1-(6-methoxy-2-naphthyl)-4,4,4-trifluorobutane-1,3-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(6-methoxy-2-naphthyl)-4,4,4-trifluorobutane-1,3-dione
• 英文别名: 4,4,4-Trifluoro-1-(6-methoxynaphthalen-2-yl) butane-1,3-dione；4,4,4-trifluoro-1-(6-methoxynaphthalen-2-yl)butane-1,3-dione
• 化学式: C₁₅H₁₁F₃O₃
• 分子量: 296.246
• InChiKey: TUNLICZOEVMDCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(6-methoxy-2-naphthyl)-4,4,4-trifluorobutane-1,3-dione 在 盐酸 、 platinum(IV) oxide 、 氢气 作用下， 以 乙醇 为溶剂， 生成 4-[5-(6-methoxy-naphthalen-2-yl)-3-trifluoromethyl-pyrazol-1-yl]-phenylamine
  参考文献：
  名称：

  Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus

  摘要：

  Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.018
• 作为产物：
  描述：

  三氟乙酸乙酯 、 6-甲氧基-2-乙酰萘 在 C₂H₅O^(1-)*HNa 作用下， 以 乙醇 为溶剂， 以87%的产率得到1-(6-methoxy-2-naphthyl)-4,4,4-trifluorobutane-1,3-dione
  参考文献：
  名称：

  六种含乙酰丙酮化物衍生物的钒基配合物的合成，表征和细胞活力测试

  摘要：

  已知钒化合物显示出许多治疗作用，即模拟胰岛素和心血管作用。许多钒基配合物的抗增殖和凋亡活性的证据，以及低毒性，使这些金属化合物成为有希望的抗肿瘤治疗剂。在目前的工作中，我们描述了六个新的钒氧杂环丁烷配合物的合成和完整表征，这些配合物具有在β-二羰基部分上不对称取代的乙酰丙酮酸酯衍生物：该配合物在固态和溶液中均具有特征。我们的结果表明，所有复合物均处于方形金字塔形几何结构中。顺式在强配位溶剂的存在下，赤道平面中的异构体是有利的。EPR证据表明，所有复合物均为双螯合物形式，尽管在两种情况下似乎也存在单螯合物。在非肿瘤和肿瘤细胞系上进行的初步测试表明，这些复合物可有效抑制细胞活力，并引起肿瘤和非肿瘤细胞的独特应答。

  DOI：

  10.1016/j.jinorgbio.2013.07.015

文献信息

• Direct Conversion of Aromatic Ketones to Arenecarboxylic Esters via Carbon–Carbon Bond-Cleavage Reactions
  作者：Guodong Yin、Meng Gao、Zihua Wang、Yandong Wu、Anxin Wu

  DOI：10.1246/bcsj.81.369

  日期：2008.3.15

  Aromatic methyl ketones, β-keto esters, and trifluoromethyl-1,3-diketones can be directly converted to arenecarboxylic esters via carbon–carbon bond cleavage of pyridinium iodide intermediates in t...

  芳香族甲基酮、β-酮酯和三氟甲基-1,3-二酮可以通过碘化吡啶中间体的碳-碳键断裂直接转化为芳烃羧酸酯...
• Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore
  作者：Sunil K. Singh、V. Saibaba、K. Srinivasa Rao、P. Ganapati Reddy、Pankaj R. Daga、S. Abdul Rajjak、Parimal Misra、Y. Koteswar Rao

  DOI：10.1016/j.ejmech.2005.03.016

  日期：2005.10

  Diverse analogs of 1,5-diarylpyrazoles having 3-hydroxymethyl-4-sulfamoyl (SO2NH2)/methyl sulfonyl (SO2Me)-pheny group at N-1 were synthesized and evaluated for their in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The SAR study mainly involved the variations at positions C-3, C-5 and N-1 of the pyrazole ring. Several small hydrophobic groups at/around position-4 of C-5 phenyl, viz. 3,4-dimethylphenyl analog 9, 3-methyl-4-methylsulfanylphenyl analog 14 and 2,3-dihydrobenzo[b]thiophenyl analog 17, exhibited impressive COX-2 inhibitory potency. In general, the sulfonamide analogues with a CHF2 at C-3 were found to be more potent than those having a CF3 group. The three dimensional quantitative structure activity relationship comprising comparative molecular field analysis (3D-QSAR-CoMFA) afforded the models with high predictivity which further validated the acceptance of hydroxymethyl (CH2OH) group in the hydrophilic pocket of the COX-2 enzyme. (c) 2005 Elsevier SAS. All rights reserved.
• Synthesis and anti-microbial activity of some new fluorinated 1H-pyrazoles
  作者：Dun-Jia Wang、Ling Fan、Chun-Yang Zheng、Zheng-Dong Fang

