitors of β5ί or LMP7 subunit) with the general formula (I), where substituents are described in patent description. Compounds can be in the form of pure enantiomers or as racemic mixtures, or in the form of pharmaceutically acceptable salts. The present invention relates to the use of these inhibitors for the treatment of diseases where immunoproteasome activity is increased.

  这项发明涉及免疫蛋白酶体（β5ί或LMP7亚基的抑制剂）的新抑制剂，其通用化学式为（I），其中取代基在专利说明中描述。化合物可以是纯对映体形式，也可以是混合物形式，或者是药用可接受的盐形式。本发明涉及利用这些抑制剂治疗免疫蛋白酶体活性增加的疾病。
• Psoralen derivatives as inhibitors of NF- $$\upkappa \hbox {B/DNA}$$ κ B/DNA interaction: the critical role of the furan ring
  作者：Giovanni Marzaro、Ilaria Lampronti、Monica Borgatti、Paolo Manzini、Roberto Gambari、Adriana Chilin

  DOI：10.1007/s11030-015-9586-2

  日期：2015.8

  Simplified analogues of previously reported NF- $$\upkappa \hbox B/DNA}$$ interaction inhibitors, lacking the furan moiety, were synthesized and evaluated by performing experiments based on electrophoretic mobility shift assay (EMSA). The synthetic modifications led to simpler coumarin derivatives with lower activity allowing to better understand the minimal structural requirement for the binding to NF- $$\upkappa \hbox B}$$ .

  通过基于电泳迁移率测定（EMSA）的实验，合成并评估了以前报道的 NF- $$\upkappa （hbox B/DNA}$$ 相互作用抑制剂的简化类似物，这些类似物缺少呋喃分子。通过合成修饰得到了活性较低的简单香豆素衍生物，从而更好地理解了与 NF- $$\upkappa \hbox B}$ 结合的最低结构要求。
• Spectroscopic, photophysical and photochemical properties of newly metallo-phthalocyanines containing coumarin derivative
  作者：Aylin Çapkın、Mehmet Pişkin、Mahmut Durmuş、Mustafa Bulut

  DOI：10.1016/j.molstruc.2020.128145

  日期：2020.8

  phthalocyanine skeleton and metal’ nature in the phthalocyanine cavity on photophysical and photochemical properties were investigated by comparing with previous analogues (magnesium, zinc, and indium phthalocyanines containing coumarin derivative with different functional groups). The spectroscopic, photophysical, photochemical data and results obtained for each of these phthalocyanines show that they may have

  摘要 新型、易溶且非聚集的外周或非外周四乙基 7-氧-4,8-​​二甲基香豆素-3-丙酸取代镁 (II)、锌 (II) 和铟 (III) 乙酸酞菁是合成的。它们通过广为人知的光谱方法进行表征，例如 UV-vis、IR、MALDI-TOF 质谱、1H NMR 光谱和元素分析。在 N, N-二甲基甲酰胺中研究了光物理和光化学特性，以确定这些酞菁中的每一种作为光敏剂的可用性。通过与以前的类似物（镁、锌、和含有不同官能团的香豆素衍生物的铟酞菁）。每种酞菁的光谱、光物理、光化学数据和结果表明，它们有可能在光动力疗法中用作光敏剂。