1-(3-chloro-4-hydroxyphenyl)butane-1-one | 500127-73-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-chloro-4-hydroxyphenyl)butane-1-one
• 英文别名: 1-(3-chloro-4-hydroxyphenyl)-1-butanone；1-(3-chloro-4-hydroxy-phenyl)-butan-1-one；1-(3-Chlor-4-hydroxy-phenyl)-butan-1-on；1-(3-chloro-4-hydroxyphenyl)butan-1-one
• CAS: 500127-73-1
• 化学式: C₁₀H₁₁ClO₂
• 分子量: 198.649
• InChiKey: WCEAOVHOUWMGEC-UHFFFAOYSA-N

物化性质

• 熔点：
  122 °C
• 沸点：
  335.5±27.0 °C(Predicted)
• 密度：
  1.208±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-4-hydroxyphenyl)butane-1-one 在 四甲基乙二胺 、 potassium tert-butylate 、 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 85.0h， 生成 ethyl (2-chloro-4-(2-methylenebutyryl)phenoxy)acetate
  参考文献：
  名称：

  A New Lead for Nonpeptidic Active-Site-Directed Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus Main Protease Discovered by a Combination of Screening and Docking Methods

  摘要：

  The coronavirus main protease, M-pro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M-pro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M-pro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K-i value of 35.3 mu M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

  DOI：

  10.1021/jm0501782
• 作为产物：
  描述：

  1-[3-chloro-4-(2-propynyloxy)phenyl]-1-butanone 在 bis-triphenylphosphine-palladium(II) chloride 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以65%的产率得到1-(3-chloro-4-hydroxyphenyl)butane-1-one
  参考文献：
  名称：

  在无铜条件下，钯催化的水性介质中O / N-炔丙基保护基的裂解。

  摘要：

  [反应：见正文]已研究了无铜钯介导的水介质中O / N-炔丙基键的裂解，为酚和苯胺的脱保护提供了一种温和而方便的方法。该方法可用于从芳基醚和胺中选择性除去炔丙基，而不会影响底物中存在的各种未保护的官能团。讨论了反应的机理和范围。

  DOI：

  10.1021/ol027382t

文献信息

• Synthesis and Evaluation of Non-peptidic Cysteine Protease Inhibitors of P. falciparum Derived from Etacrynic Acid
  作者：Marie-Adrienne Dude、Ulrich Kaeppler、Monika Herb、Markus Schiller、Franziska Schulz、Birgit Vedder、Saskia Heppner、Gabriele Pradel、Jiri Gut、Philip Rosenthal、Tanja Schirmeister、Matthias Leippe、Christoph Gelhaus

  DOI：10.3390/molecules14010019

  日期：——

  A series of etacrynic acid derivatives was synthesized and screened for their in vitro activity against Plasmodium falciparum, as well as their activity against recombinantly expressed falcipain-2 and -3. The two most active compounds of the series displayed IC50 values of 9.0 and 18.8 μM against Plasmodia.

  一系列依他尼酸衍生物被合成并筛选其对恶性疟原虫的体外活性，以及它们对重组表达的法西平-2和法西平-3的活性。该系列中活性最强的两种化合物对疟原虫的IC50值分别为9.0和18.8 μM。
• PROCESS FOR SYNTHESIS OF 2-SUBSTITUTED PYRROLIDINES AND PIPERADINES
  申请人：Leleti Rajender Reddy

  公开号：US20120302756A1

  公开（公告）日：2012-11-29

  The present invention provides a highly efficient, versatile one-step process for asymmetric synthesis of either diastereomer of 2-substituted pyrrolidines from a single starting material with excellent yields and high diastereoselectivety. Also provided is a method for the asymmetric synthesis of both diastereomers of 2-substituted piperidines with good yields and excellent diastereoselectivety. Diasteroselectivity is controlled effectively by choice of reducing agent.

  本发明提供了一种高效、多功能的单步不对称合成方法，用于从单一起始物质合成2-取代吡咯烷的任一对映异构体，产率高，对映选择性高。同时还提供了一种方法，用于不对称合成2-取代哌啶的两个对映异构体，产率好，对映选择性优异。还通过选择还原剂有效地控制对映选择性。
• Nguyen-Hoan; Buu-Hoi, Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1947, vol. 224, p. 1363
  作者：Nguyen-Hoan、Buu-Hoi

  DOI：——

  日期：——
• [EN] PROCESS FOR SYNTHESIS OF 2-SUBSTITUTED PYRROLIDINES AND PIPERADINES<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE PYRROLIDINES ET DE PIPÉRIDINES SUBSTITUÉES EN POSITION 2
  申请人：NOVARTIS AG

  公开号：WO2011103263A2

  公开（公告）日：2011-08-25

  The present invention provides a highly efficient, versatile one-step process for asymmetric synthesis of either diastereomer of 2-substituted pyrrolidines from a single starting material with excellent yields and high diastereoselectivety. Also provided is a method for the asymmetric synthesis of both diastereomers of 2-substituted piperidines with good yields and excellent diastereoselectivety. Diasteroselectivity is controlled effectively by choice of reducing agent.
• A New Lead for Nonpeptidic Active-Site-Directed Inhibitors of the Severe Acute Respiratory Syndrome Coronavirus Main Protease Discovered by a Combination of Screening and Docking Methods
  作者：Ulrich Kaeppler、Nikolaus Stiefl、Markus Schiller、Radim Vicik、Alexander Breuning、Werner Schmitz、Daniel Rupprecht、Carsten Schmuck、Knut Baumann、John Ziebuhr、Tanja Schirmeister

  DOI：10.1021/jm0501782

  日期：2005.11.1

  The coronavirus main protease, M-pro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M-pro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed M-pro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a K-i value of 35.3 mu M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.