  DOI：10.1016/j.jfluchem.2010.01.005

  日期：2010.5

  Several new trifluoromethyl-1H-pyrazoles were prepared by reaction of hydrazine monohydrate with 1,3-diketones. Their structures were confirmed by elemental analysis, IR, H-1 NMR and EI-MS spectroscopy. The anti-microbial activities of the newly synthesized compounds were examined by disc diffusion method against Escherichia coli, Staphylococcus aureus, Pyricularia oryzae and Rhizoctnia solani. All the trifluoromethyl-1H-pyrazoles exhibited a certain degree of anti-bacterial and anti-fungal activities. (C) 2010 Elsevier B.V. All rights reserved.
• Reactions of 1,3-Diketones with a Dipeptide Isothiazolidin-3-one: Toward Agents That Covalently Capture Oxidized Protein Tyrosine Phosphatase 1B
  作者：Kasi Viswanatharaju Ruddraraju、Zachary D. Parsons、Elizabeth M. Llufrio、Natasha L. Frost、Kent S. Gates

  DOI：10.1021/acs.joc.5b01949

  日期：2015.12.18

  Protein tyrosine phosphatase 1B (PTP1B) is a validated therapeutic target for the treatment of type 2 diabetes; however, the enzyme has been classified by some as an "undruggable target". Here we describe studies directed toward the development of agents that covalently capture the sulfenyl amide "oxoform" of PTP1B generated during insulin signaling events. The sulfenyl amide residue found in oxidized PTP1B presents a unique electrophilic sulfur center that may be exploited in drug and probe design. Covalent capture of oxidized PTP1B could permanently disable the intracellular pool of enzyme involved in regulation of insulin signaling. Here, we employed a dipeptide model of oxidized PTP1B to investigate the nucleophilic capture of the sulfenyl amide residue by structurally diverse 1,3-diketones. All of the 1,3-diketones examined here reacted readily with the electrophilic sulfur center in the sulfenyl amide residue to generate stable covalent attachments. Several different types of products were observed, depending upon the substituents present on the 1,3-diketone. The results provide a chemical foundation for the development of agents that covalently capture the oxidized form of PTP1B generated in cells during insulin signaling events.
• Development of novel antibacterial agents against methicillin-resistant Staphylococcus aureus
  作者：Hao-Chieh Chiu、Su-Lin Lee、Naval Kapuriya、Dasheng Wang、Yi-Ru Chen、Sung-Liang Yu、Samuel K. Kulp、Lee-Jene Teng、Ching-Shih Chen

  DOI：10.1016/j.bmc.2012.06.018

  日期：2012.8

  Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health because of its resistance to multiple antibiotics most commonly used to treat infection. In this study, we report the unique ability of the cyclooxygenase-2 (COX-2) inhibitor celecoxib to kill Staphylococcus aureus and MRSA with modest potency. We hypothesize that the anti-Staphylococcus activity of celecoxib could be pharmacologically exploited to develop novel anti-MRSA agents with a distinct mechanism. Examination of an in-house, celecoxib-based focused compound library in conjunction with structural modifications led to the identification of compound 46 as the lead agent with high antibacterial potency against a panel of Staphylococcus pathogens and different strains of MRSA. Moreover, this killing effect is bacteria-specific, as human cancer cells are resistant to 46. In addition, a single intraperitoneal administration of compound 46 at 30 mg/kg improved the survival of MRSA-infected C57BL/6 mice. In light of its high potency in eradicating MRSA in vitro and its in vivo activity, compound 46 and its analogues warrant continued preclinical development as a potential therapeutic intervention against MRSA. (C) 2012 Elsevier Ltd. All rights reserved.